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DARZALEX® (daratumumab)

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Use of DARZALEX + DARZALEX FASPRO in Pediatric Patients

Last Updated: 02/06/2025

Summary

  • DARZALEX for intravenous (IV) use or DARZALEX FASPRO for subcutaneous (SC) use are not approved by the regulatory agencies for use in pediatric patients. Janssen does not recommend the use of DARZALEX/DARZALEX FASPRO in a manner that is inconsistent with the approved labeling.
  • The safety and efficacy of DARZALEX/DARZALEX FASPRO have not been established in pediatric patients.1,2
  • DELPHINUS is a phase 2 study that evaluated the safety and efficacy of DARZALEX in patients between the ages of ≥1 and ≤30 years with relapsed/refractory (R/R) precursor B-cell or T-cell acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL).3
    • Hogan et al (2022)4 presented (at the 58th American Society of Clinical Oncology [ASCO] Annual Meeting) the initial results of this study that evaluated the efficacy, safety, and pharmacokinetics (PK) of DARZALEX in pediatric (1 to 17 years old) or young adult (18-30 years old) patients with R/R T-cell ALL or LL. At the end of cycle 1, complete response (CR) was achieved in 10 of 24 (41.7%; 90% confidence interval [CI], 24.6-60.3) pediatric patients with T-cell ALL. The most common grade 3/4 treatment-emergent adverse event (TEAE) in pediatric T-cell ALL patients was anemia (66.7%). The most common grade 3/4 infusion-related reaction (IRR) in pediatric patients with T-cell ALL was leukopenia and abdominal pain (4.2% each). The most common grade 3/4 IRR in patients with T-cell LL was thrombocytopenia and bronchospasm (10% each).
    • Bhatla et al (2024)5,6 reported updated results of the phase 2 DELPHINUS study. None of the pediatric patients in the B-cell cohort achieved CR within 2 treatment cycles. However, 1 patient achieved CR with incomplete hematologic recovery (CRi), 3 patients had refractory ALL, and 3 patients experienced progressive disease (PD) as their best response. At the end of cycle 2, the CR rate and overall response rate (ORR) for pediatric patients with T-cell ALL were 50% and 83.3%, respectively. Minimal residual disease (MRD)-negativity at any time during treatment was achieved in 11 (45.8%) pediatric patients with T-cell ALL. Among pediatric patients with T-cell ALL, the median event-free survival (EFS) was 8.9 months and the median relapse-free survival (RFS) for those who achieved CR was 19.4 months. The median overall survival (OS) was 10.9 months (90% CI, 6.7-not estimable [NE]) for pediatric patients with T-cell ALL. No new safety concerns were identified with DARZALEX. Any-grade and grade 3/4 TEAEs occurred in all patients (100%). The most common grade 3/4 TEAEs across the cohorts were hematologic events. Grade 3/4 infections occurred in 1 pediatric patient with B-cell ALL (grade 4 sepsis). IRRs after the first DARZALEX infusion were reported in 4 (57.1%) pediatric patients with B-cell ALL and 16 (66.7%) pediatric patients with T-cell ALL.
  • For information on ongoing clinical trials investigating the use of DARZALEX/DARZALEX FASPRO in pediatric patients, please visit www.clinicaltrials.gov.

PRODUCT LABELING

CLINICAL DATA

  • DELPHINUS (ALL2005; clinicaltrials.gov identifier: NCT03384654) is an open-label, multicenter, phase 2 study evaluating the safety and efficacy of DARZALEX in patients with R/R precursor B-cell or T-cell ALL or LL.3,4 Hogan et al (2022)4 presented the initial results of the phase 2 DELPHINUS study evaluating the efficacy, safety, and PK of DARZALEX in pediatric (1 to 17 years old) or young adult (18-30 years old) patients with R/R T-cell ALL or LL.

Study Design/Methods

  • The study enrolled 47 patients and consists of 2 cohorts. The study design has been presented in the Figure: Study Design.

Study Design3,4

Graphical user interface, text Description automatically generated

Abbreviations: 6-MP, 6-mercaptopurine; allo-HSCT, allogeneic hematopoietic stem cell transplant; BID, twice daily; Cmax, maximum plasma concentration; Cmin, minimum plasma concentration; CP, cyclophosphamide; CR, complete response; CrCl, creatinine clearance; CSF, cerebrospinal fluid; Dara, daratumumab; DXR, doxorubicin; EFS, event-free survival; GFR, glomerular filtration rate; GVHD, graft vs host disease; HSCT, hematopoietic stem cell transplant; IM, intramuscular; IV, intravenous; MRD, minimal residual disease; MTX, methotrexate; ORR, overall response rate; OS, overall survival; Ph+, Philadelphia chromosome positive; PO, orally; PRED, prednisone; PS, performance status; Q2W, twice a week; QD, once daily; QW, once weekly; RFS, relapse-free survival; SC, subcutaneously; ULN, upper limit of normal range; VCR, vincristine.
aB-cell cohort for stage 1: patients aged 1 to <18 years with acute lymphoblastic leukemia in ≥2nd relapse or refractory to 2 prior induction treatments with ≥5% blasts in bone marrow; stage 2: patients aged 1-30 years with acute lymphoblastic leukemia in ≥2nd relapse or refractory to 2 prior induction treatments with ≥5% blasts in bone marrow, acute lymphoblastic lymphoma in ≥2nd relapse or refractory to 2 prior induction regimens with measurable disease.
bT-cell cohort for stage 1: patients aged 1 to <18 years with acute lymphoblastic leukemia in 1st relapse or refractory to 1 prior induction/consolidation treatment with ≥5% blasts in the bone marrow; stage 2: patients aged 1-30 years with acute lymphoblastic leukemia in 1st relapse or refractory to 1 prior induction/consolidation treatment with ≥5% blasts in bone marrow, acute lymphoblastic lymphoma in 1st relapse or refractory to 1 prior induction/consolidation treatment with measurable disease, aged 1-30 years.
cPatients received age/risk-adjusted intrathecal therapy, and those who achieved CR after cycles 1 or 2 could proceed to allo-HSCT off-study.
dFor patients who achieved a CR and required a short interval of treatment prior to transplant, Dara 16 mg/kg IV could be given QW (total of 4 doses) after completion of cycle 1 or Q2W (total of 2 doses) after completion of cycles 2-6 or once after completion of cycles ≥7. There was a 2-week interval from the last dose of Dara and the start of conditioning therapy for the transplant. Other standard maintenance chemotherapy could also be given after the discontinuation of study treatment and prior to transplant.
eMaximum 2 mg.
fCycle 2 was optional to allow further treatment for those who did not achieve CR or to consolidate the response prior to HSCT.
gDuration from the date of first treatment to the first documented treatment failure or date of relapse from CR or death.

Hogan et al (2022)4 presented the initial results of the phase 2 DELPHINUS study evaluating the efficacy, safety, and PK of DARZALEX in pediatric (1 to 17 years old) or young adult (18-30 years old) patients with R/R T-cell ALL or LL.

Study Design/Methods

  • Primary endpoint: CR in pediatric T-cell ALL patients at the end of cycle 1 (null hypothesis [H0], CR rate ≤30%; alternative hypothesis [Ha]: CR rate ≥60%)
  • Secondary endpoints: ORR, percentage of MRD-negative patients, patients receiving allogeneic hematopoietic stem cell transplant (allo-HSCT), maximum plasma concentration (Cmax) and minimum plasma concentration (Cmin) of daratumumab, anti-daratumumab antibodies, concentration of daratumumab in cerebrospinal fluid (CSF), EFS, OS, safety, tolerability, and PK of daratumumab

Results

Patient Characteristics

Baseline Patient and Disease Characteristics4
Characteristic
T-Cell ALL
T-Cell LL
(n=10)
Pediatric Patients
(n=24)
Young Adult Patients
(n=5)
Median age (range), years
10 (2-17)
23 (18-25)
14.5 (5-22)
Sex, n (%)
   Male
14 (58.3)
5 (100)
9 (90)
   Female
10 (41.7)
0 (0)
1 (10)
Median time from initial diagnosis to first dose (range), years
2.5 (0.5-6.1)
0.6 (0.1-5.6)
0.8 (0.5-6)
Cycle of treatment received, n
   Cycle 1
22
5
10
   Cycle 2
18
3
6
   DARZALEX continuation
6
1
0 (0)
CNS involvement at study entry, n (%)
4 (16.7)
2 (40)
2 (20)
Abbreviation: ALL, acute lymphoblastic leukemia; CNS, central nervous system; LL, lymphoblastic lymphoma.
Efficacy
  • The median (range) follow-up duration for the pediatric/young adult T-cell ALL, young adult T-cell ALL, and T-cell LL groups was 31.3 (0.8-40.1), 25.4 (2.6-25.4), and 16.4 (1.6-19) months, respectively.
  • At the end of cycle 1, CR was achieved in 10 of 24 (41.7%; 90% CI, 24.6-60.3) pediatric patients with T-cell ALL.
  • Efficacy outcomes are summarized in Table: Efficacy Outcomes.

Efficacy Outcomes4
Parameter
T-Cell ALL
T-Cell LL
(n=10)
Pediatric Patients
(n=24)
Young Adult Patients
(n=5)
ORRa,b, n (%)
20 (83.3)
3 (60)
5 (50)
   90% CI
65.8-94.1
18.9-92.4
15-69.7
CRa,c, n (%)
13 (54.2)
3 (60)
4 (40)
CRia, n (%)
7 (29.2)
-
-
PRa, n (%)
-
-
1 (10)
MRD-negativitya, n (%)
10 (41.7)
1 (20)
5 (50)
Median EFSd, months (90% CI)
8.3 (5.3-20.5)
8 (2.6-NE)
2.9 (1.3-4.9)
Median OSe, months (90% CI)
9.5 (7-NE)
13.6 (4.5-NE)
4.2 (1.7-5.6)
Abbreviations: ALL, acute lymphoblastic leukemia; CI, confidence interval; CR, complete response; CRi, complete response with incomplete hematologic recovery; EFS, event-free survival; LL, lymphoblastic lymphoma; MRD, minimal residual disease; NE, not estimable; ORR, overall response rate; OS, overall survival; PR, partial response.aAt any time during treatment.bORR data after Cycle 2 will be available at end of study
cCriteria for CR: bone marrow blasts, <5%; absolute neutrophil count, >1×109/L; platelet count, >100×109/L; No evidence of circulating blasts or extramedullary disease
dEFS was defined as the time from the date of first treatment to the first documented treatment failure or date of relapse from CR or death due to any cause, whichever occurred first.
eOS was measured from the date of first treatment to the date of death due to any cause.
Safety

Grade 3/4 TEAEs (≥20%) in Pediatric Patients with T-cell ALL4
Event, n (%)
T-Cell ALL
Pediatric Patients
(n=24)
Hematologic
   Anemia
16 (66.7)
   Thrombocytopenia
15 (62.5)
   Neutropenia
12 (50)
   Febrile neutropenia
11 (45.8)
   Leukopenia
9 (37.5)
Nonhematologic
   Increased alanine aminotransferase
6 (25)
   Hypokalemia
6 (25)
Abbreviation: ALL, acute lymphoblastic leukemia; TEAE, treatment-emergent adverse event.
  • Among pediatric patients with T-cell ALL, none discontinued DARZALEX due to adverse events (AEs), and 1 (4.2%) death reported due to TEAEs (brain edema and hepatic failure) related to the study treatment but unrelated to DARZALEX.
  • ≥ IRRs of any grade were reported in 16 (66.7%) pediatric patients with T-cell ALL, 4 (80%) young adult patients with T-cell ALL, and 8 (80%) patients with T-cell LL. See Table: Infusion-Related Reactions.

Infusion-Related Reactions4
IRR, n (%)
T-Cell ALL
T-Cell LL
(n=10)
Pediatric Patients
(n=24)
Young Adult Patients
(n=5)
Any grade occurring in >10% of patients
   Abdominal pain
6 (25)
0 (0)
1 (10)
   Pyrexia
4 (16.7)
0 (0)
1 (10)
   Vomiting
3 (12.5)
0 (0)
1 (10)
   Nausea
3 (12.5)
0 (0)
0 (0)
   Cough
3 (12.5)
0 (0)
4 (40)
   Urticaria
3 (12.5)
0 (0)
0 (0)
   IRR
2 (8.3)
1 (20)
0 (0)
   Rash
1 (4.2)
1 (20)
0 (0)
   Dyspnea
1 (4.2)
0 (0)
3 (30)
   Pruritus
0 (0)
1 (20)
1 (10)
   Rhinitis
0 (0)
1 (20)
0 (0)
   Increased gamma-glutamyltransferase
0 (0)
1 (20)
0 (0)
   Musculoskeletal chest pain
0 (0)
1 (2)
0 (0)
Grade 3/4 occurring in any patients
   Leukopenia
1 (4.2)
0 (0)
0 (0)
   Abdominal pain
1 (4.2)
0 (0)
0 (0)
   Thrombocytopenia
0 (0)
0 (0)
1 (10)
   Bronchospasm
0 (0)
0 (0)
1 (10)
Abbreviation: ALL, acute lymphoblastic leukemia; IRR, infusion-related reaction; LL, lymphoblastic lymphoma.
Pharmacokinetics
  • The mean serum trough concentration (Ctrough) for daratumumab was 361 (standard deviation [SD], 106) μg/mL at cycle 2 day 22 in pediatric patients with T-cell ALL.
  • The mean CSF Ctrough of daratumumab was 1.07 μg/mL at cycle 2 day 15.

Bhatla et al (2024)5,6 reported updated results of the phase 2 DELPHINUS study that evaluated the efficacy and safety of DARZALEX in pediatric (1-17 years old) patients with B-cell or T-cell ALL (stage 1) and young adult (18-30 years old) patients with T-cell ALL or LL (stage 2).

Study Design/Methods

  • Primary endpoint: CR rate in patients with B-cell ALL within 2 cycles of therapy or CR rate in patients with T-cell ALL at the end of cycle 1 (defined as <5% bone marrow blasts, absence of circulating blasts or extramedullary disease, and full recovery of the absolute neutrophil count [>1×109/L] and platelet count [>100×109/L]).5
  • Secondary endpoints: ORR (CR + CRi at any time before the start of subsequent therapy or hematopoietic stem cell transplant [HSCT] for patients with ALL and CR + partial response for patients with LL), percentage of MRD-negative patients, EFS, RFS, OS, safety, and PK of daratumumab.5

Results

Patient Characteristics

Demographic and Baseline Characteristics For B-Cell and T-Cell Cohorts5
Characteristic
B-Cell ALL
T-Cell ALL
T-Cell LL
(n=10)
Pediatric Patients
(n=7)
Pediatric Patients
(n=24)
Young Adult Patients
(n=5)
Median age (range), years
5 (4-17)
10 (2-17)
23 (18-25)
14.5 (5-22)
Sex, n (%)
   Male
3 (42.9)
14 (58.3)
5 (100)
9 (90)
   Female
4 (57.1)
10 (41.7)
0 (0)
1 (10)
Race, n (%)
   White
5 (71.4)
18 (75)
2 (40)
8 (80)
   Asian
0 (0)
1 (4.2)
1 (20)
0 (0)
   Black/African American
0 (0)
0 (0)
1 (20)
0 (0)
   American Indian/Alaska Native
0 (0)
0 (0)
1 (20)
0 (0)
   Not reported
2 (28.6)
5 (20.8)
0 (0)
2 (20)
Hispanic/Latino ethnicity, n (%)
1 (14.3)
4 (16.7)
2 (40)
1 (10)
Median time from initial diagnosis to first dose (range), years
2.7 (1.6-4.3)
2.5 (0.5-6.1)
0.6 (0.05-5.6)
0.8 (0.5-6)
Median lines of prior systemic therapy (range)
2 (1-10)a
1 (1-1)
1 (1-1)
1 (1-1)
Median time from last progression of prior systemic therapy to first dose (range), days
15 (10-112)
8.5 (4-23)
7 (2-26)
11 (4-25)
Median blast countb (range), %
62 (20-99)
67 (6.7-98)
71 (32.4-96.2)
4 (0-65)
Extramedullary disease, n (%)
0 (0)
4 (16.7)
2 (40)
10 (100)
CNS negative at study entry, n (%)
7 (100)
20 (83.3)
3 (60)
8 (80)
Abbreviations: ALL, acute lymphoblastic leukemia; CNS, central nervous system; LL, lymphoblastic lymphoma.
aTwo patients were listed in error as receiving only 1 prior systemic therapy. Both patients received >1 prior line of treatment; however, access to data entry was terminated after site closure and subsequent database lock, and the data could thus not be corrected.
bTumorous leukemia/lymphoma cells (n [%]) present in the bone marrow as assessed by bone marrow aspirate/biopsy.
Efficacy
  • Overall efficacy outcomes are summarized in Table: Efficacy Outcomes for B-Cell and T-Cell Cohorts.
    • B-cell cohort5:
      • All patients received cycle 1 treatment, and 4 patients continued treatment in cycle 2.
      • All patients discontinued DARZALEX and chemotherapy; reasons for discontinuation were as follows: PD (n=5), death due to PD (n=1), and physician's decision (n=1).
      • No patients achieved CR within 2 treatment cycles.
      • One patient achieved CRi, 3 patients had refractory ALL, and 3 patients experienced PD as their best response.
      • This cohort was closed, and no additional efficacy endpoints were presented.
    • T-cell cohorts5,6:
      • All patients with T-cell ALL/LL were treated in cycle 1, and 18 (75%) pediatric patients with T-cell ALL, 4 (80%) young adult patients with T-cell ALL, and 6 (60%) patients with T-cell LL were treated in cycle 2.
      • Seven pediatric patients with T-cell ALL entered the DARZALEX continuation phase as a bridge to HSCT (1 patient after cycle 1 and 6 patients after cycle 2). One young adult with T-cell ALL also entered after cycle 1, whereas no patient with T-cell LL received DARZALEX continuation.
      • Discontinuation of DARZALEX and backbone chemotherapy was observed in 8 pediatric patients with T-cell ALL (physician decision [n=5], PD [n=2], and death due to an AE of worsened/altered health status [n=1]), 3 young adult patients with T-cell ALL (AE [n=2] and PD [N=1]), and 4 patients with T-cell LL (physician decision [n=2], AE [n=1], and PD [n=1]).
      • Among patients with baseline extramedullary involvement, the best overall responses (all disease areas) were CRi (n=4/4) for pediatric patients with T-cell ALL, CRi (n=1/2) and refractory (n=1/2) for young adult patients with T-cell ALL, and CR (n=2/4) and PD (n=2/4) for patients with T-cell LL.
      • MRD-negativity at any time during treatment was achieved in 11 (45.8%) pediatric patients with T-cell ALL, 1 (20%) young adult patient with T-cell ALL, and 5 (50%) patients with T-cell LL.
      • A total of 18 (75%) pediatric patients with T-cell ALL received allogeneic HSCT. Similarly, 3 young adult patients with T-cell ALL (60%) and 3 patients with T-cell LL (30%) received allogeneic HSCT.
      • The MRD-negativity rate and allogeneic HSCT details are summarized in Table: MRD-Negativity Rates and Summary of Allogeneic HSCT for T-Cell Cohorts.
      • The median and observed 24-month EFS, RFS, and OS rates are summarized in Table: Summary of EFS, RFS, and OS Rates.

Efficacy Outcomes for B-Cell and T-Cell Cohorts5
Parameter, n (%) (90% CIa)
B-Cell ALL
T-Cell ALL
T-Cell LL
(n=10)
Pediatric Patients
(n=7)
Pediatric Patients
(n=24)
Young Adult Patients
(n=5)
Median treatment duration, months (range)
1.2 (0.8-2.3)
2.2 (0.5-2.9)
1.4 (1-2.1)
2.1 (0.8-2.3)
Median follow-up, months (range)
3.2 (1-4.7)
37.5 (0.8-45.7)
31.7 (2.6-31.7)
23 (1.6-25.3)
End of cycle 1
   CR
-
10 (41.7)
(24.6-60.3)b
3 (60)
(18.9-92.4)
3 (30)
(8.7-60.7)
   CRi/PRc
-
4 (16.7)
(5.9-34.2)
1 (20)
(1-65.7)
2 (20)
(3.7-50.7)
   SDc
-
-
-
3 (30)
(8.7-60.7)
   Refractory ALL
-
8 (33.3)
(17.8-52.1)
1 (20)
(1-65.7)
-
   PD
-
0 (0)
0 (0)
2 (20)
(3.7-50.7)
   NE
-
0 (0)
0 (0)
0 (0)
   Assessment not performed
-
2 (8.3)
(1.5-24)
0 (0)
0 (0)
Any time up to the end of cycle 2
   ORR
1 (14.3)
(0.7-52.1)
20 (83.3)
(65.8-94.1)
4 (80)
(34.3-99)
5 (50)
(22.2-77.8)
      CR
0 (0)
12 (50)
(31.9-68.1)
3 (60)
(18.9-92.4)
4 (40)
(15-69.7)
      CRi/PRc
1 (14.3)
(0.7-52.1)
8 (33.3)
(17.8-52.1)
1 (20)
(1-65.7)
1 (10)
(0.5-39.4)
   SDc
-
-
-
3 (30)
(8.7-60.7)
   Refractory ALL
3 (42.9)
(12.9-77.5)
2 (8.3)
(1.5-24)
1 (20)
(1-65.7)
-
   PD
3 (42.9)
(12.9-77.5)
0 (0)
0 (0)
2 (20)
(3.7-50.7)
   NE
0 (0)
0 (0)
0 (0)
0 (0)
   Assessment not performed
0 (0)
2 (8.3)
(1.5-24)
0 (0)
0 (0)
Abbreviations: ALL, acute lymphoblastic leukemia; CI, confidence interval; CR, complete response; CRi, complete response with incomplete hematologic recovery; LL, lymphoblastic lymphoma; NE, not estimable; ORR, overall response rate; PD, progressive disease; PR, partial response; SD, stable disease.
a90% CIs were based on the Clopper-Pearson exact test.
bP=0.153.cPR and SD for patients with T-cell LL only.

MRD-Negativity Rates and Summary of Allogeneic HSCT for T-Cell Cohorts5
Parameter
T-Cell ALL
T-Cell LL
(n=10)a
Pediatric Patients
(n=24)
Young Adult Patients
(n=5)
MRD-negativity ratea, n (%) (90% CIb)
   End of cycle 1c
7 (29.2)
(14.6-47.9)
0 (0)
5 (50)
(22.2-77.8)
   End of cycle 2c
2 (8.3)
(1.5-24)
1 (20)
(1-65.7)
0 (0)
   After treatmentd
1 (4.2)
(0.2-18.3)
0 (0)
0 (0)
   At any time
11 (45.8)
(28.2-64.2)e
1 (20)
(1-65.7)
5 (50)
(22.2-77.8)
Allogeneic HSCT rate, n (%) (90% CIb)
18 (75)
(56.5-88.5)
3 (60)
(18.9-92.4)
3 (30)
(8.7-60.7)
   Median number of CD34+ cells transplanted (range), 106/kg
5.3 (0.5-264)
4.6 (1.2-10)
3.7 (3.2-7.3)
   Source of CD34+ cells transplantedf, n (%)
      Cord blood
2 (11.1)
0 (0)
1 (33.3)
      Peripheral blood
7 (38.9)
2 (66.7)
1 (33.3)
      Bone marrow
9 (50)
1 (33.3)
1 (33.3)
   Median time to engraftment (range), days
18 (10-34)
26 (21-31)
20 (11-23)
Abbreviations: ALL, acute lymphoblastic leukemia; CD, cluster of differentiation; CI, confidence interval; HSCT, hematopoietic stem cell transplant; LL, lymphoblastic lymphoma; MRD, minimal residual disease.
aMRD-negativity rate was calculated with the number of patients who were MRD-negative as the numerator and the number of patients in the all-treated analysis set as the denominator. In the T-cell LL cohort, bone marrow evaluation was only required if bone marrow disease was present at study entry; of the 5 patients with bone marrow involvement (≥5% bone marrow blasts) at baseline, 3 patients achieved MRD-negativity during the study.
b90% CIs were based on the Clopper-Pearson exact test.
cRates in cycle 1 and cycle 2 are mutually exclusive.
dAssessed before the initiation of subsequent treatment and/or HSCT.
eOne patient with pediatric T-cell ALL underwent an unscheduled MRD assessment on day 1 of cycle 3. This patient was included in the count for “at any time” but was not included at the end of cycle 1, at the end of cycle 2, or in posttreatment counts.
fPercentages were calculated with the number of patients who had CD34+ cells sourced from the indicated tissue type as the numerator and the number of patients who underwent allogeneic HSCT as the denominator.

Summary of EFS, RFS, and OS Rates5
Parameter
T-Cell ALL
T-Cell LL
(n=10)
Pediatric Patients
(n=24)
Young Adult Patients
(n=5)
EFS
   Median, months
8.9
10.3
2.9
   24-month observed rate, %
36.1
20
20
RFSa
   Median, months
19.4
9.4
NE
   24-month observed rate, %
48.6
33.3
50
OS
   Median, months (90% CI)
10.9 (6.7-NE)
12 (4.5-NE)
4.2 (1.7-5.6)
   24-month observed rate, %
41.3
25
20
Abbreviations: ALL, acute lymphoblastic leukemia; CR, complete response; CI, confidence interval; EFS, event-free survival; LL, lymphoblastic lymphoma; NE, not estimable; OS, overall survival; RFS, relapse-free survival.aPatients who achieved CR.
Safety
  • No new safety concerns were identified with DARZALEX.5 Any-grade and grade 3/4 TEAEs occurred in all patients (100%) and are summarized in Table: TEAEs in B-Cell and T-Cell Cohorts.
    • The most common grade 3/4 TEAEs across cohorts were hematologic events.
    • Grade 3/4 infections occurred in 1 pediatric patient with B-cell ALL (grade 4 sepsis), 12 (50%) pediatric patients with T-cell ALL, 2 (40%) young adult patients with T-cell ALL, and 3 (30%) patients with T-cell LL.
    • No specific infections occurred in >2 patients across the T-cell cohorts.
    • Serious TEAEs occurred in 3 (42.9%) pediatric patients with B-cell ALL (febrile neutropenia, multiple organ dysfunction syndrome, and respiratory distress [n=1]; febrile neutropenia [n=1]; and febrile neutropenia, sepsis, and death [n=1]), 16 (66.7%) pediatric patients with T-cell ALL, 4 (80%) young adult patients with T-cell ALL, and 7 (70%) patients with T-cell LL. Events in ≥2 patients in the T-cell cohorts included pyrexia, febrile neutropenia, septic shock, hyperbilirubinemia, neutropenia, diarrhea, stomatitis, and cellulitis.
    • DARZALEX discontinuation due to TEAEs occurred in 1 pediatric patient with T-cell ALL (brain edema/hepatic failure), 2 young adult patients with T-cell ALL (hyperbilirubinemia, neutropenia, septic shock, and thrombocytopenia [n=1]; psychotic disorder [n=1]), and 1 patient with T-cell LL (seizure). None of the events were attributed to DARZALEX.
    • Death due to TEAEs was reported in 2 pediatric patients with B-cell ALL (multiorgan dysfunction syndrome [n=1]; unknown cause [n=1]), 2 pediatric patients with T-cell ALL (brain edema/hepatic failure due to backbone chemotherapy [n=1]; worsened or altered general health status [n=1]), and 1 patient with T-cell LL (pleural effusion). None of the deaths were attributed to DARZALEX.
    • IRRs after the first DARZALEX infusion were reported in 4 (57.1%) pediatric patients with B-cell ALL, 16 (66.7%) pediatric patients with T-cell ALL, 4 (80%) young adult patients with T-cell ALL, and 8 (80%) patients with T-cell LL.
      • The most common IRRs were cough (42.9%) in pediatric patients with B-cell ALL; abdominal pain (20.7%), vomiting (13.8%), and pyrexia (13.8%) in patients with T-cell ALL; and cough (40%) and dyspnea (30%) in patients with T-cell LL.
    • Throughout the study, none of the 36 evaluable patients tested positive for anti-DARZALEX antibodies.

TEAEs in B-Cell and T-Cell Cohorts5
TEAE, n (%)
B-Cell ALL
T-Cell ALL
T-Cell LL
(n=10)
Pediatric Patients
(n=7)
Pediatric Patients
(n=24)
Young Adult Patients
(n=5)
Any-grade TEAE
7 (100)
24 (100)
5 (100)
10 (100)
Any-grade TEAEs in >50% of patients in any cohort
   Febrile neutropenia
5 (71.4)
12 (50)
3 (60)
6 (60)
   Anemia
4 (57.1)
16 (66.7)
2 (40)
10 (100)
   Thrombocytopenia
2 (28.6)
18 (75)
3 (60)
9 (90)
   Neutropenia
2 (28.6)
15 (62.5)
2 (40)
6 (60)
   Leukopenia
3 (42.9)
9 (37.5)
1 (20)
5 (50)
   Vomiting
2 (28.6)
15 (62.5)
2 (40)
5 (50)
   Abdominal pain
2 (28.6)
12 (50)
3 (60)
4 (40)
   Stomatitis
0 (0)
11 (45.8)
3 (60)
7 (70)
   Constipation
2 (28.6)
6 (25)
4 (80)
2 (20)
   Pyrexia
4 (57.1)
17 (70.8)
3 (60)
8 (80)
   Fatigue
0 (0)
3 (12.5)
3 (60)
1 (10)
   Hyperbilirubinemia
0 (0)
8 (33.3)
4 (80)
4 (40)
   ALT increased
3 (42.9)
10 (41.7)
3 (60)
5 (50)
   AST increased
2 (28.6)
5 (20.8)
3 (60)
5 (50)
   Blood AP increased
0 (0)
0 (0)
4 (80)
0 (0)
   Hypoalbuminemia
0 (0)
12 (50)
3 (60)
5 (50)
   Hyponatremia
0 (0)
6 (25)
4 (80)
2 (20)
   Cough
3 (42.9)
7 (29.2)
0 (0)
5 (50)
   Hypoxia
2 (28.6)
4 (16.7)
3 (60)
0 (0)
Grade 3/4 TEAE
7 (100)
24 (100)
5 (100)
10 (100)
Grade 3/4 TEAEs in >40% of patients in any cohort
   Febrile neutropenia
5 (71.4)
12 (50)
3 (60)
5 (50)
   Anemia
3 (42.9)
16 (66.7)
1 (20)
10 (100)
   Leukopenia
3 (42.9)
9 (37.5)
1 (20)
5 (50)
   Neutropenia
2 (28.6)
15 (62.5)
2 (40)
6 (60)
   Thrombocytopenia
1 (14.3)
15 (62.5)
3 (60)
9 (90)
Serious TEAE
3 (42.9)
16 (66.7)
4 (80)
7 (70)
TEAE leading to DARZALEX discontinuation
0 (0)
1 (4.2)
2 (40)
1 (10)
Death due to TEAEs
2 (28.6)
2 (8.3)
0 (0)
1 (10)
IRRs
   Grade 1/2
4 (57.1)
15 (62.5)
4 (80)
7 (70)
   Grade 3
0 (0)
1 (4.2)
0 (0)
1 (10)
Abbreviations: ALL, acute lymphoblastic leukemia; ALT, alanine aminotransferase; AP, alkaline phosphatase; AST, aspartate aminotransferase; IRR, infusion-related reaction; LL, lymphoblastic lymphoma; TEAE, treatment-emergent adverse event.
Pharmacokinetics
  • B-cell cohort6:
    • The mean peak serum concentration for daratumumab showed an increase of approximately 1.64-fold from 302 μg/mL (SD, 83.1) on day 1 of cycle 1 at end of infusion (EOI) to 494 μg/mL (SD, 184) on day 1 of cycle 2 at EOI, indicating accumulation after weekly daratumumab administration.
    • The mean serum daratumumab concentration at the end of treatment was 58.9 μg/mL (SD, 50.7), which decreased to 11.5 μg/mL (SD, 6.06) by post-treatment week 8.
    • Overall, the serum daratumumab concentrations observed in the B-cell ALL cohort were comparable to those seen in adult patients with multiple myeloma.
    • After weekly administration of daratumumab, the mean cerebrospinal fluid concentration was 0.573 μg/mL (SD, 0.545) on day 1 of cycle 2 prior to dosing, significantly lower than the corresponding serum concentration, indicating no drug accumulation in the cerebrospinal fluid.
  • T-cell cohorts5:
    • In pediatric patients with T-cell ALL, the mean peak serum concentration for daratumumab showed an increase of approximately 2.9-fold from 263 μg/mL (SD, 8.18) on day 1 of cycle 1 at EOI to 763 μg/mL (SD, 185) on day 22 of cycle 2 at EOI, indicating accumulation after weekly daratumumab administration.
      • The mean Ctrough prior to dosing in pediatric patients with T-cell ALL was 324 μg/mL (SD, 184) and 369 μg/mL (SD, 105) on days 1 and 22 of cycle 2, respectively.
      • Comparable results were obtained in the young adult T-cell ALL and T-cell LL cohorts.
    • All but 1 pediatric patient with T-cell ALL provided a postbaseline CSF PK sample, resulting in a CSF PK-evaluable population of 38 patients.
      • The daratumumab CSF concentration was similar in both the pediatric T-cell ALL and T-cell LL cohorts.
      • Among young adults with T-cell ALL, a lower daratumumab CSF concentration was observed over time.
      • The mean CSF concentration in pediatric patients with T-cell ALL was 0.907 μg/mL (SD, 1.96) on day 15 of cycle 1 before dosing and 0.934 μg/mL (SD, 0.549) on day 15 of cycle 2 before dose.

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 04 February 2025. For streamlining purposes, retrospective-analyses, systematic reviews, review articles, and case reports have been excluded.

In response to your specific request, summarized in this response is the relevant data from company-sponsored studies pertaining to this topic.

References

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1 Data on File. Daratumumab Intravenous Formulation Company Core Data Sheet (CCDS). Janssen Research & Development, LLC. EDMS-ERI-78724630; 2024.  
2 Data on File. Daratumumab Subcutaneous Formulation Company Core Data Sheet (CCDS). Janssen Research & Development, LLC. EDMS-ERI-184804517; 2025.  
3 Janssen Research & Development, LLC. A study to evaluate the efficacy and safety of daratumumab in pediatric and young adult participants greater than or equal to 1 and less than or equal to 30 years of age with relapsed/refractory precursor B-cell or T-cell acute lymphoblastic leukemia or lymphoblastic lymphoma. In: clinicaltrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 4 February 2025]. Available from: https://www.clinicaltrials.gov/ct2/show/NCT03384654?term=NCT03384654&rank=1 NLM Identifier: NCT03384654.  
4 Hogan L, Bhatla T, Teachey D, et al. Efficacy and safety of daratumumab (DARA) in pediatric and young adult patients with relapsed/refractory T-cell acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL): initial results from the phase 2 DELPHINUS study. 2022;(Oral Presentation).  
5 Bhatla T, Hogan LE, Teachey DT, et al. Daratumumab in pediatric relapsed/refractory acute lymphoblastic leukemia or lymphoblastic lymphoma: the DELPHINUS study. Blood. 2024;144(21):2237-2247.  
6 Bhatla T, Hogan LE, Teachey DT, et al. Supplement to: Daratumumab in pediatric relapsed/refractory acute lymphoblastic leukemia or lymphoblastic lymphoma: the DELPHINUS study. Blood. 2024;144:2237-2247.