CARVYKTI®
(ciltacabtagene autoleucel)
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CARVYKTI® (ciltacabtagene autoleucel)
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CARVYKTI - Use of Anakinra in the Management of Cytokine Release Syndrome in CARTITUDE-1
Last Updated: 02/19/2025
Summary
- CARTITUDE-1 (MMY2001) was a phase 1b/2 study evaluating the safety and efficacy of CARVYKTI in patients with relapsed/refractory multiple myeloma (RRMM) who had previously received a proteasome inhibitor (PI), an immunomodulatory agent, and an antiCD38 antibody.1
, 2 - Cytokine release syndrome (CRS) has been reported as an adverse event in the CARTITUDE-1 study.
Per study protocol, CRS was managed with tocilizumab or tocilizumab plus steroids; patients not responding to these treatments could be given other anticytokine therapy (eg, anakinra) at the discretion of the investigator.3 Institutional experiences of anakinra use in the management of CRS in patients who received CARVYKTI as part of the CARTITUDE-1 study were evaluated.1- 3 In CARTITUDE-1, CRS occurred in 95% of patients (n=92), with grade 3/4 CRS occurring in 4% of patients and grade 5 CRS occurring in 1 patient. The median time to onset of CRS was 7 days (range, 1-12).1-3 - Overall, 91% of patients (n=88) were administered supportive measures to treat CRS (tocilizumab, 69%; corticosteroids, 22%; anakinra, 19%).1,3
- Patients were given anakinra when tocilizumab did not effectively manage CRS.3
CRS resolved after a median of 5 days (range, 2-10) in patients who received anakinra and tocilizumab with steroids (n=14) or without steroids (n=4).3 Median duration of CRS was 4 days (range 1-14) and CRS resolved in 99% of patients (n=91). 1,3 - No new events of CRS (no changes in the incidence, time to onset, or duration) have occurred since the median 12.4-month follow-up.1
Institutional experiences of anakinra use in the management of CRS in patients who received CARVYKTI as part of the CARTITUDE-1 study were evaluated.3
Study Design/Methods
- Key eligibility criteria: adult patients with progressive MM per International Myeloma Working Group (IMWG) criteria; Eastern Cooperative Oncology Group performance status (ECOG PS) ≤1; measurable disease; received ≥3 prior lines of therapy or double refractory; prior PI, immunomodulatory drug, and anti-CD38 therapy.1,2
- Dosing: patients received a single infusion of CARVYKTI at a target dose of 0.75×106
chimeric antigen receptor (CAR)+ T cells/kg (target range 0.5-1.0×106) 57 days after the start of lymphodepletion (cyclophosphamide 300 mg/m2 and fludarabine 30 mg/m2 given daily for 3 days on days -5 to -3).1,2 - Primary endpoints for phase 1b: evaluate the safety and confirm the recommended phase 2 dose.2
- Primary endpoint for phase 2: evaluate the efficacy of CARVYKTI by overall response rate (ORR).2
Results
Overall, of the 113 patients enrolled/apheresed, 101 patients were lymphodepleted and 97 patients were treated with CARVYKTI in the combined phase 1b/2 study.2 - Prior to lymphodepletion, a total of 12 patients discontinued participation in the study (progressive disease, n=2; withdrawal by patient, n=2; deaths, n=8). Prior to CARVYKTI infusion, 3 patients withdrew from treatment, and 1 patient died.2
- Patients received a median of 6 prior lines of therapy, 88% of patients were tripleclass refractory, 42% of patients were penta-drug refractory, and 99% of patients were refractory to last line of therapy.2
Safety - Adverse Events - CRS
- The incidence, timing/duration, and management of CRS are presented in Table: CARTITUDE-1: CRS.
- Anakinra was administered in patients for whom tocilizumab did not effectively manage CRS.3 Use of anakinra per study patient with CRS event is presented in Table: CARTITUDE-1: Use of Anakinra Per Study Patient with CRS Event.
- CRS resolved after a median of 5 days (range, 2-10) in patients who received anakinra and tocilizumab with steroids (n=14) or without steroids (n=4).3
- One patient died due to hemophagocytic lymphohistiocytosis (HLH) considered related to study treatment.2
- No new events of CRS (no changes in the incidence, time to onset, or duration) occurred since the 12.4-month median follow-up.2
| Total (N=97) | |
|---|---|
| Patients with CRS, n (%) | |
| Any gradea | 92 (94.8) |
| Grade 3/4 | 4 (4.1) |
| Grade 5 | 1 (1) |
| Median time to onset of CRS, days (IQR) | 7 (5-8) |
| CRS onset day 4 or later, n (%) | 82 (89) |
| CRS onset day 6 or later, n (%) | 68 (74) |
| Median duration of CRS, days (IQR) | 4 (3-6)b |
| CRS resolved within 14 days of onset, n (%) | 91 (99) |
| Supportive measures, n (%) | 88 (91) |
| Tocilizumab | 67 (69)c |
| Corticosteroids | 21 (22) |
| Anakinra | 18 (19) |
| Vasopressor used | 4 (4) |
| Intubation/mechanical ventilation | 1 (1) |
| Cyclophosphamide | 1 (1) |
| Etanercept | 1 (1) |
| Abbreviations: ASTCT, American Society for Transplantation and Cellular Therapy; CRS, cytokine release syndrome; HLH, aCRS was graded using Lee et al (Blood 2014) in the phase 1b portion of the study and ASTCT in phase 2; in this combined analysis, Lee et al criteria were mapped to 2019 ASTCT criteria for patients in the phase 1b portion. bOne patient with 97-day duration died due to CRS/HLH. cFour patients received ≥3 doses. | |
| Onset of CRS, Day Post CARVYKTI Infusion | CRS Duration, Days | Maximum CRS Toxicity Gradea | Initiation of Anakinra, Day After Onset of CRS | Cumulative Anakinra Use, Days | |
|---|---|---|---|---|---|
| 1b | 8 | 2 | 1 | 1 | 2 |
| 2 | 3 | 97 | 5 | 6 | 15 |
| 3 | 7 | 4 | 1 | 1 | 3 |
| 4 | 5 | 4 | 2 | 2 | 3 |
| 5 | 9 | 3 | 2 | 2 | 3 |
| 6 | 7 | 6 | 1 | 1 | 2 |
| 7 | 9 | 6 | 3 | 3 | 5 |
| 8 | 2 | 6 | 1 | 4 | 2 |
| 9 | 8 | 7 | 1 | 3 | 5 |
| 10b | 7 | 6 | 1 | 2 | 7 |
| 11 | 5 | 10 | 3 | 2 | 9 |
| 12 | 4 | 5 | 2 | 4 | 1 |
| 13 | 6 | 10 | 2 | 3 | 2 |
| 14b | 2 | 7 | 1 | 5 | 2 |
| 15b | 6 | 5 | 2 | 3 | 4 |
| 16 | 6 | 5 | 2 | 3 | 1 |
| 17 | 7 | 5 | 2 | 2 | 1 |
| 18 | 5 | 5 | 2 | 3 | 1 |
| Abbreviations: ASTCT, American Society for Transplantation and Cellular Therapy; CRS, cytokine release syndrome. aCRS was graded using Lee et al (Blood 2014) in the phase 1b portion of the study and ASTCT in phase 2; in this combined analysis, Lee et al criteria were mapped to 2019 ASTCT criteria for patients in the phase 1b portion. bPatients received only anakinra and tocilizumab; all other patients received anakinra, tocilizumab, and steroids. | |||||
LITERATURE SEARCH
A literature search of MEDLINE®
References
| 1 | Berdeja JG, Madduri D, Usmani SZ, et al. Ciltacabtagene autoleucel, a B-cell maturation antigen directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study. Lancet. 2021;398(10297):314-324. |
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