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CARVYKTI®

(ciltacabtagene autoleucel)

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This information is intended for US healthcare professionals to access current scientific information about J&J Innovative Medicine products. It is prepared by Medical Information and is not intended for promotional purposes, nor to provide medical advice.

CARVYKTI® (ciltacabtagene autoleucel)

Medical Information

CARVYKTI - Adverse Event - Mortality

Last Updated: 11/14/2025

SUMMARY

  • Janssen does not recommend the use of CARVYKTI in a manner that is inconsistent with the approved labeling.
  • CARTITUDE-1 is a phase 1b/2, open label, multicenter study of CARVYKTI in patients with relapsed or refractory multiple myeloma (RRMM) after ≥ 3 prior lines of therapy (LOT) including a proteasome inhibitor (PI), an immunomodulatory drug, and an anti-CD38 monoclonal antibody (mAb).1-3
    • Lin Y et al (2023)3 reported that, at a median follow-up of 29.9 months post-CARVYKTI infusion (N=97), 35 deaths occurred: 6 were treatment-related adverse events [AEs], 12 were due to unrelated AEs, and 17 resulted from progressive disease.
  • CARTITUDE-2 is a phase 2, open-label, multicohort, single-arm, multicenter study evaluating CARVYKTI in patients with multiple myeloma (MM) in various clinical settings.4
    • Cohort A evaluates patients with RRMM who received 1-3 prior LOT and are refractory to lenalidomide.5-8
      • Cohen et al (2024)9 reported that, at a median follow-up of 15.6 months, 1 treatment-related death occurred after CARVYKTI infusion (sepsis, diagnosed on day 30)
      • Hillengas et al (2023) reported that, at a median follow-up of 29.9 months, 5 deaths had occurred after CARVYKTI infusion. The reasons for death were as follows: progressive disease (n=3; day 426, day 550, and day 666), sepsis (n=1; not treatment related; day 394), and pneumonia (n=1; also had an AE of sepsis in addition to coronavirus disease 2019 (COVID-19) pneumonia and was treatment related; day 100).7
    • Cohort B evaluates patients with early relapse (≤12 months after frontline therapy or ≤12 months after autologous stem cell transplant [ASCT]).10-12
      • Hillengas et al (2023)7 reported that, at a median follow-up of 27.9 months, 4 deaths had occurred after CARVYKTI infusion. The reasons for death were as follows: progressive disease (n=3) and cardiac arrest (n=1).
    • Cohort C evaluates patients with RRMM with prior exposure to a PI, immunomodulatory drug, and an anti-CD38 mAb, and a B-cell maturation antigen (BCMA) bispecific antibody (BsAb) or antibody-drug conjugate (ADC).13,14
      • Cohen et al (2022)14 reported that, at a median follow-up of 18 months, a total of 12 deaths had occurred after CARVYKTI infusion. Of these, 7 occurred in the ADC-exposed group and 5 in the BsAb-exposed group.
    • Cohort D evaluates patients with RRMM who achieved less than a complete response (<CR) after frontline ASCT, with or without lenalidomide maintenance.4,15
      • Arnulf et al (2024)15 reported that, at a median follow-up of 22.4 months, no deaths due to treatment-emergent adverse events (TEAEs) were reported.
  • CARTITUDE-4 is a phase 3, open-label, multicenter study evaluating CARVYKTI versus standard care regimens, DARZALEX FASPRO (daratumumab and hyaluronidase), pomalidomide, and dexamethasone (DPd) or pomalidomide, bortezomib, and dexamethasone (PVd), in patients with RRMM who received 1-3 prior LOT, including a proteasome inhibitor and an immunomodulatory drug, and are refractory to lenalidomide.16,17
    • Costa et al (2024)18 reported that, at a median follow-up of 15.9 months among patients who received 1 prior LOT, 11 patients in each of the CARVYKTI and standard care arms died. Of these patients, 7 patients in the CARVYKTI arm and 9 patients in the standard care arm had functionally high-risk MM.
    • Mateos et al (2024)17 reported that, at a median follow-up of 33.6 months, 50 CARVYKTI patients and 82 standard care patients had died in the safety population (N=208 per group).
    • San-Miguel et al (2023)16 reported that, at a median follow-up of 15.9 months, 18.8% of CARVYKTI patients and 22.1% of standard care patients had died in the safety population (N=208 per group).
  • The Food and Drug Administration Oncologic Drugs Advisory Committee (ODAC) reviewed the overall survival data and the risk and benefit of CARVYKTI from the CARTITUDE-4 clinical trial in March 2024.19

PRODUCT LABELING

clinical data - Cartitude-1 - Phase 1B/2 STUDY

CARTITUDE-1 (MMY2001;NCT03548207) was a phase 1b/2, open-label study evaluating the efficacy and safety of CARVYKTI in patients with RRMM after ≥3 prior LOT including a PI, an immunomodulatory drug, and an anti-CD38 mAb.1-3

  • Treatment arm: CARVYKTI (single arm)
  • Key eligibility criteria:3,20,21
    • Progressive MM per International Myeloma Working Group (IMWG) criteria
    • ≥3 prior LOTs or double refractory to a PI and an immunomodulatory drug
    • Prior exposure to a PI, an immunomodulatory drug, and an anti-CD38 mAb
    • No prior exposure to CAR-T or BCMA targeting therapy
  • Primary endpoints: Recommended Phase 2 Dose (RP2D), Overall Response Rate (ORR).3,20,21

Lin et al (2023)3 reported the incidence and causes of death at a median follow-up of 33.4 months (range: 1.5–45.2 months).

  • A total of 35 deaths had occurred during the study.3 Study deaths are presented in Table: CARTITUDE-1: Deaths.
    • A total of 5 new deaths, unrelated to CARVYKTI were reported since the 27.7-month follow-up, including progressive disease (n=3), pneumonia (n=1) and sepsis (n=1).3

CARTITUDE-1: Deaths3
Deaths, n
Total (N=97)
Time of Death Post CARVYKTI Infusion (Days)
Total deaths during the study
35
45-980
Due to progressive disease
17
253-980
AEs unrelated to treatment (n=12)
     Pneumonia
2
109, 887
     AMLa
3
418, 582, 718
     Ascitesb
1
445
     MDS
1
803
     Respiratory failure
3
733, 793, 829
     Septic Shock and/or sepsis
2
917, 945
AEs related to treatment (n=6)
     Sepsis and/or septic shock
2
45, 162
     CRS/HLH
1
99
     Lung abscess
1
119
     Respiratory failure
1
121
     Neurotoxicity
1
247
Abbreviations: AE, adverse event; AML, acute myeloid leukemia; CRS, cytokine release syndrome; HLH, hemophagocytic lymphohistiocytosis; MDS, myelodysplastic syndrome.
aOne patient with AML also had MDS and a cytogenetic profile consistent with MDS (del20q [present before CARVYKTI infusion], loss of 5q); another patient who died from AML had both prostate cancer and squamous cell carcinoma of the scalp.
bPatient died from ascites (unrelated to CARVYKTI as assessed by the investigator) due to noncirrhotic portal fibrosis and non-alcoholic steatosis that was present for many years preceding the study.

clinical data - CARTITUDE-2 - PHASE 2 STUDY

CARTITUDE-2 (MMY2003; NCT04133636) is an ongoing, phase 2, open-label, multicohort, single-arm, multicenter study evaluating the efficacy and safety of CARVYKTI in patients with MM in various clinical settings.4

Study Design/Methods

  • Treatment arm: CARVYKTI (single arm)
  • Key eligibility criteria:
    • No prior CAR-T cell therapy (Cohorts A-D) or BCMA-targeted therapy (Cohorts A, B, D)
    • Cohort A: 1-3 prior LOTs, including a PI and an immunomodulatory drug; lenalidomide refractory.4
    • Cohort B: 1 prior LOT, including a PI and an immunomodulatory drug; disease progression ≤12 months after ASCT or ≤12 months from other antimyeloma therapy.4
    • Cohort C: Previously treated with a PI, an immunomodulatory drug, an anti-CD38 mAb, and BCMA BsAb or ADC.4,13
    • Cohort D: History of 4-8 cycles of initial therapy, including induction, high-dose chemotherapy, and ASCT with or without consolidation, in patients with <CR after frontline ASCT.8,15
  • Primary endpoints: Minimal residual disease (MRD) negativity at the 10-5 sensitivity level defined by IMWG criteria (assessed by next-generation sequencing or next-generation flow).5,12,14

Cohort A

Hillengas et al (2023) reported that, at a median follow-up of 29.9 months(range, 3.3-35.6), 5 deaths had occurred after CARVYKTI infusion. The reasons for death were as follows: progressive disease (n=3; day 426, day 550, and day 666), sepsis (n=1; not treatment related; day 394), and pneumonia (n=1; also had an AE of sepsis in addition to coronavirus disease 2019 (COVID-19) pneumonia and was treatment related; day 100).7

Cohen et al (2024)9 reported that, at a median follow-up of 15.6 months (range, 1.0-29.2), 1 treatment-related death occurred after CARVYKTI infusion (sepsis, diagnosed on day 30)

Cohort B

Hillengas et al (2023)7 reported that, at a median follow-up of 27.9 months (range, 5.2-32.1), 4 deaths had occurred after CARVYKTI infusion. The reasons for death were as follows: progressive disease (n=3) and cardiac arrest (n=1; new event since the last data cutoff and was not treatment related).

Cohort C

Cohen et al (2022)14 reported that, at a median follow-up of 18 months (range, 0.622.7), 12 deaths had occurred after CARVYKTI infusion. Complete details can be found in Table: CARTITUDE-2 (Cohort C): Deaths.

  • A total of 7 deaths occurred in the ADC-exposed group due to progressive disease (n=6) and COVID-19 pneumonia (n=1; not treatment related).  
  • A total of 5 deaths occurred in the BsAb-exposed group due to progressive disease (n=2), COVID-19 pneumonia (n=1; not treatment related), Clostridium difficile colitis (n=1; treatment related), subarachnoid hemorrhage (n=1; not treatment related).

CARTITUDE-2 (Cohort C): Deaths14
Patient Group
Cause of Death
Study Day of Death
Duration of Last Anti-BCMA Agent (Days)
Time From Last Anti-BCMA Agent to CARVYKTI Infusion (Days)
Prior ADC
Progressive diseasea
60
34
95
Progressive diseasea
254
64
116
Progressive disease
327
21
749
COVID-19 pneumonia (not treatment related)b
378
277
271
Progressive disease
639
527
944
Progressive disease
690
23
243
Progressive disease
286
22
177
Prior BsAb
C. difficile colitis (treatment related)c
17
130
124
COVID-19 pneumonia (not treatment related)a
161
71
227
Subarachnoid hemorrhage (not treatment related)
64
29
307
Progressive disease
401
36
325
Progressive disease
486
23
84
Abbreviations: ADC, antibody-drug conjugate; BCMA, B-cell maturation antigen; BsAb, bispecific antibody; C. difficile, Clostridium difficile; COVID-19, coronavirus disease 2019; ICANS, immune effector cell-associated neurotoxicity syndrome.
aPatient received anti-BCMA agent as last line of therapy.
bPatient received both doses of the Moderna COVID-19 vaccine.
cPatient with ICANS that did not recover. Patient had several other severe conditions, including C. difficile colitis, kidney failure, respiratory failure, and hemophagocytic lymphohistiocytosis. This patient died on day 17 from C. difficile colitis.

Cohort D

Arnulf et al (2024)15 reported that, at a median follow-up of 22.4 months (range, 4.7-39.3), no deaths due to TEAEs were reported.

CLINICAL DATA - CARTITUDE-4 - PHASE 3 STUDY

CARTITUDE-4 (MMY3002; NCT04181827) is a 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.16

Study Design/Methods

  • Treatment arms: Randomized 1:1 to receive either CARVYKTI or standard care (PVd or DPd)
  • Key eligibility criteria
    • Received 1-3 prior lines of therapy including a PI and an immunomodulatory drug
    • Refractory to lenalidomide
    • No prior exposure to CAR-T or BCMA targeting therapy
  • Primary endpoint: PFS

Costa et al (2024)18 reported that, at a median follow-up of 15.9 months (range, 0.1-27.3), among patients who received 1 prior LOT, 11 patients in each of the CARVYKTI and standard care arms died. Of these, 7 patients in the CARVYKTI arm and 9 patients in the standard care arm had functionally high-risk MM.

    • Among the 7 patients that died in the CARVYKTI arm, death occurred in 2 patients that did not receive CARVYKTI as study treatment and in 3 patients that received CARVYKTI as subsequent therapy.18

Mateos et al (2024)17 reported that, 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.

CARTITUDE-4: Deaths (Median Follow-up of 33.6 Months)17

CARVYKTI
(n=208)
Standard Care
(n=208)
Deaths, n
50
82
   Due to Progressive Disease, n
21
51
   Due to TEAE, n
12
8
   Deaths due to TE and non-TE infections, n
16
19
       In the first year, n
13
8
       In the second year, n
2
8
Abbreviations: TE, treatment-emergent; TEAE, treatment-emergent adverse event.

San-Miguel et al (2023)16 published the primary efficacy and safety results from the CARTITUDE-4 study, based on a median follow-up of 15.9 months (range, 0.1-27.3).

  • A total of 39 CARVYKTI patients (18.8%) and 46 standard care patients (22.1%) in the safety population died (one patient in the standard care group died prior to treatment).
  • Of the 39 CARVYKTI patients who died, 6.7% died due to progressive disease, 7.2% died due to non-TEAE, and 4.8% died due to TEAEs.16,22
    • COVID-19 pneumonia had the highest cause of death (3.4%) among patients who died from a treatment-emergent AE. The other causes of death from the CARVYKTI arm: neutropenic sepsis, pneumonia, respiratory failure.
  • Of the 46 standard care patients who died, 14.4% died due to progressive disease, 5.3% died due to non-TEAE, and 2.4% died due to TEAEs.16,22
    • The cause of death among patients who died due to a TEAE was the same (0.5%) for COVID-19 pneumonia, progressive multifocal leukoencephalopathy, respiratory tract infection, septic shock, and pulmonary embolism.

CARTITUDE-4 (ONCOLOGY DRUGS ADVISORY COMMITTEE)

  • The Food and Drug Administration Oncologic Drugs Advisory Committee (ODAC) reviews and evaluates data regarding the safety and efficacy of marketed and investigational human drug products used in the treatment of cancer and makes appropriate recommendations to the Commissioner of Food and Drugs.23
  • In March 2024, the ODAC reviewed the overall survival data and the risk and benefit of CARVYKTI from the CARTITUDE-4 clinical trial.19

CARTITUDE-4: Total Deaths and Causes of Deaths at 0-≤3 and >3-≤6 Months (ITT Analysis Set)19
Cause of Death
0-≤3 Months
>3-≤6 Months
Never Treated With CARVYKTI (n=12)
CARVYKTI as Subsequent Therapy (n=20)
CARVYKTI as Study Treatment (n=176)
Standard Care
(n=211)
Never Treated with CARVYKTI (n=12)
CARVYKTI as Subsequent Therapy (n=20)
CARVYKTI as Study Treatment (n=176)
Standard Care (n=211)
Total Deaths
6
1
0
1
3
4
4
11
   PD
4
-
-
1
3
-
1
5
   AEs
2a
1b
-
-
-
4c
3d
6e
Abbreviations: AE, adverse event; COVID-19, coronavirus disease 2019; ITT, intent-to-treat; PD, progressive disease.
aRespiratory failure (n=1), gastrointestinal hemorrhage (n=1).
bRetroperitoneal hemorrhage (n=1), Pseudomonal sepsis.
cCerebral haemorrhage (n=1), bronchopulmonary aspergillosis (n=1), sepsis (n=1), pseudomonal sepsis (n=1).
dAll 3 due to COVID-19 pneumonia.
eCOVID-19 pneumonia (n=1), pneumocystis jirovecii pneumonia (n=1), pneumonia influenza (n=1), progressive multifocal leukoencephalopathy (n=1), respiratory tract infection (n=1), multiple organ dysfunction syndrome (n=1).

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 13 November 2025.

 

References

Show
1 Martin T, Usmani SZ, Berdeja JG, et al. Ciltacabtagene autoleucel, an anti-B-cell maturation antigen chimeric antigen receptor T-cell therapy, for relapsed/refractory multiple myeloma: CARTITUDE-1 2-year follow-up. J Clin Oncol. 2022;41(6):1265-1274.  
2 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.  
3 Lin Y, Martin G, Usmani SZ, et al. CARTITUDE-1 final results: phase 1b/2 study of ciltacabtagene autoleucel in heavily pretreated patients with relapsed/refractory multiple myeloma. Oral presentation presented at: American Society of Clinical Oncology (ASCO) Annual Meeting; June 2-6, 2023; Chicago, IL/Virtual.  
4 Janssen Research & Development, LLC. A study of JNJ-68284528, a chimeric antigen receptor t cell (CAR-T) therapy directed against b-cell maturation antigen (BCMA) in participants with multiple myeloma (CARTITUDE-2). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2025 November 13]. Available from: https://clinicaltrials.gov/ct2/show/NCT04133636 NLM Identifier: NCT04133636.  
5 Einsele H, Cohen A, Delforge M, et al. Biological correlative analyses and updated clinical data of ciltacabtagene autoleucel, a BCMA-directed CAR-T cell therapy, in lenalidomide-refractory patients with progressive multiple myeloma after 1-3 prior lines of therapy: CARTITUDE-2, Cohort A. Poster presented at: American Society of Clinical Oncology (ASCO) Annual Meeting; June 3-7, 2022; Chicago, IL/Virtual.  
6 Agha M, Cohen A, Madduri D, et al. CARTITUDE-2: efficacy and safety of ciltacabtagene autoleucel, a BCMA-directed CAR T-cell therapy, in patients with progressive multiple myeloma after 1–3 prior lines of therapy. Poster presented at: American Society of Clinical Oncology (ASCO) Annual Meeting; June 4-8, 2021; Virtual.  
7 Hillengass J, Cohen AD, Agha M, et al. The phase 2 CARTITUDE-2 trial: updated efficacy and safety of ciltacabtagene autoleucel in patients with multiple myeloma and 1–3 prior lines of therapy (cohort A) and with early relapse after first line treatment (cohort B). Oral Presentation presented at: 65th American Society of Hematology (ASH) Annual Meeting and Exposition; December 9-12, 2023; San Diego, CA.  
8 Cohen Y, Cohen A, Delforge M, et al. Efficacy and safety of ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy, in lenalidomide-refractory patients with progressive multiple myeloma after 1-3 prior lines of therapy: updated results from CARTITUDE-2. Poster presented at: 63rd American Society of Hematology (ASH) Annual Meeting & Exposition; December 11-14, 2021; Atlanta, GA/Virtual.  
9 Cohen A, Voorhees P, Martin T, et al. Ciltacabtagene autoleucel in patients with lenalidomide-refractory multiple myeloma: CARTITUDE-2 cohort A expansion subgroup. Poster presented at: American Society of Clinical Oncology; May 30 - June 4, 2024; Chicago, IL.  
10 Van de Donk NCWJ, Delforge M, Agha M, et al. CARTITUDE-2: Efficacy and safety of ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T cell therapy, in patients with multiple myeloma and early relapse after initial therapy. Poster presented at: 63rd American Society of Hematology (ASH) Annual Meeting & Exposition; December 11-14, 2021; Atlanta, GA/Virtual.  
11 van de Donk NWCJ, Agha M, Cohen A, et al. Biological correlative analyses and updated clinical data of ciltacabtagene autoleucel, a BCMA-directed CAR-T cell therapy, in patients with multiple myeloma and early relapse after initial therapy: CARTITUDE-2, Cohort B. Poster presented at: American Society of Clinical Oncology (ASCO) Annual Meeting; June 3-7, 2022; Chicago, IL/Virtual.  
12 van de Donk NWCJ, Agha M, Cohen A, et al. Ciltacabtagene autoleucel (cilta-cel), a BCMA-directed CAR-T cell therapy, in patients with multiple myeloma (MM) and early relapse after initial therapy: CARTITUDE-2 cohort B 18-month follow-up. Poster presented at: 64th American Society of Hematology (ASH) Annual Meeting; December 10-13, 2022; New Orleans, LA/Virtual.  
13 Cohen A, Mateos M, Cohen Y, et al. Efficacy and safety of cilta-cel in patients with progressive MM after exposure to other BCMA-targeting agents. Blood. 2023;141(3):219-230.  
14 Cohen AD, Mateos MV, Cohen Y, et al. Efficacy and safety of cilta-cel in patients with progressive multiple myeloma after exposure to non-cellular anti-BCMA immunotherapy. Poster presented at: 64th American Society of Hematology (ASH) Annual Meeting; December 10-13, 2022; New Orleans, LA/Virtual.  
15 Arnulf B, Kerre T, Agha M, et al. Efficacy and safety of ciltacabtagene autoleucel ± lenalidomide maintenance in newly diagnosed multiple myeloma with suboptimal response to frontline autologous stem cell transplant: CARTITUDE-2 Cohort D. Oral Presentation presented at: The American Society of Clinical Oncology (ASCO) Annual Meeting; May 31–June 4, 2024; Chicago, IL.  
16 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.  
17 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.  
18 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.  
19 Administration UF and D, Administration F and D, US. March 15, 2024: Meeting of the Oncologic Drugs Advisory Committee Meeting Announcement; 2024. 21 July 2024. https://www.fda.gov/advisory-committees/advisory-committee-calendar/march-15-2024-meeting-oncologic-drugs-advisory-committee-meeting-announcement-03152024
20 Martin T, Usmani SZ, Berdeja JG, et al. Updated results from CARTITUDE-1: phase 1b/2 study of ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T cell therapy, in patients with relapsed/refractory multiple myeloma. Oral presentation presented at: 63rd American Society of Hematology (ASH) Annual Meeting & Exposition; December 11-14, 2021; Atlanta, GA/Virtual.  
21 Madduri D, Berdeja JG, Usmani SZ, et al. CARTITUDE-1: phase 1b/2 study of ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy, in relapsed/refractory multiple myeloma. Oral presentation presented at: 62nd American Society of Hematology (ASH) Annual Meeting & Exposition; December 5-8, 2020; Virtual.  
22 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.  
23 Administration USF& D. Oncologic Drugs Advisory Committee; 2024. Accessed 22 June 2024. https://www.fda.gov/advisory-committees/human-drug-advisory-committees/oncologic-drugs-advisory-committee