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CARVYKTI® (ciltacabtagene autoleucel)

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CARVYKTI - CARTITUDE-4 (MMY3002) Study

Last Updated: 12/18/2024

SUMMARY

  • CARTITUDE-4 (MMY3002) is a phase 3, randomized, open-label study evaluating the efficacy and safety of CARVYKTI versus standard care (physician's choice of pomalidomide, bortezomib, and dexamethasone [PVd] or DARZALEX FASPRO® [daratumumab and hyaluronidase], pomalidomide, and dexamethasone [DPd]) in adult patients with lenalidomide-refractory multiple myeloma (MM) after 1-3 prior line(s) of therapy (LOT).1,2
  • Primary Analysis (15.9 months):
  • Interim Analysis (33.6 months):
    • At a median follow-up of 33.6 months (range, 0.1-45.0) in the ITT population, CARVYKTI significantly improved overall survival (OS) vs standard care (HR, 0.55; 95% CI, 0.39-0.79; P=0.0009). The 30-month OS rate in the CARVYKTI and standard care arms was 76.4% and 63.8%, respectively.6
    • CARVYKTI significantly prolonged PFS vs standard care (HR, 0.29; 95% CI,
      0.22-0.39; P<0.0001). The 30-month PFS rate in the CARVYKTI and standard care arms was 59.4% and 25.7%, respectively.6
    • Overall minimal residual disease (MRD)-negativity in ITT population at the 10-5 threshold was achieved in 62.0% of CARVYKTI patients and in 18.5% of standard care patients (odds ratio [OR]: 7.6; P<0.0001). MRD-negativity at the 10-6 threshold was achieved in 57.2% of CARVYKTI patients and in 9.0% of standard care patients (OR: 14.9; P<0.0001).6,7 
      • CARVYKTI significantly increased the overall MRD-negative complete response or better (≥CR) at the 10-5 threshold compared to standard care in patients evaluable for MRD (82.1% vs 25.2%; OR, 12.3; P<0.0001).7
      • CARVYKTI increased the overall sustained (≥12 months) MRD-negative ≥CR at the 10-5 threshold compared to standard care in patients evaluable for MRD (51.7% vs 9.7%).7
    • In both the CARVYKTI arm and standard care arm, approximately 97% of patients experienced grade 3/4 treatment-emergent AEs (TEAEs).6 There were no new cases of cranial nerve palsy (CNP) or movement and neurocognitive TEAEs (MNTs) reported for the CARVYKTI arm since the previous report.1,6
    • Infections, cause of death, and second primary malignancy (SPM) were evaluated for both the CARVYKTI and standard care arms and are presented in Table: CARTITUDE-4: Infections, Cause of Death, and SPM - Interim Analysis.6
  • Subgroup analyses were conducted from the CARTITUDE-4 study that evaluated the following:
    • PFS in subgroups of patients with high-risk disease features in both the ITT and as-treated populations.8
    • Efficacy and safety outcomes in patients who received 1 prior LOT, including the subset of patients with functionally high-risk MM.9
    • Efficacy of CARVYKTI compared to standard care in patients with high-risk cytogenetic abnormalities.10
  • Patient-reported outcomes (PROs) and time to next antimyeloma therapy were evaluated at a median follow-up of 33.6 months (range, 0.1-45.0) in both the CARVYKTI and standard care arms.11
  • Other relevant company sponsored literature has been identified in addition to the data summarized above:
    • A post hoc analysis evaluated the efficacy of CARVYKTI by the response to bridging therapy in patients who received CARVYKTI as study treatment in CARTITUDE-4. At a median follow-up of 15.9 months, the median PFS was NR (95% CI, not estimable [NE]-NE) in patients with ≥25% tumor burden reduction vs 19.2 months (95% CI, 15.8-NE) in patients with <25% decrease in tumor burden (HR, 0.32; 95% CI,
      0.16-0.66).12
    • Infections and immune reconstitution in CARTITUDE-4 were characterized at a median follow-up of 21.5 months. Treatment-emergent (TE) infections of any grade were reported in 61.5% of patients in the CARVYKTI arm (n=128) and in 75.5% of patients in the standard care arm (n=157). Grade ≥3 TE infections were reported in 27.4% of patients in the CARVYKTI arm (n=57) and 26.9% of patients in the standard care arm (n=56). Grade ≥3 events decreased in the CARVYKTI arm after month 6, with a more gradual decrease over time observed in the standard care arm.13

PRODUCT LABELING

CLINICAL DATA - cartitude-4

CARTITUDE-4 (MMY3002; clinicaltrials.gov identifier: NCT04181827) is an ongoing, phase 3, randomized, open-label study evaluating the efficacy and safety of CARVYKTI versus standard care (physician's choice of PVd or DPd) in adult patients with lenalidomide-refractory MM after 1-3 prior LOT.1

Study Design/Methods

  • The study design is shown in Figure: CARTITUDE-4 Study Design.
  • Patients were randomized 1:1 into one of two arms to receive the following treatments:
    • Standard care arm (PVd or DPd)
      • 21-day cycles of PVd which included: pomalidomide 4 mg orally (PO) on days 1 to 14 in each cycle; bortezomib 1.3 mg/m2 subcutaneously (SC) on days 1, 4, 8, and 11 (cycles 1 to 8) and on days 1 and 8 (cycle 9 onwards); dexamethasone 20 mg (10 mg/day for participants >75 years of age) PO on days 1, 2, 4, 5, 8, 9, 11, and 12 (cycles 1 to 8) and on days 1, 2, 8, and 9 (cycle 9 onwards).4,14
      • Or 28-day cycles of DPd which included: DARZALEX FASPRO 1800 mg SC weekly on days 1, 8, 15, and 22 (cycles 1 and 2), every 2 weeks on days 1 and
        15 (cycles 3 to 6) and every 4 weeks on day 1 (Cycle 7 onwards); pomalidomide 4 mg PO on days 1 to 21 (cycle 1 onwards); dexamethasone 40 mg (20 mg weekly for participants >75 years of age) PO or intravenous (IV) weekly on days 1, 8, 15, and 22 or split over 2 days (cycle 1 onwards).4,14
      • Treatment with PVd or DPd continued until disease progression, death, intolerable toxicity, withdrawal of consent, or end of the study, whichever occurred earlier.1,14
      • Per protocol, if patients had disease progression after standard treatment, crossover from the standard care arm to the CARVYKTI arm was not permitted.1
    • CARVYKTI arm
      • After undergoing apheresis, patients received ≥1 cycle of bridging therapy (physicians’ choice) with PVd or DPd (number of cycles was based on clinical status and CARVYKTI manufacturing time).1
        • PVd as bridging therapy was administered as 21-day cycles of pomalidomide 4 mg PO daily for 14 days; bortezomib 1.3 mg/m2 SC on bridging days 1, 4, 8 and 11 and dexamethasone 20 mg PO on bridging days 1, 2, 4, 5, 8, 9, 11, and 12.1,4
        • DPd as bridging therapy was administered as 28-day cycles of DARZALEX FASPRO 1800 mg SC weekly on days 1, 8, 15, and 22; pomalidomide 4 mg PO for 21 days and dexamethasone 40 mg PO or IV on bridging days 1, 8, 15, and 22 or split over 2 days (two-20 mg doses).1,4
      • A lymphodepletion/conditioning regimen of cyclophosphamide 300 mg/m2 and fludarabine 30 mg/m2 was administered daily for 3 days.1
      • Patients received a single infusion of CARVYKTI on day 1 at a target dose of 0.75x106 CAR+ T cells/kg 5-7 days after the start of lymphodepletion.1
      • Patients who had confirmed disease progression during bridging therapy or lymphodepletion were assessed as having a progression event. Subsequent therapy with CARVYKTI could be administered at investigator discretion.1
  • MRD was assessed from cycle 1 day 1 for the standard care arm and from CARVYKTI infusion for the CARVYKTI arm. Evaluation for sustained MRD required ≥2 evaluable samples, at least 12 weeks apart, with no progression, death, or next therapy in that interval.7
    • Overall MRD-negative CR rate was defined as the proportion of patients achieving MRD-negativity within 3 months of achieving ≥CR post-randomization and prior to disease progression or initiation of subsequent antimyeloma therapy.7
    • Sustained MRD-negative ≥CR was defined as achievement of MRD-negative status and CR in succession, confirmed at least 1 year apart with no MRD-positive status, disease progression, or subsequent antimyeloma therapy.7

CARTITUDE-4 Study Design1,14

Abbreviations: BCMA, B-cell maturation antigen; CAR, chimeric antigen receptor; cilta-cel, ciltacabtagene autoleucel; CR, complete response; Cy, cyclophosphamide; DPd, daratumumab, pomalidomide, and dexamethasone; ECOG, Eastern Cooperative Oncology Group; Flu, fludarabine; IMWG, International Myeloma Working Group; ISS, International Staging System; IV, intravenous; MM, multiple myeloma; MRD, minimal residual disease; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PI, proteasome inhibitor; PK, pharmacokinetics; PRO, patient-reported outcome; PVd, pomalidomide, bortezomib, and dexamethasone.
aRandomization was stratified by choice of PVd vs DPd, ISS stage at screening (I vs II vs III), and number of prior lines of therapy (1 vs 2-3).
bTreatment with PVd or DPd continued until disease progression, death, intolerable toxicity, withdrawal of consent, or end of the study, whichever occurred earlier.
cSecondary outcomes were sequentially tested at each prespecified significance level, including (in order) rates of CR or better, ORR, MRD negativity, OS, and time to patient-reported symptom worsening as assessed by the MM Symptom and Impact Questionnaire.

Results

Patient Demographics and Disease/Treatment Characteristics

  • Overall, 419 patients were randomized to receive CARVYKTI (n=208) or standard care (n=211; DPd [n=183] or PVd [n=28]).1
    • All 208 patients randomized to the CARVYKTI arm received bridging therapy with either DPd (n=182) or PVd (n=26). A total of 176 patients (84.6%) received CARVYKTI as study treatment (as-treated population). In the as-treated population, 21.6% of patients received 1 bridging therapy cycle, 58.5% of patients received 2 bridging therapy cycles, and 19.9% of patients received 3-6 bridging therapy cycles.1,2
      • Prior to receipt of CARVYKTI, 32 patients discontinued study treatment mainly due to disease progression (n=30) or death (n=2) during bridging therapy or lymphodepletion. Of these, 20 patients received subsequent therapy with CARVYKTI. No patients discontinued treatment due to a manufacturing failure. The median time from apheresis material receipt to product release was 44 days (range, 25-127) and the median time from first apheresis to CARVYKTI infusion was 79 days (range, 45-246).1,4
    • A total of 208 patients (98.6%) were dosed with standard care.1
      • Treatment discontinuation was reported in 131 standard care patients (63.0%), mostly due to disease progression (56.3%).1
  • Patient details and a summary of prior therapies for the ITT population are presented in Table: CARTITUDE-4: Baseline Demographics and Disease Characteristics (ITT Population) and Table: CARTITUDE-4: Treatment History at Baseline (ITT Population).
    • The median prior LOT in both the CARVYKTI and standard care arms were 2 (range, 1-3).3
  • Patient details and a summary of prior therapies for the as-treated population are presented in Table: CARTITUDE-4: Baseline Demographics and Disease Characteristics (As-Treated Population) and Table: CARTITUDE-4: Treatment History at Baseline (As-Treated Population).
  • The median CARVYKTI dose administered was 0.71x106 CAR+ T cells/kg and patients in the standard care arm received a median of 12 treatment cycles (range, 1-28).1

CARTITUDE-4: Baseline Demographics and Disease Characteristics (ITT Population)1,8
Characteristic
CARVYKTI
(n=208)
Standard Care
(n=211)
Age, median (range), years
61.5 (27-78)
61.0 (35-80)
Male, n (%)
116 (55.8)
124 (58.8)
Race, n (%)
   White
157 (75.5)
157 (74.4)
   Blacka
6 (2.9)
7 (3.3)
   Asian
16 (7.7)
20 (9.5)
ECOG PS, n (%)
   0
114 (54.8)
121 (57.3)
   1
93 (44.7)
89 (42.2)
   2b
1 (0.5)
1 (0.5)
ISS stage, n (%)
   I
136 (65.4)
132 (62.6)
   II
60 (28.8)
65 (30.8)
   III
12 (5.8)
14 (6.6)
Median years since diagnosis, (range)
3.0 (0.3-18.1)
3.4 (0.4-22.1)
Presence of soft-tissue plasmacytomasc, n (%)
44 (21.2)
35 (16.6)
Bone marrow plasma cells ≥60%d, n (%)
42 (20.4)
43 (20.7)
Cytogenetic riske, n (%)
   Standard risk
69 (33.3)
70 (33.3)
   High risk
123 (59.4)
132 (62.9)
      gain/amp(1q)
89 (43.0)
107 (51.0)
      del (17p)
49 (23.7)
43 (20.5)
      t(4;14)
30 (14.5)
30 (14.3)
      t(14;16)
3 (1.4)
7 (3.3)
      ≥2 high-risk abnormalities
43 (20.8)
49 (23.3)
      del(17p), t(4;14), or t(14;16)
73 (35.3)
69 (32.9)
   Unknown
15 (7.2)
8 (3.8)
Tumor BCMA expression ≥50%, n (%)
141 (67.8)
138 (65.4)
Abbreviations: BCMA, B-cell maturation antigen; ECOG PS, Eastern Cooperative Oncology Group performance status; ISS, International Staging System; ITT, intention-to-treat.
aAmong patients enrolled in the United States, 9 patients (14.1%) were Black.
bLatest non-missing ECOG PS on or prior to apheresis/cycle 1 day 1 was used. All patients met the inclusion criteria of ECOG PS of 0 or 1 prior to randomization.
cIncluding extramedullary and bone‑based plasmacytomas with measurable soft tissue component.
dIn 206 (CARVYKTI arm) and 208 (standard care arm) patients; maximum value from bone marrow biopsy and bone marrow aspirate is selected if both results are available.
eIn 207 (CARVYKTI arm) and 210 (standard care arm) patients.

CARTITUDE-4: Treatment History at Baseline (ITT Population)1,3,8
Treatment, n (%)
CARVYKTI
(n=208)
Standard Care
(n=211)
Prior lines of therapy
   1
68 (32.7)
68 (32.2)
   2
83 (39.9)
87 (41.2)
   3
57 (27.4)
56 (26.5)
Prior immunomodulatory drugs
208 (100.0)
211 (100.0)
   Lenalidomide
208 (100.0)
211 (100.0)
   Pomalidomide
8 (3.8)
10 (4.7)
Prior anti-CD38 antibody
53 (25.5)
55 (26.1)
   Daratumumab
51 (24.5)
54 (25.6)
   Isatuximab
2 (1.0)
2 (0.9)
Prior proteasome inhibitors
208 (100.0)
211 (100.0)
   Bortezomib
203 (97.6)
205 (97.2)
   Carfilzomib
77 (37.0)
66 (31.3)
   Ixazomib
21 (10.1)
21 (10.0)
Triple-class exposeda
53 (25.5)
55 (26.1)
Penta-drug exposedb
14 (6.7)
10 (4.7)
Refractory status
   Lenalidomide
208 (100.0)
211 (100.0)
   Bortezomib    
55 (26.4)
48 (22.7)
   Carfilzomib
51 (24.5)
45 (21.3)
   Any anti-CD38 antibody
50 (24.0)
46 (21.8)
   Daratumumab
48 (23.1)
45 (21.3)
   Ixazomib
15 (7.2)
17 (8.1)
   Pomalidomide
8 (3.8)
9 (4.3)
   Triple-class refractorya
30 (14.4)
33 (15.6)
   Penta-drug refractoryb
2 (1.0)
1 (0.5)
Abbreviations: CD, cluster of differentiation; ITT, intention-to-treat. aIncluding 1 proteasome inhibitor, 1 immunomodulatory drug, and 1 anti-CD38 antibody.
bIncluding ≥2 proteasome inhibitors, ≥2 immunomodulatory drugs, and 1 anti-CD38 antibody.

CARTITUDE-4: Baseline Demographics and Disease Characteristics (As-Treated Population)2,8
Characteristic
As-Treated Population
(n=176)
Age, median (range), years
61 (27-78)
Male, n (%)
101 (57.4)
Race, n (%)
   White
136 (77.3)
   Black or African American
6 (3.4)
   Asian
15 (8.5)
   Not reported
19 (10.8)
ECOG PS, n (%)
   0
103 (58.5)
   1
73 (41.5)
ISS stage, n (%)
   I
121 (68.8)
   II
45 (25.6)
   III
10 (5.7)
Bone marrow plasma cells ≥60%a, n (%)
33 (18.9)
Presence of soft tissue plasmacytomasb, n (%)
   Yes
30 (17.0)
   No
146 (83.0)
Cytogenetic riskc, n %
   Standard risk
59 (33.7)
   High-riskd
105 (60.0)
      gain/amp(1q)
77 (44.0)
      del (17p)
39 (22.3)
      t(4;14)
23 (13.1)
      t(14;16)
3 (1.7)
      del(17p), t(14;16), or t(4;14)
59 (33.7)
      ≥2 high-risk abnormalities
34 (19.4)
   Unknown risk
11 (6.3)
Abbreviations: ECOG PS, Eastern Cooperative Oncology Group performance status; ISS, International Staging System.
a Maximum value from bone marrow biopsy and bone marrow aspirate selected if both results are available.
bSoft-tissue plasmacytomas included extramedullary and bone-based plasmacytomas with a measurable soft tissue component.
c Cytogenetics data for the as-treated were available for 175 of 176 patients.
d Any of the following features: del(17p), t(14;16), t(4;14), or gain/amp(1q).

CARTITUDE-4: Treatment History at Baseline (As-Treated Population)2,8
Characteristic
As-Treated Population
(n=176)
Number of prior LOT, n %
   1
60 (34.1)
   2
66 (37.5)
   3
50 (28.4)
Treatment refractoriness
   Triple-class refractorya, n %
20 (11.4)
   Not triple-class refractory
156 (88.6)
Treatment history
   Prior daratumumab exposed
36 (20.5)
   Prior triple-class exposeda
37 (21.0)
Abbreviations: CD, cluster of differentiation; LOT, line of therapy.
aIncluding 1 proteasome inhibitor, 1 immunomodulatory drug, and 1 anti-CD38 monoclonal antibody.

Primary Analysis (15.9 months)

Efficacy

ITT Population
  • At the data cut-off date of November 1, 2022, 143 CARVYKTI patients were ongoing in the post-treatment phase and 77 patients were ongoing on standard care therapy.1
  • Efficacy was evaluated in the ITT population (all randomized patients).1 Efficacy outcomes in this population are presented in Table: CARTITUDE-4: Efficacy - Response (ITT Population - Primary Analysis).
    • CARVYKTI significantly prolonged PFS vs standard care (HR, 0.26; 95% CI, 0.18-0.38; P<0.001); the median PFS was NR in the CARVYKTI arm and was 11.8 months (95% CI, 9.7-13.8) in the standard care arm. The
      12-month PFS rates (95% CI) for the CARVYKTI arm and standard care arms were 75.9% (69.4-81.1) and 48.6% (41.5-55.3), respectively.1
      • In an unweighted sensitivity analysis, CARVYKTI improved PFS compared with standard care (HR, 0.40; 95% CI, 0.29-0.55; P<0.0001).4
      • During the first 8 weeks after randomization, PFS events (disease progression or death) were reported in the CARVYKTI arm (22 patients; all events occurred before CARVYKTI infusion while patients were on bridging therapy; same treatment in both arms) and the standard care arm (8 patients). During this bridging therapy period, relative doses of pomalidomide and bortezomib were approximately 14% lower in the CARVYKTI arm vs the standard care arm.1
    • MRD-negativity in the ITT population at any time up to data cut-off during the study was achieved in 60.6% of CARVYKTI patients and 15.6% of standard care patients, respectively; risk ratio of 2.2 (95% CI,
      1.8-2.6; P<0.001) and an OR of 8.7 (95% CI, 5.4-13.9).1
      • MRD evaluable samples were available in 144 patients in the CARVYKTI arm and in 101 patients in the standard care arm. Among these patients, MRD-negativity was achieved in 87.5% of CARVYKTI patients (n=126) and 32.7% of standard care patients (n=33).1
    • OS was immature; a total of 39 deaths were reported in the CARVYKTI arm and 46 deaths were reported in the standard care arm (HR, 0.78; 95% CI, 0.5-1.2; P=0.26). At 12 months, an estimated 84.1% of CARVYKTI patients were alive vs 83.6% of standard care patients.1,3
    • Median times to symptom worsening (95% CI) were 23.7 months (22.1-NE) and 18.9 months (16.8-NE) in the CARVYKTI and standard care arms, respectively (HR, 0.42 [95% CI, 0.26-0.68]).1
As-treated Population
  • Efficacy outcomes for patients who received CARVYKTI as study treatment are detailed in Table: CARTITUDE-4: Efficacy - Response (As-Treated Population - Primary Analysis).
    • The overall response rate was 99.4%, with 86.4% of patients achieving a best response of ≥CR. Details on the best overall response over time are displayed in Figure: CARTITUDE-4: Responses Over Time (As-Treated Population - Primary Analysis).2
    • The median duration of response and median PFS were NR.2
    • In MRD evaluable patients (n=144), improved PFS from infusion was observed in patients with MRD-negative ≥CR vs patients who remained MRD-positive and/or had <CR (P=0.0196).2
      • In MRD evaluable patients with MRD-negative ≥CR: median PFS was NR (95% CI, 20.63-NE) and 12-month PFS rate was 88.9% (95% CI, 80.0-93.8).2
      • In patients who remained MRD-positive and/or had <CR: median PFS was NR (95% CI, 11.33-NE) and 12-month PFS rate was 70.9% (95% CI, 48.8-84.8).2

CARTITUDE-4: Efficacy - Response (ITT Population - Primary Analysis)1,3
CARVYKTI
(n=208)
Standard Care
(n=211)
Odds Ratio
(95% CI)a
ORRb, n (%)
176 (84.6)
142 (67.3)
3.0 (1.8-5.0)
   sCR
121 (58.2)
32 (15.2)
-
   CR
31 (14.9)
14 (6.6)
-
   VGPR
17 (8.2)
50 (23.7)
-
   PR
7 (3.4)
46 (21.8)
-
SD
13 (6.2)
47 (22.3)
-
PD
17 (8.2)
6 (2.8)
Not evaluable
1 (0.5)
5 (2.4)
-
≥CR
152 (73.1)
46 (21.8)
10.3 (6.5-16.4)
≥VGPR
169 (81.2)
96 (45.5)
5.9 (3.7-9.4)
MRD-negativityc, n (%)
126 (60.6)
33 (15.6)
8.7 (5.4-13.9)
Median time to first response, months (range)
2.1 (0.9-11.1)
1.2 (0.6-10.7)
-
Median time to best response, months (range)
6.4 (1.1-18.6)
3.1 (0.8-20.6)
-
Median DOR, months (95% CI)
NR
16.6 (12.9-NE)
-
12-month DOR, % (95% CI)
84.7 (78.1-89.4)
63.0 (54.2-70.6)
-
Median PFS, months (95% CI)
NR (22.8-NE)
11.8 (9.7-13.8)
-
12-month PFS, % (95% CI)
75.9 (69.4-81.1)
48.6 (41.5-55.3)
-
Abbreviations: CI, confidence interval; CR, complete response; DOR, duration of response; ITT, intention-to-treat; MRD, minimal residual disease; NE, not estimable; NR, not reached; ORR, overall response rate; PD, progressive disease; PFS, progression-free survival; PR, partial response; sCR, stringent complete response; SD, stable disease; VGPR, very good partial response.
aMantel-Haenszel estimate of the common odds ratio for stratified tables is used. An odds ratio >1 indicates an advantage for CARVYKTI.
bAchieved at any time up to data cut-off during the study. Includes patients who achieved ≥PR.
cAt 10-5 threshold, assessed by next-generation sequencing. Data regarding MRD was available for 126/144 CARVYKTI patients (87.5%) and for 33/101 standard care patients (32.7%).

CARTITUDE-4: Efficacy - Response (As-Treated Population - Primary Analysis)2-4
CARVYKTI
(n=176)a
ORR after randomizationb, n (%)
175 (99.4)
   sCR
121 (68.8)
   CR
31 (17.6)
   VGPR
17 (9.7)
   PR
6 (3.4)
SD
1 (0.6)
PD
0
≥CR
152 (86.4)
≥VGPR
169 (96.0)
MRD-negative after infusion, n (%)
126 (71.6)
   In MRD evaluablec, n/N (%)
126/144 (87.5)
   MRD-negative ≥CR, n/N (%)
111/144 (77.1)
Time to first response after randomization, months (range)
2.1 (0.9-11.1)
PFS rate 12 months after infusion, % (95% CI)
84.9 (78.2-89.7)
OS rate 12 months after infusion, % (95% CI)
91.9 (86.6-95.1)
Median time to best response, months (range)
6.5 (1.1-18.6)
Median DOR, months (95% CI)
NR
Abbreviations: CI, confidence interval; CR, complete response; DOR, duration of response; MRD, minimal residual disease; NR, not reached; ORR, overall response rate; OS, overall survival; PD, progressive disease; PFS, progression-free survival; PR, partial response; sCR, stringent complete response; SD, stable disease; VGPR, very good partial response.
aA total of 208 patients were randomized to the CARVYKTI arm; 176 patients (84.6%) received CARVYKTI as study treatment.
bIncludes patients who achieved ≥PR.
cPatients with a bone marrow sample evaluable at 10-5 threshold, assessed by next-generation sequencing.

CARTITUDE-4: Responses Over Timea,b (As-Treated Population - Primary Analysis)2

Abbreviations: CCO, clinical cut-off; CR, complete response; mFU, median follow-up; mo, month; ORR, overall response rate; PR, partial response; sCR, stringent complete response; VGPR, very good partial response.
aBest overall response by each time point post randomization and at CCO in the as-treated population (n=176).
bSum of best response rates may not be equal to ORR due to rounding.
cNo patients had ≥CR by month 1 after randomization.

Safety

  • AEs were evaluated in the safety population which included all patients who received any part of study treatment (n=208 in each of the CARVYKTI and standard care arms). CAR-T specific AEs were evaluated in patients who received CARVYKTI as study treatment (as-treated population; n=176).1
  • The most common (≥15% all grade) AEs are detailed in Table: CARTITUDE-4: Adverse Events (≥15% All Grade in Any Arm) - Primary Analysis.
  • The incidence of prolonged (>60 days) grade 3/4 cytopenias in patients who received CARVYKTI as study treatment (n=176) was 10.8% for thrombocytopenia, 10.2% for lymphopenia, 10.2% for neutropenia and 1.1% for anemia.4
  • Serious AEs were reported in 44.2% of patients (n=92) in the CARVYKTI arm and 38.9% of patients (n=81) in the standard care arm. In the standard care arm, AEs caused treatment discontinuation in 3 patients (1.4%) and caused cycle delays in 115 patients (55.3%).1
  • SPMs were reported in 4.3% (n=9) and 6.7% (n=14) of patients in the CARVYKTI arm and standard care arm, respectively.1 Complete details are provided in Table: CARTITUDE-4: Second Primary Malignancies - Primary Analysis.
  • Infections of any grade occurred in 62.0% of CARVYKTI patients (n=129) and in 71.2% of standard care patients (n=148). Coronavirus disease 2019 (COVID-19) infection was reported in 13.9% of CARVYKTI patients (n=29) and in 26.4% of standard care patients (n=55). Grade 3/4 COVID-19 occurred in 2.9% of CARVYKTI patients (n=6) and in 5.8% of standard care patients (n=12).1
  • Based on AE reporting and laboratory results, hypogammaglobulinemia was reported in 90.9% of patients in the CARVYKTI arm and 71.6% of patients in the standard care arm. On the basis of AE reporting alone, the corresponding incidence of hypogammaglobulinemia was 42.3% and 6.2%, respectively. IV immunoglobulin was administered in 65.9% of CARVYKTI patients and 12.5% of standard care patients.1
  • In the safety population, a total of 39 CARVYKTI patients and 46 standard care patients died from any cause (one patient in the standard care group died prior to treatment).1 Complete details can be found in Table: CARTITUDE-4: Deaths - Primary Analysis.
Cytokine Release Syndrome
  • The incidence, timing/duration and management of cytokine release syndrome (CRS) in patients treated with CARVYKTI as study treatment are detailed in Table: CARTITUDE-4: CRS - Primary Analysis.
    • CRS occurred in 76.1% of patients (n=134). The median time to onset of CRS was 8 days (range, 1-23) with a median duration of 3 days (range, 1-17). CRS resolved in all patients.1-4
Neurotoxicity
  • The incidence of neurotoxicities in patients treated with CARVYKTI as study treatment is detailed in Table: CARTITUDE-4: Neurotoxicities - Primary Analysis.
    • CAR-T related neurotoxicities of any grade occurred in 20.5% of patients (n=36).1,2
    • A total of 8 patients (4.5%) experienced immune effector cell-associated neurotoxicity syndrome (ICANS); all were grade 1/2. The median time to onset was 10 days with a median duration of 2 days (range, 1-6). Supportive treatments for ICANS were given to 4 patients (corticosteroids, n=4; tocilizumab, n=2). ICANS resolved in all patients.1-4
    • Other neurotoxic events of any grade were reported in 30 patients (17%), with 4 of these patients (2.3%) having grade 3/4 other neurotoxicities.1,3,4
    • CNPs of any grade were reported in 16 patients (9.1%). All cases involved cranial nerve VII (n=16); 2 cases involved a second cranial nerve (cranial nerves III and V; n=1 each) The median onset was 21 days (range, 17-60) post CARVYKTI infusion with a median duration of 77 days (range, 15-262). Corticosteroids were administered to 14 patients as supportive treatment. At data cut-off, 14 of 16 patients had recovered. No clear risk factors for CNPs have been identified, and the mechanism is not understood.1,3-5
    • Peripheral neuropathies of any grade were reported in 5 patients (2.8%). The median onset was 63 days (range, 31-127) with a median duration of 201 days (range, 107-503). At data cut-off, 3 of 5 patients had recovered.1,2,4
  • One patient (male) experienced a grade 1 MNT beginning on day 85 post infusion. The patient experienced balance disorder, bradykinesia, extrapyramidal disorder, gait disturbance, micrographia, parkinsonism, psychomotor retardation, and reduced facial expression. Patient was treated with levodopa and carbidopa monohydrate; event was ongoing at data cut-off.1,4
    • Patient was refractory to DPd bridging therapy and had grade 2 CRS (risk factors for MNTs).1,4
  • There were no fatal neurotoxicities.1,2

CARTITUDE-4: AEs (≥15% All Grade in Any Arm) - Primary Analysis1
Eventa, n (%)
CARVYKTI
(n=208)
Standard Care
(n=208)
All Grade
Grade 3/4
All Grade
Grade 3/4
Any AE, n (%)
208 (100)
201 (96.6)
208 (100)
196 (94.2)
Hematologic
197 (94.7)
196 (94.2)
185 (88.9)
179 (86.1)
   Neutropenia
187 (89.9)
187 (89.9)
177 (85.1)
171 (82.2)
   Thrombocytopenia
113 (54.3)
86 (41.3)
65 (31.2)
39 (18.8)
   Anemia
113 (54.3)
74 (35.6)
54 (26.0)
30 (14.4)
   Lymphopenia
46 (22.1)
43 (20.7)
29 (13.9)
25 (12.0)
Nonhematologic
   Infections
129 (62.0)
56 (26.9)
148 (71.2)
51 (24.5)
      Upper respiratory tract infectionsb
39 (18.8)
4 (1.9)
54 (26.0)
4 (1.9)
      COVID-19c
29 (13.9)
6 (2.9)
55 (26.4)
12 (5.8)
      Lower respiratory tract/lung infectionsd
19 (9.1)
9 (4.3)
36 (17.3)
8 (3.8)
   Other nonhematologic
      Nausea
101 (48.6)
0
38 (18.3)
2 (1.0)
      Hypogammaglobulinemia
88 (42.3)
15 (7.2)
13 (6.2)
1 (0.5)
      Diarrhea
70 (33.7)
8 (3.8)
56 (26.9)
5 (2.4)
      Fatigue
60 (28.8)
4 (1.9)
68 (32.7)
2 (1.0)
      Headache
55 (26.4)
0
27 (13.0)
0
      Constipation
49 (23.6)
1 (0.5)
44 (21.2)
2 (1.0)
      Hypokalemia
39 (18.8)
8 (3.8)
14 (6.7)
3 (1.4)
      Asthenia
36 (17.3)
1 (0.5)
34 (16.3)
5 (2.4)
      Peripheral edema
35 (16.8)
0
24 (11.5)
2 (1.0)
      Decreased appetite
34 (16.3)
2 (1.0)
11 (5.3)
0
      Peripheral sensory neuropathy
33 (15.9)
0
38 (18.3)
1 (0.5)
      Back pain
33 (15.9)
2 (1.0)
39 (18.8)
2 (1.0)
      Arthralgia
32 (15.4)
2 (1.0)
25 (12.0)
1 (0.5)
      Pyrexia
32 (15.4)
0
32 (15.4)
2 (1.0)
      Dyspnea
28 (13.5)
1 (0.5)
41 (19.7)
1 (0.5)
      Insomnia
23 (11.1)
2 (1.0)
52 (25.0)
6 (2.9)
Abbreviations: AE, adverse event; COVID-19, coronavirus disease 2019.
aAEs were graded per National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0.
bIncludes preferred terms upper respiratory tract infection, nasopharyngitis, sinusitis, rhinitis, tonsillitis, pharyngitis, laryngitis, and pharyngotonsillitis.
cIncludes preferred terms COVID-19, COVID-19 pneumonia, and asymptomatic COVID-19. In addition, there were 7 (CARVYKTI) and 1 (standard-of-care) grade 5 events.
dIncludes preferred terms lower respiratory tract infection, pneumonia, and bronchitis.

CARTITUDE-4: Second Primary Malignancies - Primary Analysis4
CARVYKTI
(n=208)
Standard Care
(n=208)
Second primary malignancy, n (%)
9 (4.3)
14 (6.7)
Cutaneous/non-invasive malignancies
5 (2.4)
10 (4.8)
   Basal cell carcinoma
2 (1.0)
7 (3.4)
   Bowen disease
0
2 (1.0)
   Lip squamous cell carcinoma
0
1 (0.5)
   Malignant melanoma
1 (0.5)
0
   Malignant melanoma in situ
1 (0.5)
0
   Squamous cell carcinoma of skin
2 (1.0)
4 (1.9)
Hematologic malignancies
3 (1.4)
0
   Acute myeloid leukemia
1 (0.5)
0
   Myelodysplastic syndrome
1 (0.5)a
0
   Peripheral T-cell lymphoma
1 (0.5)
0
Noncutaneous/invasive malignancies
1 (0.5)
4 (1.9)
   Angiosarcoma
1 (0.5)
0
   Invasive lobular breast carcinoma
0
1 (0.5)
   Pleomorphic malignant fibrous histiocytoma
0
1 (0.5)
   Renal cell carcinoma
0
1 (0.5)
   Tonsil cancer
0
1 (0.5)
aPatient had essential thrombocythemia at study entry.

CARTITUDE-4: Deaths - Primary Analysis4

CARVYKTI
(n=208)
Standard Care
(n=208)
Deaths, n (%)
39 (18.8)
46 (22.1)
   Progressive disease
14 (6.7)a
30 (14.4)
   Non-treatment emergent AEb
15 (7.2)
11 (5.3)
   Treatment-emergent AE
10 (4.8)c
5 (2.4)
   COVID-19 pneumoniac
7 (3.4)
1 (0.5)
      Neutropenic sepsis
1 (0.5)
0
      Pneumonia
1 (0.5)
0
      Progressive multifocal leukoencephalopathy
0
1 (0.5)
      Respiratory tract infection
0
1 (0.5)
      Septic shock
0
1 (0.5)
      Respiratory failure
1 (0.5)d
0
      Pulmonary embolism
0
1 (0.5)
Abbreviations: AE, adverse event; COVID-19, coronavirus disease 2019; DPd, DARZALEX FASPRO, pomalidomide, and dexamethasone; PVd, pomalidomide, bortezomib, and dexamethasone. aA total of 8 of these patients did not receive CARVYKTI.
bAEs in the CARVYKTI arm were considered non-treatment emergent if they were not considered related to study treatment, and they occurred either >112 days after CARVYKTI or during subsequent therapy; for the standard care arm, AEs were considered non-treatment emergent if they were not considered related to study treatment (DPd or PVd), and they occurred more than 30 days after the last dose of study treatment or after the start of subsequent therapy, whichever came first.
cIn total, 4 CARVYKTI patients received 2 or 3 COVID-19 vaccinations prior to receiving CARVYKTI; 3 patients received no vaccines prior to CARVYKTI. 2 of 7 patients received 1 dose of COVID-19 vaccination after CARVYKTI. All patients had partial response or better to study treatment and did not progress prior to COVID-19 infection.dOccurred before CARVYKTI infusion.

CARTITUDE-4: CRS - Primary Analysis2,4

Total (n=176a)
Patients with a CRS event (all grade)b, n (%)
134 (76.1)
   Grade 1
93 (52.8)
   Grade 2
39 (22.2)
   Grade 3/4
2 (1.1)
Median time to onset of CRSc, days (range)
8 (1-23)
Median duration of CRS, days (range)
3 (1-17)
Supportive treatments, n
131
   Tocilizumab
71
   Oxygen therapy
17
   Corticosteroids
8
   Vasopressor
2
Abbreviation: CRS, cytokine release syndrome.
aAnalyzed in the patients who received CARVYKTI as study treatment.
bCRS was graded according to the American Society for Transplantation and Cellular Therapy criteria.
cTime to onset from CARVYKTI infusion.

CARTITUDE-4: Neurotoxicities - Primary Analysis1-5
Total (n=176a)
Patients with CAR-T related neurotoxicity, n (%)
36b (20.5)
   Grade 1/2, n
31
   Grade 3/4, n
5 (2.8)
ICANSc, n (%)
8 (4.5)
   Grade 1
6 (3.4)
   Grade 2
2 (1.1)d
   Grade 3
0
   Grade 4
0
   Grade 5
0
Other neurotoxicitiese, n (%)
30 (17.0)
   Grade 3/4f
4 (2.3)
   Grade 5
0
Cranial nerve palsyg, n (%)
16 (9.1)h
      Grade 2
14 (8.0)
      Grade 3/4
2 (1.1)
   Peripheral neuropathy, n (%)
5 (2.8)
      Grade 1
2 (1.1)
      Grade 2
2 (1.1)
      Grade 3/4
1 (0.6)
   MNT, n (%)
1 (0.6)
      Grade 1
1 (0.6)
Abbreviations: AE, adverse event; CAR, chimeric antigen receptor; ICANS, immune effector cell-associated neurotoxicity syndrome; MNT, movement and neurocognitive treatment-emergent adverse event.
aAnalyzed in the patients who received CARVYKTI as study treatment. b Several patients had both ICANS and “other” neurotoxicity.
cICANS was graded according to the American Society for Transplantation and Cellular Therapy criteria.
dGrade 3 syncope reported as a symptom of grade 2 ICANS.
eOther neurotoxicities include AEs reported as CAR-T cell neurotoxicity that are not ICANS or associated symptoms. These included (but were not limited to) MNTs, cranial nerve palsy, and peripheral neuropathy. Investigator-assessed non-ICANS neurotoxicity, were graded per National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0.
fOne case each of grade 3/4 neuralgia, third cranial nerve paralysis, polyneuropathy; and 1 patient with both trigeminal palsy and facial paralysis.
gSupportive measures included corticosteroids (14 patients). No clear risk factors for cranial nerve palsies have been identified and the mechanism is not understood.
hAll cases involved cranial nerve VII; 2 cases involved a second cranial nerve (cranial nerves III and V; each n=1).

Pharmacokinetics

  • CARVYKTI pharmacokinetics were assessed in the 176 patients who received CARVYKTI as study treatment.1
  • CAR+ T cell levels in blood were evaluated for pharmacokinetics using samples collected on day 1 pre infusion, and then evaluated on days 3, 7, 10, 14, 28, 56, 84, and 112, every 8 weeks for up to 1 year starting on day 140, and at disease progression or end of study.4
  • Cluster of differentiation (CD)3+ CAR+ cells in the blood peaked at a median of 13 days post infusion. The mean (±standard deviation) number of cells was 1451±6169 per mm3. Cells remained detectable for a median of 57 days (range, 13-631).1,15
  • The mean area under the curve in the first 28 days following CARVYKTI administration (AUC0-28d) of CD3+ CAR+ T cells in the blood was 11,710±56,994.5
  • Both CAR+ CD4 and CD8 T cells expanded after infusion (greater expansion was observed with CAR+ CD8 T cells). At time to peak peripheral expansion (Tmax), central memory CAR+ T cells were dominant in both CD4+ and CD8+ T-cell compartments.1
  • Serum B-cell maturation antigen (sBCMA) levels decreased in all patients, with a median time to undetectability of 56 days.5
T-cell and Cytokine Analysis in Cranial Nerve Impairment
  • In patients with and without CNP, the differentiation pattern of memory T cells was comparable in patients from apheresis to time of peak CAR+ T-cell expansion, with a dominant central memory phenotype in the CD4 and CD8 CAR+ compartments. Patients with CNP had significantly higher CAR+ T-cell peak expansion and exposure levels compared to patients without CNP (P<0.001 for both).5
  • Higher peak levels of interleukin (IL)-10 and higher exposure levels up to CNP onset of IL-10 and IL-2Rα were observed in patients with CNP vs those without CNP. There was a trend toward higher peak IL-6 and IL-2Rα and higher exposure levels of IL-6 in patients with CNP.5
  • There was no difference between groups in peak or exposure levels of interferon-gamma.5

Interim Analysis (33.6 months)

Efficacy

ITT Population
  • At the data cut-off date of May 1, 2024, 117 CARVYKTI patients were ongoing in the post-treatment phase and 43 patients were ongoing on standard care therapy.6
  • At a median follow-up of 33.6 months, (range, 0.1-45.0) CARVYKTI significantly improved OS and prolonged PFS and CR vs standard care.6,7
  • Data on OS, PFS, and MRD-negativity status across prespecified subgroups are detailed in Table: CARTITUDE-4: Efficacy - OS, PFS and MRD-Negativity Rates with CARVYKTI Compared to Standard Care Across Subgroups - Interim Analysis.6,7
  • Additional efficacy outcomes are presented in Table: CARTITUDE-4: Efficacy - Response Rates - Interim Analysis.6
  • Overall MRD-negativity in ITT population at the 10-5 threshold was achieved in 62.0% of CARVYKTI patients and in 18.5% of standard care patients (OR: 7.6; P<0.0001). Overall MRD-negativity at the 10-6 threshold was achieved in 57.2% of CARVYKTI patients and in 9.0% of standard care patients (OR: 14.9; P<0.0001).6,7
  • Among MRD evaluable patients (CARVYKTI arm, n=145 at 10-5 and n=139 at 10-6; standard care arm, n=103 at 10-5 and n=102 at 10-6), overall MRD-negativity at the 10-5 threshold was achieved in 89.0% of CARVYKTI patients and in 37.9% of standard care patients (OR: 13.3; P<0.0001). Overall MRD-negativity at the 10-6 threshold was achieved in 85.6% of CARVYKTI patients and in 18.6% of standard care patients (OR: 28.5; P<0.0001).6,7
    • In MRD evaluable patients, overall MRD-negative ≥CR at the 10-5 threshold was achieved in 82.1% of CARVYKTI patients and in 25.2% of standard care patients (OR: 12.3; P<0.0001). Sustained (≥12 months) MRD-negative ≥CR at the 10-5 threshold was achieved in 51.7% of CARVYKTI patients and in 9.7% of standard care patients.7
  • Overall, 69% of evaluable patients achieved MRD-negativity at the 10-5 threshold by day 56 (ITT 48%). This increased to 86% (ITT 60%) by 6 months post CARVYKTI infusion.6,7
  • In patients with sustained (≥12 months) MRD-negative ≥CR (n=75), the 30-month PFS rate was 93.2% and the 30-month OS rate was 97.3%.7
  • CARVYKTI significantly extended time to symptom worsening (Multiple Myeloma Symptom and Impact Questionnaire [MySIm-Q] total symptom scale; HR, 0.38; 95% CI, 0.24-0.61; P<0.0001).6

CARTITUDE-4: OS with CARVYKTI Compared to Standard Care - Interim Analysis6

Abbreviations: CI, confidence interval; cilta-cel, ciltacabtagene autoleucel; HR, Hazard ratio; OS, overall survival; SOC, standard care.
aLog-rank test. P-value, 0.0009, crossed the prespecified boundary of 0.0108 as implemented by the Kim-DeMets spending function with parameter=2.
bHazard ratio and 95% CI from a Cox proportional hazards model with treatment as the sole explanatory variable.

CARTITUDE-4: PFS with CARVYKTI Compared to Standard Care - Interim Analysis6

Abbreviations: CI, confidence interval; Cilta-cel, ciltacabtagene autoleucel; HR, hazard ratio; PFS, progression-free survival; SOC, standard care.
aConstant piecewise weighted log-rank test.
bHR and 95% CI from a Cox proportional hazards model with treatment as the sole explanatory variable, including only PFS events that occurred >8 weeks post randomization.
cNominal P value.


CARTITUDE-4: Efficacy - OS, PFS, and MRD-Negativity Rates with CARVYKTI Compared to Standard Care Across Subgroups - Interim Analysis6,7
Characteristic

OS
HRa (95% CI)
PFS
HRb (95% CI)
MRD Negativity
OR (95% CI)
ISS stagec
   I
0.61 (0.37-1.00)
0.28 (0.19-0.41)
6.90 (3.99-11.96)
   II
0.44 (0.78-0.25)
0.31 (0.18-0.51)
7.19 (3.09-16.75)
   III
1.14 (0.40-3.26)
0.41 (0.16-1.09)
12.00 (1.76-81.74)
Soft-tissue plasmacytomas
   Yes
0.62 (0.32-1.21)
0.36 (0.20-0.66)
2.52 (0.90-7.03)
   No
0.53 (0.35-0.81)
0.28 (0.20-0.39)
9.69 (5.85-16.06)
Tumor burdend
   Low
0.56 (0.34-0.94)
0.27 (0.18-0.41)
7.01 (3.94-12.45)
   Intermediate
0.59 (0.31-1.13)
0.34 (0.19-0.60)
5.13 (2.22-11.85)
   High
0.48 (0.23-0.99)
0.21 (0.10-0.44)
24.18 (4.81-121.63)
Cytogenetic risk at study entry
   High riske
12.77 (6.96-23.44)
      Any of 4 markers abnormal
0.54 (0.35-0.85)
0.29 (0.20-0.41)
-
      ≥2 of 4 markers abnormal
0.57 (0.30-1.07)
0.30 (0.17-0.54)
-
      Excl. gain/amp(1q)
0.56 (0.32-0.96)
0.26 (0.16-0.42)
-
   Standard risk
0.62 (0.33-1.19)
0.32 (0.18-0.59)
3.40 (1.65-7.00)
Number of lines of prior therapy
   1
0.56 (0.28-1.11)
0.41 (0.25-0.67)
6.48 (3.03-13.84)
   2 or 3
0.57 (0.38-0.86)
0.26 (0.18-0.37)
7.66 (4.40-13.34)
Refractory to
   PI + immunomodulatory drug
0.51 (0.32-0.82)
0.25 (0.17-0.38)
8.51 (4.31-16.76)
   Anti-CD38 + immunomodulatory drug
0.70 (0.37-1.30)
0.25 (0.14-0.44)
13.23 (3.62-48.32)
   PI + anti-CD38 + immunomodulatory
   drug
0.53 (0.24-1.20)
0.17 (0.08-0.38)
11.85 (2.39-58.82)
   Last line of prior therapy
0.55 (0.39-0.79)
0.30 (0.22-0.40)
7.44 (4.74-11.68)
Prior exposure to
   Daratumumab
0.61 (0.33-1.12)
0.24 (0.14-0.42)
25.00 (5.49-113.77)
   Bortezomib
0.55 (0.38-0.78)
0.30 (0.22-0.40)
7.19 (4.58-11.30)
   Bortezomib and daratumumab
0.53 (0.28-1.00)
0.24 (0.13-0.43)
22.08 (4.81-101.32)
Daratumumab naïve
   Yes
0.56 (0.36-0.86)
0.31 (0.22-0.44)
6.36 (3.88-10.44)
   No
0.61 (0.33-1.12)
0.24 (0.14-0.42)
-
Age
   <65 years
-
-
7.79 (4.35-13.93)
   65-75 years
-
-
5.86 (2.89-11.91)
Abbreviations: CD, cluster of differentiation; CI, confidence interval; HR, hazard ratio; ISS, International Staging System; MRD, minimal residual disease; OR, odds ratio; OS, overall survival; PFS, progression-free survival; PI, proteasome inhibitor. aHRs and 95% CIs from a Cox proportional hazards model with treatment as the sole explanatory variable. HR <1 indicates an advantage for the CARVYKTI arm.
bHRs and 95% CIs from a Cox proportional hazards model with treatment as the sole explanatory variable, including only PFS events that occurred >8 weeks after randomization. cBased on serum β2-microglobulin and albumin.dLow tumor burden defined as meeting all of the following parameters (as applicable): bone marrow % plasma cell <50%, serum M-protein <3 g/dL, serum free light chain <3000 mg/L; high tumor burden defined as meeting any of the following parameters: bone marrow % plasma cell ≥80%, serum M-protein ≥5 g/dL, serum free light chain ≥5000 mg/L; intermediate tumor burden did not fit either criteria of high or low tumor burden.
ePositive for del(17p), t(14;16), t(4;14), and/or gain/amp(1q) by fluorescence in situ hybridization testing.
Protocol-defined high-risk cytogenetics refers to any of 4 markers abnormal.

CARTITUDE-4: Efficacy - Response Rates - Interim Analysis6
CARVYKTI
(n=208)
Standard Care
(n=211)
ORRa, n (%)
176 (84.6)
142 (67.3)
   sCR (%)
69.2
18.5
   CR (%)
7.7
5.7
   VGPR (%)
4.3
22.3
   PR (%)
3.4
20.9
≥CR (%)
76.9
24.2
Median DORb, months (95% CI)
NR (NE-NE)
18.7 (12.9-23.7)
30-month DORb rate, % (95% CI)
67.4 (59.7-74.0)
35.5 (27.6-43.6)
Abbreviations: CI, confidence interval; CR, complete response; DOR, duration of response; IMWG, International Myeloma Working Group; NE, not estimable; NR, not reached; ORR, overall response rate; PR, partial response; sCR, stringent complete response; VGPR, very good partial response.
aAssessed using a validated computerized algorithm; ORR is defined as the proportion of subjects who achieve a PR or better per IMWG criteria. bAnalyzed among responders.

Safety

  • In both the CARVYKTI arm and standard care arm, approximately 97% of patients experienced grade 3/4 TEAEs, with cytopenia being the most frequent TEAE.6
  • No new cases of CNP or MNT were reported for the CARVYKTI arm since the previous report.1,6
  • Infections, cause of death, and SPM were evaluated for both the CARVYKTI and standard care arms and are presented in Table: CARTITUDE-4: Infections, Cause of Death, and SPM - Interim Analysis.

CARTITUDE-4: Infections, Cause of Death, and SPM - Interim Analysis6
CARVYKTI
(n=208)
Standard Care (n=208)
TE infections, %
   All grade
63.5
76.4
   Grade 3/4
28.4
29.8
Deaths due to TE and non-TE infections, n
16
19
   In first year
13
8
   In second year
2
8
Deaths, n
50
82
   Due to progressive disease
21
51
   Due to TEAE
12
8
SPMs, n (%)
27 (13.0)
24 (11.5)
   Hematologica
7 (3.4)
1 (0.5)
      MDS, n
4
0
         Progressed to AML, n
2
-
      AML, n
1
0
      Peripheral T-cell lymphoma, n
2
0
      EBV-associated lymphoma, n
0
1
   Cutaneous/non-invasivea
15 (7.2)
15 (7.2)
   Noncutaneous/invasivea
6 (2.9)
8 (3.8)
Abbreviations: AML, acute myeloid lymphoma; EBV, Epstein-Barr virus; MDS, myelodysplastic syndrome; SPM, second primary malignancy; TE, treatment-emergent; TEAE, treatment-emergent adverse event. aMultiple SPMs could occur in the same patient.

Pharmacokinetics

  • Compared with patients with MRD-positive ≥CR, those with MRD-negative ≥CR had lower levels of inflammatory cytokines before infusion, higher levels of naive T cells, lower levels of effector memory T cells at apheresis, higher peak CAR+ T-cell expansion, and comparable levels of pre-infusion sBCMA.7

CLINICAL DATA - CARTITUDE-4 Subgroup analysEs

PFS in CARTITUDE-4 Subgroups of Patients With High-Risk Disease Features

PFS was analyzed in subgroups of patients with high-risk disease features in both the ITT and as-treated populations in the CARTITUDE-4 study.1,8

Results

Efficacy

ITT Population
  • At a median follow-up of 15.9 months (range, 0.1-27.3), CARVYKTI demonstrated improved PFS vs standard care in all analyzed subgroups in the ITT population, including patients with high-risk cytogenetics, International Staging System stage III disease, soft-tissue plasmacytomas and prior triple-class exposure. PFS in this population is presented in Table: CARTITUDE-4: PFS Subgroup Analysis (ITT Population).8
As-Treated Population

CARTITUDE-4: PFS Subgroup Analysis (ITT Population)8
Characteristic
Median PFS, Months (95% CI)
Hazard Ratioa
(95% CI)
CARVYKTI
(n=208)
Standard care
(n=211)
ISS stageb
   I
NR (19.3-NE)
14.7 (11.2-21.0)
0.30 (0.19-0.48)
   II
NR (18.4-NE)
6.2 (4.1-11.8)
0.21 (0.11-0.42)
   III
17.3 (2.9-NE)
3.4 (2.5-11.5)
0.33 (0.11-0.95)
Soft-tissue plasmacytomas
   Yes
15.8 (3.6-NE)
4.7 (3.1-8.4)
0.39 (0.21-0.75)
   No
NR (22.8-NE)
12.9 (10.5-16.0)
0.22 (0.14-0.34)
Tumor burdenc
   Low
NR (19.3-NE)
14.0 (10.5-20.6)
0.27 (0.17-0.44)
   Intermediate
NR (18.0-NE)
11.8 (4.7-NE)
0.26 (0.12-0.56)
   High
11.7 (6.1-NE)
4.7 (3.1-7.6)
0.27 (0.13-0.56)
Cytogenetic risk
   High riskd
      Any of 4 markers abnormal
NR (18.4-NE)
10.3 (7.6-12.5)
0.25 (0.16-0.38
      ≥2 markers abnormal
18.0 (10.8-NE)
6.7 (4.7-10.3)
0.33 (0.17-0.64)
      del(17p), t(14;16), or t(4;14)
19.3 (18.0-NE)
9.1 (5.1-11.8)
0.26 (0.15-0.45)
   Standard Risk
NR (NE-NE)
20.6 (11.2-NE)
0.40 (0.21-0.77)
Number of lines of prior therapy
   1
NR (NE-NE)
17.4 (11.1-NE)
0.35 (0.19-0.66)
   2 or 3
NR (19.2-NE)
10.2 (6.2-12.2)
0.24 (0.16-0.37)
Refractory to
   PI + immunomodulatory drug
22.8 (18.0-NE)
7.8 (4.7-11.5)
0.24 (0.14-0.38)
   Anti-CD38 + immunomodulatory drug
18.0 (9.3-22.8)
4.3 (3.4-5.7)
0.26 (0.14-0.50)
   Triple-classe
19.3 (2.6-NE)
4.1 (3.1-7.8)
0.15 (0.05-0.39)
   Neither anti-CD38 nor PI
NR (NE-NE)
17.41 (12.0-22.4)
0.20 (0.10-0.39)
   Last line of prior therapy
NR(22.8-NE)
11.8 (9.7-14.0)
0.27 (0.19-0.39)
Prior exposure to
   Daratumumab
19.2 (9.7-NE)
4.5 (3.6-7.5)
0.23 (0.12-0.44)
   Bortezomib
NR (22.8-NE)
11.9 (9.8-14.0)
0.27 (0.19-0.39)
   Triple-classe
19.2 (9.7-NE)
4.7 (3.6-7.5)
0.26 (0.14-0.48)
Bridging therapy/SOC
   PVd
11.7 (2.1-NE)
5.0 (3.4-10.5)
0.31 (0.13-0.72)
   DPd
NR (22.8-NE)
12.5 (10.3-16.0)
0.26 (0.18-0.39)
Abbreviations: CD, cluster of differentiation; CI, confidence interval; DPd, daratumumab, pomalidomide, and dexamethasone; ISS, International Staging System; ITT, intent-to-treat; NE, not estimable; NR, not reached; PFS, progression-free survival; PI, proteasome inhibitor; PVd, pomalidomide, bortezomib, and dexamethasone; SOC, standard care.
a Hazard ratio and 95% CI from a Cox proportional hazards model with treatment as the sole explanatory variable, including only PFS events that occurred >8 weeks after randomization. A hazard ratio <1 indicates an advantage for the CARVYKTI arm.b Based on serum β2-microglobulin and albumin.
c High tumor burden defined as meeting any of the following criteria at baseline: ≥80% bone marrow plasma cells, ≥5 g/dL serum M protein, or ≥5000 mg/L serum free light chain; low tumor burden defined as meeting all the following criteria (as applicable to the patient) at baseline: <50% bone marrow plasma cells, <3 g/dL serum M protein, or <3000 mg/L serum free light chain; intermediate tumor burden did not fit criteria for high or low.
dAny of the 4 following features: del(17p); t(14;16), t(4;14) or gain/amp (1q).
ePI + immunomodulatory drug + anti-CD38 antibody.

CARTITUDE-4: PFS Subgroup Analysis (As-Treated Population)8
Characteristic
12-Month PFS Rate, % (95% CI)
CARVYKTI (n=176)
Cytogenetic riska
   Standard risk
89.6 (78.4-95.2)
   High riskb
88.5 (80.7-93.3)
      ≥2 abnormalities
82.4 (64.9-91.7)
      del(17p), t(14;16), or t(4;14)
86.4 (74.7-93.0)
Soft tissue plasmacytomasc
   Yes
86.7 (68.3-94.8)
   No
90.3 (84.1-94.1)
Refractoriness
   Not triple-refractory  
89.7 (83.7-93.5)
   Triple-class refractoryd
90.0 (65.6-97.4)
Treatment history
   All Patients
84.9 (78.2-89.7)
   Daratumumab exposed
82.8 (65.7-91.9)
   Triple-class exposedd
83.3 (66.5-92.1)
Abbreviations: CD, cluster of differentiation; CI, confidence interval; PFS, progression-free survival; PI, proteasome inhibitor.
aCytogenetics data available in 175 of 176 patients.
bAny of the 4 following features: del(17p), t(14;16), t(4;14), or gain/amp(1q).
cSoft-tissue plasmacytomas included extramedullary plasmacytomas and bone-based plasmacytomas with a measurable soft-tissue component.
dPI + immunomodulatory drug + anti-CD38 antibody.

CARTITUDE-4 Subgroup Analysis in Patients with Functional High-Risk MM

Efficacy and safety outcomes were evaluated in patients who received 1 prior LOT, including the subset of patients with functionally high-risk MM, in the CARTITUDE-4 study.9

Results

Patient Demographics and Disease/Treatment Characteristics

  • A total of 136 patients received 1 prior LOT in the CARTITUDE-4 study.9
    • In the CARVYKTI arm, 68 patients underwent apheresis/bridging therapy; 40 patients had functionally high-risk MM. Of the 68 patients, 60 received CARVYKTI as study treatment; 35 patients had functionally high-risk MM.9
    • A total of 68 patients received standard care; 39 of these patients had functionally high-risk MM.9
    • Functionally high-risk MM defined as progressive disease (PD) ≤18 months after receiving autologous stem cell transplant (ASCT) or the start of initial frontline therapy in patients with no ASCT.9
  • Patient details and a summary of prior therapies for these subgroups are presented in Table: CARTITUDE-4: Baseline Demographics and Disease Characteristics of Patients With 1 Prior LOT and Those With 1 Prior LOT and Functionally High-Risk MM.9

CARTITUDE-4: Baseline Demographics and Disease Characteristics of Patients With 1 Prior LOT and Those With 1 Prior LOT and Functionally High-Risk MM9
Characteristic
1 Prior LOT
1 Prior LOT and Functionally High-Risk MM
CARVYKTI
(n=68)
Standard Care
(n=68)
CARVYKTI
(n=40)
Standard Care
(n=39)
Age, median (range), years
60.5 (27-78)
60.0 (35-78)
60.0 (27-71)
60.0 (40-78)
Male, n (%)
36 (52.9)
42 (61.8)
18 (45.0)
27 (69.2)
ISS stage II/IIIa,n (%)
20 (29.4)
22 (32.4)
12 (30.0)
14 (35.9)
Prior ASCT, n (%)
56 (82.4)
60 (88.2)
33 (82.5)
33 (84.6)
Prior anti-CD38 antibody exposureb, n (%)
2 (2.9)
3 (4.4)
2 (5.0)
1 (2.6)
High-risk cytogeneticsc, n (%)
39 (57.4)
45 (66.2)
22 (55.0)
27 (69.2)
   del17p
14 (20.6)
15 (22.1)
9 (22.5)
9 (23.1)
   t(4;14)
13 (19.1)
10 (14.7)
8 (20.0)
6 (15.4)
   t(14;16)
1 (1.5)
3 (4.4)
0
2 (5.1)
   Gain/amp(1q)
34 (50.0)
38 (55.9)
20 (50.0)
23 (59.0)
   With ≥2 high-risk abnormalities
20 (29.4)
20 (29.4)
13 (32.5)
12 (30.8)
High tumor burdenc,n (%)
9 (13.2)
8 (11.8)
5 (12.5)
4 (10.3)
Soft tissue plasmacytomad,n (%)
12 (17.6)
7 (10.3)
6 (15.0)
4 (10.3)
Abbreviations: ASCT, autologous stem cell transplant; CD, cluster of differentiation; ISS, International Staging System; LOT, line of therapy; MM, multiple myeloma.
aBased on serum β2-microglobulin and albumin.
bPer study design, all patients had also received a proteosome inhibitor and immunomodulatory drug, ie, those with anti-CD38 antibody exposure were triple class exposed.
cHigh- risk cytogenetics was defined as any of the following 4 cytogenetic features abnormal: del17p, t(14;16), t(4;14), or gain/amp(1q).
dHigh tumor burden defined as meeting any of the following criteria at baseline: ≥80% bone marrow plasma cells, ≥5 g/dL serum M protein level, or ≥5000 mg/L serum free light chain.
eSoft tissue plasmacytomas include extramedullary and bone-based plasmacytomas with a measurable soft tissue component.

Efficacy


CARTITUDE-4: Efficacy Outcomes in CARVYKTI vs Standard Care Patients With 1 Prior LOT and Those With 1 Prior LOT and Functionally High-Risk MM9
Responsea
1 Prior LOT
1 Prior LOT and Functionally
High-Risk MM
CARVYKTI
(n=68)
Standard Care
(n=68)
Odds Ratio
(95% CI)
CARVYKTI
(n=40)
Standard Care
(n=39)
Odds Ratio
(95% CI)
ORRb, %
89.7
79.4
-
87.5
79.5
-
   sCR
52.9
23.5
-
45.0
28.2
-
   CR
17.6
11.8
-
22.5
10.3
-
   VGPR
11.8
23.5
-
12.5
15.4
-
   PR
7.4
20.6
-
7.5
25.6
-
≥CR, %
70.6
35.3
4.4
(2.1-9.0)c,d
67.5
38.5
3.3
(1.3-8.4)c,e
MRD-negativity
(10-5)f, %
63.2
19.1
7.3
(3.3-15.9)c,g
65.0
10.3
16.3
(4.8-55.1)c,g
Median DORh,i, months (95% CI)
NR
(NE-NE)
19.81
(14.06-NE)
-
NR
(15.70-NE)
16.36
(8.31-NE)
-
   12-month DOR
   rate, % (95% CI)
81.8
(68.4-89.9)
68.8
(54.0-79.6)
-
79.5
(59.0-90.5)
55.8
(36.1-71.7)
-
Median PFSh
months (95% CI)
NR
(NE-NE)j,k,l
17.41
(11.10-NE) j,k,l
-
NR
(18.00-NE)k,l,m
11.79
(8.44-NE) k,l,m
-
   12-month PFS
   rate, % (95% CI)
77.7
(65.8-85.9)
58.5
(45.5-69.4)
-
77.0
(60.3-87.3)
49.1
(32.4-63.8)
-
Abbreviations: CI, confidence interval; CR, complete response; DOR, duration of response; HR, hazard ratio; IMWG, International Myeloma Working Group; LOT, line of therapy; MM, multiple myeloma; MRD, minimal residual disease; NE, not estimable; NR, not reached; ORR, overall response rate; PD, progressive disease; PFS, progression-free survival; PR, partial response; sCR, stringent complete response; VGPR, very good partial response.aTreatment response was assessed by a validated computerized algorithm, based on IMWG consensus criteria. bORR was defined as the proportion of patients who achieve a PR or better.
cMantel-Haenszel estimate of the common odds ratio for unstratified tables is used.
dP<0.0001; P value was calculated using the Cochran-Mantel-Haenszel Chi-squared test.
eP=0.0102; P value was calculated using the Cochran-Mantel-Haenszel Chi-squared test.
fMRD-negativity (10-5 threshold) was based on next-generation sequencing and post randomization assessment. Overall rate reflects patients with MRD-negativity by bone marrow aspirate at any time after the randomization date and before PD or subsequent antimyeloma treatment.
gP<0.0001; P value was calculated using the Fisher’s exact test.
hAssessed using a validated computerized algorithm.
iDetermined among responders.
jHR (95% CI): 0.35 (0.19-0.66); P=0.0007.
kHR and 95% CI from a Cox proportional hazards model with treatment as the sole explanatory variable, including only PFS events that occurred >8 weeks after randomization.
lP value based on the constant piecewise weighted log-rank test, where the weight equals 0 in the log-rank statistic for the first 8 weeks after randomization and 1 week afterward.
mHR (95% CI): 0.27 (0.12-0.60); P=0.0006.

CARTITUDE-4: Efficacy Outcomes in CARVYKTI-Treated Patients With 1 Prior LOT and Those With 1 Prior LOT and Functionally High-Risk MM9
Responsea
1 Prior LOT
(n=60)
1 Prior LOT and Functionally High-Risk MM
(n=35)
ORRb, %
100
100
   sCR
60.0
51.4
   CR
20.0
25.7
   VGPR
13.3
14.3
   PR
6.7
8.6
≥CR, %
80.0
77.1
MRD-negativity (10-5)c, n (%)
43 (71.6)
26 (74.3)
Median PFS, months (95% CI)
NR (NE-NE)
NR (18.0-NE)
   12-month PFS, % (95% CI)
88.1 (76.6-94.1)
88.0 (70.9-95.3)
Abbreviations: CI, confidence interval; CR, complete response; IMWG, International Myeloma Working Group; LOT, line of therapy; MM, multiple myeloma; MRD, minimal residual disease; NE, not estimable; NR, not reached; ORR, overall response rate; PD, progressive disease; PFS, progression-free survival; PR, partial response; sCR, stringent complete response; VGPR, very good partial response.
aTreatment response was assessed by a validated computerized algorithm based on IMWG consensus criteria.
bORR was defined as the proportion of patients who achieve a PR or better.
cMRD-negativity (10-5 threshold) was based on next generation sequencing and post randomization assessment. Overall rate reflects patients with MRD-negativity by bone marrow aspirate at any time after the randomization date and before PD or subsequent antimyeloma treatment.

Safety


CARTITUDE-4: Frequency of AEs in Patients With 1 Prior LOT and Those With 1 Prior LOT and Functionally High-Risk MM9
1 Prior LOT
1 Prior LOT and Functionally High-Risk MM
CARVYKTI
(n=68)
Standard Care
(n=68)
CARVYKTI
(n=40)
Standard Care
(n=39)
Grade ≥3 TEAEs, n (%)
65 (95.6)
65 (95.6)
40 (100.0)
38 (97.4)
Serious TEAEs, n (%)
26 (38.2)
24 (35.3)
16 (40.0)
13 (33.3)
Abbreviations: AE, adverse event; LOT, line of therapy; MM, multiple myeloma; TEAE, treatment-emergent adverse event.

CARTITUDE-4: AEs of Special Interest in CARVYKTI Patients With 1 Prior LOT and Those With 1 Prior LOT and Functionally High-Risk MM9
AEsa, n (%)
1 Prior LOT

1 Prior LOT and Functionally High-Risk MM

CARVYKTI
(n=68)
CARVYKTI
(n=68)
CARVYKTI
(n=40)
CARVYKTI
(n=40)
All
Grade 3 or 4
All
Grade 3 or 4
   CRSb
44 (64.7)
1 (1.5)
25 (62.5)
0
   ICANSc
2 (2.9)
0
2 (5.0)
0
   Cranial nerve palsy
6 (8.8)
2 (2.9)
3 (7.5)
0
   Movement and neurocognitive TEAEs
1 (1.5)
0
0
0
   Peripheral neuropathy
2 (2.9)
0
2 (5.0)
0
Abbreviations: AE, adverse event; ASTCT, American Society for Transplantation and Cellular Therapy; CRS, cytokine release syndrome; ICANS, immune effector cell-associated neurotoxicity syndrome; LOT, line of therapy; MM, multiple myeloma; NCI-CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events, TEAE, treatment-emergent adverse event.
aAEs of special interest were evaluated in all patients receiving CARVYKTI as second-line treatment (n=68) and in those with functionally high-risk MM status (n=40). AEs were graded per NCI-CTCAE criteria version 5.0.
bCRS was assessed per ASTCT criteria.
cICANS was assessed per ASTCT criteria.


Pharmacokinetics

CARTITUDE-4:  CAR+ CD4:CD8 T-Cell Ratios in Patients With 1 Prior LOT With and Without Functionally High-Risk MM Status9

A screenshot of a graph Description automatically generated

Abbreviations: CAR, chimeric antigen receptor; CD, cluster differentiation; LOT, line of therapy; MM, multiple myeloma.
aNumbers (n)’s are based on randomly assigned patients in the CARVYKTI arm with available data on CAR+ T-cell characterization and CAR+ T-cell peak expansion.

CARTITUDE-4: CAR-T Peak Expansion and Baseline sBCMA in Patients With 1 Prior LOT With and Without Functionally High-Risk MM Status9

A screenshot of a computer screen Description automatically generated

Abbreviations: CAR, chimeric antigen receptor; Cmax, maximum observed concentration of CAR+ T cells in blood; LOT, line of therapy; MM, multiple myeloma; sBCMA, soluble B-cell maturation antigen.
aNumbers (n) are based on randomly assigned patients in the CARVYKTI arm with available data on CAR+ T-cell characterization and CAR+ T-cell peak expansion.

CARTITUDE-4 Subgroup Analysis by Cytogenetic Risk

Efficacy of CARVYKTI compared to standard care in patients was evaluated in patients with high-risk cytogenetic abnormalities in the CARTITUDE-4 study.10

Results

Patient Demographics and Disease/Treatment Characteristics

  • Baseline characteristics of patients with high-risk cytogenetics in the CARVYKTI and standard care arms are presented in Table: CARTITUDE-4: Baseline Characteristics of Patients With High-Risk Cytogenetics.10
  • Patients with high-risk cytogenetics had ≥1 of the following cytogenetic abnormalities at baseline determined by fluorescence in situ hybridization:
    t(4;14), del(17p), t(14;16), or gain/amp(1q).10

CARTITUDE-4: Baseline Characteristics of Patients With High-Risk Cytogenetics10
Characteristic
CARVYKTI
(n=123)
Standard Care
(n=132)
Age, median (range), years
62 (40-78)
62 (35-80)
Male, n (%)
65 (52.8)
71 (53.8)
Cytogenetic high-risk abnormality, n (%)
   gain/amp(1q)
89 (72.4)
107 (81.1)
   del(17p)
49 (39.8)
43 (32.6)
   t(4;14)
30 (24.4)
30 (22.7)
   t(14;16)
3 (2.4)
7 (5.3)
   ≥2 high-risk abnormalities
43 (35.0)
49 (37.1)
   del(17p), t(14;16), or t(4;14)
73 (59.3)
69 (52.3)
ISS stage, n (%)
   I
77 (62.6)
79 (59.8)
   II
38 (30.9)
46 (34.8)
   III
8 (6.5)
7 (5.3)
Soft tissue plasmacytomas, n (%)
27 (22.0)
20 (15.2)
Median years since diagnosis, (range)
3.2 (0.5-12.1)
3.4 (0.5-13.2)
Prior LOT, median (range)
   1
39 (31.7)
45 (34.1)
   2-3
84 (68.3)
87 (65.9)
Previous ASCT, n (%)
104 (84.6)
120 (90.9)
Triple-class exposeda, n (%)
33 (26.8)
34 (25.8)
Refractory status, n (%)
   Daratumumab
29 (23.6)
27 (20.5)
   Triple-classa
17 (13.8)
20 (15.2)
   To last line of therapy
121 (98.4)
130 (98.5)
Bridging therapy, n (%)
   DPd
106 (86.2)
116 (87.9)
   PVd
17 (13.8)
16 (12.1)
Abbreviations: ASCT, autologous stem cell transplant; CD, cluster of differentiation; DPd, daratumumab, pomalidomide, dexamethasone; ISS, International Staging System; LOT, line of treatment; PI, proteasome inhibitor; PVd, daratumumab, bortezomib, dexamethasone.
aIncludes ≥1 PI, ≥1 immunomodulatory drug, and 1 anti-CD38 monoclonal antibody.

Efficacy


CARTITUDE-4: Efficacy Outcomes by Cytogenetic Risk10
Response
CARVYKTI
Standard Care
Standard Risk (n=69)
High-Risk Cytogenetics (n=123)
Standard Risk (n=70)
High-Risk Cytogenetics (n=132)
ORR, n (%)
59 (85.5)
105 (85.4)
50 (71.4)
87 (65.9)
   ≥CR
51 (73.9)
90 (73.2)
18 (25.7)
26 (19.7)
MRD-negativity (10-5), n (%)
34 (49.3)
86 (69.9)
13 (18.6)
19 (14.4)
Median PFS, months (95% CI)
NE (NE-NE)
NE (18.4-NE)
20.6 (11.2-NE)
10.3 (7.6-12.5)
Abbreviations: CI, confidence interval; CR, complete response; MRD, minimal residual disease; NE, not estimable; ORR, overall response rate; PFS, progression-free survival.

CARTITUDE-4: Treatment Responses by Cytogenetic Risk Abnormality10
Response
CARVYKTI
Standard Care
t(4;14)
del(17p)
Gain/Amp (1q)
≥2 High-Risk Abnormalities
t(4;14)
del(17p)
Gain/Amp (1q)
≥2 High-Risk Abnormalities
ORR, %
80
80
87
79
67
63
65
63
   ≥CR
77
63
72
63
17
9
22
14
Bone marrow MRD-negativity,
(10-5), %
67
65
71
65
13
9
15
10
Abbreviations: CR, complete response; MRD, minimal residual disease; ORR, overall response rate.

CARTITUDE-4: PFS by High-Risk Cytogenetic Abnormalities10
Cytogenetic Abnormality
CARVYKTI
(Median [95% CI], months)
Standard Care
(Median [95% CI], months)
Hazard Ratio (95% CI)
CARVYKTI High Risk vs Standard Care High Risk
NE (18.4-NE)
10.3 (7.6-12.5)
0.37 (0.25-0.54)
CARVYKTI t(4;14) vs Standard Care t(4;14)
NE (12.9-NE)
6.7 (3.8-13.8)
0.37 (0.17-0.81)
CARVYKTI del(17p) vs Standard Care del(17p)
19.3 (12.9-NE)
8.7 (5.1-11.8)
0.48 (0.27-0.86)
Abbreviations: CI, confidence interval; NE, not estimable; PFS, progression-free survival.

Patient-reported outcomes

PROs and time to next antimyeloma therapy were evaluated at a median follow-up of 33.6 months (range, 0.1-45.0) in both the CARVYKTI and standard care arms.11

Methods

  • PROs were assessed through the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 item (EORTC QLQ-C30) and MySIm-Q. Assessments were conducted at baseline (apheresis for the CARVYKTI arm and cycle 1 day 1 for the standard care arm). Post-baseline assessments were conducted on day 28 post CARVYKTI infusion and at cycle 4 (DPd) or cycle 5 (PVd) in the standard care arm. Additional assessments were conducted at months 3, 6, 9, 12, 18, 24, 30 or until disease progression.11
  • Time to worsening of symptoms and impact were defined as time from randomization to an increase in score of ≥0.5 standard deviation from baseline without superior subsequent improvement observed. If patients had not worsened or started subsequent therapy, they were censored at last PRO. If patients did not have baseline or ≥1 post-baseline PRO assessment, they were also censored at randomization.11
  • Time to next antimyeloma therapy was defined as time from randomization to the start of subsequent antimyeloma therapy or death due to PD (whichever came first).11
  • Treatment-free survival was defined as the duration of time from the date of last study treatment to subsequent therapy or death due to PD (whichever came first).11

Results

PRO Compliance

  • PRO compliance rates are presented in Figure: CARTITUDE-4: PRO compliance rates.11
    • Primary reasons for noncompliance included mistakes, forgetfulness, site errors/oversights, unknown causes, unavailability of site staff, administrative failure, use of paper, tablet issues, and technical failure.11

CARTITUDE-4: PRO Compliance Ratesa,11

A graph of numbers and a number of people Description automatically generated with medium confidence

Abbreviations: cilta-cel, ciltacabtagene autoleucel; EORTC QLQ-C30, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 item; M, month; MySIm-Q, Multiple Myeloma Symptom and Impact Questionnaire; PRO, patient-reported outcome; SOC, standard care.
aCompliance was defined as the number of forms received as a percentage of the number of forms expected.

MySIm-Q Total Symptom and Impact Scales

  • From the MySIm-Q time to sustained worsening analysis, 86% of patients in the CARVYKTI arm and 77% of patients in the standard care arm were censored.11
    • The primary reasons for censoring were PD/receipt of subsequent antimyeloma therapy (CARVYKTI, 32%; standard care, 64%) and study cut-off (CARVYKTI, 57%; standard care, 22%).11
  • The median time to symptom worsening was NR in the CARVYKTI arm and 34.3 months in the standard care arm.11
    • The event-free rate at 30 months was 77% in the CARVYKTI arm and 63% in the standard care arm.11
  • The median time to impact worsening was 39.2 months (95% CI, 38.7-NE) in the CARVYKTI arm and 35.9 months (95% CI, 32.2-NE) in the standard care arm (HR, 0.42; 95% CI, 0.26-0.70; P=0.0007).11
    • The event-free rate at 30 months was 83% in the CARVYKTI arm and 69% in the standard care arm.11
  • The least squares mean change from baseline in the MySIm-Q total symptom and impact scores at month 30 are presented in Figure: CARTITUDE-4: LS Mean Change From Baseline in the MySIm-Q Total Symptom and Impact Scores at Month 30.11

CARTITUDE-4: LS Mean Change From Baseline in the MySIm-Q Total Symptom and Impact Scores at Month 3011

A diagram of a graph Description automatically generated with medium confidence

Abbreviations: BL, baseline; CI, confidence interval; cilta-cel, ciltacabtagene autoleucel; LS, least squares; MySIm-Q, Multiple Myeloma Symptom and Impact Questionnaire; SOC, standard care.

EORTC QLQ-C30 Global Health Status/Quality of Life

CARTITUDE-4: Clinically Meaningful Improvement and LS Mean Change from Baseline on EORTC QLQ-C30 Scales at Month 3011

Abbreviations: BL, baseline; CI, confidence interval; cilta-cel, ciltacabtagene autoleucel; EORTC QLQ-C30, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 item; LS, least squares; SOC, standard care.
aA literature-based minimum importance difference of 10 points was used.

Time to Next Antimyeloma Therapy and Treatment-free Survival

  • The median time to the next antimyeloma therapy was NR (95% CI, 38.4 months-NE) for CARVYKTI and 13.4 months (95% CI, 12.0-17.1) for standard care (HR [95% CI], 0.34 [0.26-0.46]; P<0.0001).11
  • The median treatment-free survival was NR (95% CI, 36.6 months-NE) for CARVYKTI and 1.0 month (95% CI, 0.8-1.2) for standard care.11

Literature Search

A literature search of MEDLINE®, Embase®, BIOSIS Previews®, and Derwent Drug File databases (and/or other resources, including internal/external databases) was conducted on 16 December 2024.

References

Show
1 San-Miguel J, Dhakal B, Yong K, et al. Cilta-cel or standard care in lenalidomide-refractory multiple myeloma. N Engl J Med. 2023;389(4):335-347.  
2 Sidiqi MH, Corradini P, Purtill D, et al. Efficacy and safety in patients with lenalidomide-refractory multiple myeloma and 1-3 prior lines who received a single infusion of ciltacabtagene autoleucel as study treatment in the phase 3 CARTITUDE-4 trial. Poster presented at: 65th American Society of Hematology (ASH) Annual Meeting & Exposition; December 9-12, 2023; San Diego, CA.  
3 Dhakal B, Yong K, Harrison S, et al. Phase 3 results from CARTITUDE-4: cilta-cel versus standard of care (PVd or DPd) in lenalidomide-refractory multiple myeloma. Oral Presentation presented at: American Society of Clinical Oncology (ASCO) Annual Meeting; June 2-6, 2023; Chicago, IL/Virtual.  
4 San-Miguel J, Dhakal B, Yong K, et al. Supplement to: Cilta-cel or standard care in lenalidomide-refractory multiple myeloma. N Engl J Med. 2023;389(4):335-347.  
5 van de Donk NWCJ, Sidana S, Schecter JM, et al. Clinical experience with cranial nerve impairment in the CARTITUDE-1, CARTITUDE-2 cohorts A, B, and C, and CARTITUDE-4 studies of ciltacabtagene autoleucel. Poster presented at: 65th American Society of Hematology (ASH) Annual Meeting and Exposition; December 9-12, 2023; San Diego, CA.  
6 Mateos MV, San-Miguel J, Dhakal B, et al. Overall survival with ciltacabtagene autoleucel versus standard of care in lenalidomide-refractory multiple myeloma: phase 3 CARTITUDE-4 study update. Oral Presentation presented at: 21st International Myeloma Society (IMS) Annual Meeting; September 25-28, 2024; Rio de Janeiro, Brazil.  
7 Popat R, Oriol A, Cavo M, et al. Ciltacabtagene autoleucel vs standard of care in patients with lenalidomide-refractory multiple myeloma after 1-3 lines of therapy: minimal residual disease negativity in the phase 3 CARTITUDE-4 trial. Oral presentation presented at: 66th American Society of Hematology (ASH) Annual Meeting; December 7-10, 2024; San Diego, CA.  
8 Manier S, San-Miguel J, Dhakal B, et al. Additional analysis of CARTITUDE-4: cilta-cel vs standard of care (PVd or DPd) in lenalidomide-refractory patients with multiple myeloma and 1-3 prior lines of therapy. Oral Presentation presented at: International Myeloma Society Annual Meeting; September 27-30, 2023; Athens, Greece.  
9 Costa LJ, Weisel K, van de Donk NWCJ, et al. Ciltacabtagene autoleucel vs standard of care in patients with functional high-risk multiple myeloma: CARTITUDE-4 subgroup analysis. Oral Presentation presented at: The American Society of Clinical Oncology (ASCO) Annual Meeting; May 31-June 4, 2024; Chicago, IL.  
10 Mina R, Dhakal B, San-Miguel3 J, et al. Ciltacabtagene autoleucel vs standard of care in lenalidomide-refractory multiple myeloma: phase 3 CARTITUDE-4 subgroup analysis by cytogenetic risk. Poster presented at: The European Hematology Association (EHA) Meeting; June 13-16, 2024; Madrid, Spain.  
11 Bar N, Mina R, Mylin AK, et al. Long-term benefits in patient-reported outcomes and time to next antimyeloma therapy of ciltacabtagene autoleucel versus standard of care for patients with lenalidomide-refractory multiple myeloma: results from the phase 3 CARTITUDE-4 clinical trial. Poster presented at: American Society of Hematology (ASH) Annual Meeting; December7-10, 2024; San Diego, CA.  
12 Anguille S, Leleu X, Gatt M, et al. Effectiveness of bridging therapy corresponds to improved outcomes after receiving CAR-T therapy in the phase 3 CARTITUDE-4 study of patients with relapsed, lenalidomide-refractory multiple myeloma. Poster presented at: 21st International Myeloma Society (IMS) Annual Meeting; September 25-28, 2024; Rio de Janeiro, Brazil.  
13 van de Donk NWCJ, Martinez-Lopez J, Dhakal B, et al. Infections and immune reconstitution in the phase 3 CARTITUDE-4 trial of ciltacabtagene autoleucel vs standard care in patients with lenalidomide-refractory multiple myeloma and 1-3 prior lines. Poster presented at: International Myeloma Society (IMS) Annual Meeting; September 25-28, 2024; Rio de Janeiro, Brazil.  
14 Janssen Research and Development, LLC. A study comparing JNJ-68284528, a CAR-T therapy directed against b-cell maturation antigen (BCMA), versus pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd) in participants with relapsed and lenalidomide-refractory multiple myeloma (CARTITUDE-4). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2024 December 16]. Available from: https://clinicaltrials.gov/ct2/show/NCT04181827 NLM Identifier: NCT04181827.  
15 de Larrea CF, Harrison SJ, Martínez-López J, et al. Pharmacokinetic and correlative analysis of ciltacabtagene autoleucel in patients With lenalidomide-refractory multiple myeloma in the CARTITUDE-4 trial. Oral Presentation presented at: 20th International Myeloma Society (IMS) Annual Meeting and Exposition; September 27-30, 2023; Athens, Greece.