CARVYKTI - Adverse Event - Mortality

SUMMARY

• Johnson & Johnson does not recommend the use of CARVYKTI in a manner that is inconsistent with the approved labeling.
• Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
• 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 (LOTs) including a proteasome inhibitor (PI), an immunomodulatory drug, and an anti-cluster of differentiation (CD) 38 monoclonal antibody (mAb).^1-4
  • Jagannath et al (2025)⁴ reported 47 deaths after CARVYKTI infusion, at a median follow-up of 61.3 months (N=97): 17 occurred without progressive disease.
  • Lin et al (2023)³ reported 35 deaths after CARVYKTI infusion, at a median follow-up of 29.9 months (N=97): 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.⁵
  • Cohort A evaluates patients with RRMM who received 1-3 prior LOTs and are refractory to lenalidomide.^6-9
    • Hillengass et al (2023)⁸ reported 5 deaths after CARVYKTI infusion, at a median follow-up of 29.9 months. 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).
    • Cohen et al (2024)¹⁰ reported 1 treatment-related death (sepsis, diagnosed on day 30) after CARVYKTI infusion, at a median follow-up of 15.6 months.
  • Cohort B evaluates patients with early relapse (≤12 months after frontline therapy or ≤12 months after autologous stem cell transplant [ASCT]).^11-13
    • Hillengass et al (2023)⁸ reported 4 deaths after CARVYKTI infusion, at a median follow-up of 27.9 months. 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).^14,15
    • Cohen et al (2022)¹⁵ reported 12 deaths after CARVYKTI infusion, at a median follow-up of 18 months. 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.^5,16,17
    • Cohen et al (2025)¹⁷ reported no deaths due to treatment-emergent adverse events (TEAEs), at a median follow-up of 40.2 months.
    • Arnulf et al (2024)¹⁶ reported no deaths due to TEAEs, at a median follow-up of 22.4 months.
• 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 LOTs, including a PI and an immunomodulatory drug, and are refractory to lenalidomide.^18,19 
  • Costa et al (2024)²⁰ reported 11 deaths in each of the CARVYKTI and standard care arms among patients who received 1 prior LOT, at a median follow-up of 15.9 months. Of these patients, 7 patients in the CARVYKTI arm and 9 patients in the standard care arm had functionally high-risk MM.
  • Einsele et al (2026)¹⁹ reported 50 deaths (24%) in the CARVYKTI arm and 82 deaths (39%) in the standard care arm, at a median follow‑up of 33.6 months in the safety population (n=208 per group).
  • San-Miguel et al (2023)¹⁸ reported 39 deaths (18.8%) in the CARVYKTI arm and 46 deaths (22.1%) in the standard care arm, at a median follow‑up of 15.9 months in the safety population (n=208 per group).
• The Food and Drug Administration (FDA) Oncologic Drugs Advisory Committee (ODAC) reviewed the overall survival (OS) data and the risk and benefit of CARVYKTI from the CARTITUDE-4 clinical trial in March 2024.²¹
  • With a data cut-off date of December 13, 2023, information on patient deaths within the first 6 months of CARVYKTI infusion can be found in Table: CARTITUDE-4: Total Deaths and Causes of Deaths at 0-≤3 and >3-≤6 Months (ITT Analysis Set).

PRODUCT LABELING

• CARVYKTI (ciltacabtagene autoleucel) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/CARVYKTI-pi.pdf.
• DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/DARZALEX+Faspro-pi.pdf

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

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

• Treatment arm: CARVYKTI (single arm)
• Key eligibility criteria:^3,22,23
  • 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 chimeric antigen receptor T-cell (CAR-T) or BCMA targeting therapy
• Primary endpoints: Recommended phase 2 dose, overall response rate.^3,22,23

Jagannath et al (2025)⁴ reported the incidence and causes of death at a median follow-up of 61.3 months.

• Among the 47 total deaths in CARVYKTI-treated patients (N=97), 17 occurred without progressive disease as follows²⁴: 
  • Seven deaths within the first 12 months (infections: n=4; hemophagocytic lymphohistiocytosis, respiratory failure, and neurotoxicity: n=1 each)
  • Two deaths between 12 and 24 months (acute myeloid leukemia [AML] and ascites: n=1 each)
  • Six deaths between 24 and 36 months (infections: n=3; myelodysplastic syndrome, acute myocardial infarction, and respiratory failure: n=1 each)
  • Two deaths between 36 and 60 months (infection and AML: n=1 each).

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

clinical data - CARTITUDE-2 - PHASE 2 STUDY

CARTITUDE-2 (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.⁵

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.⁵
  • 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.⁵
  • Cohort C: Previously treated with a PI, an immunomodulatory drug, an anti-CD38 mAb, and BCMA BsAb or ADC.^5,14
  • 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.^8,16
• Primary endpoints: Minimal residual disease negativity at the 10^-5 sensitivity level defined by IMWG criteria (assessed by next-generation sequencing or next-generation flow).^6,13,15

Cohort A

Hillengass et al (2023) reported 5 deaths after CARVYKTI infusion, at a median follow-up of 29.9 months (range, 3.3-35.6). 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).⁸

Cohen et al (2024)¹⁰ reported 1 treatment-related death after CARVYKTI infusion (sepsis, diagnosed on day 30), at a median follow-up of 15.6 months (range, 1.0-29.2).

Cohort B

Hillengass et al (2023)⁸ reported 4 deaths after CARVYKTI infusion, at a median follow-up of 27.9 months (range, 5.2-32.1). 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)¹⁵ reported 12 deaths after CARVYKTI infusion, at a median follow-up of 18 months (range, 0.622.7). 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).

Cohort D

Cohen et al (2025)¹⁷ reported no deaths due to TEAEs, at a median follow-up of 40.2 months (range, 4.7-55.9).

Arnulf et al (2024)¹⁶ reported no deaths due to TEAEs, at a median follow-up of 22.4 months (range, 4.7-39.3).

CLINICAL DATA - CARTITUDE-4 - PHASE 3 STUDY

CARTITUDE-4 (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 LOTs.^18,19

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 LOTs including a PI and an immunomodulatory drug
  • Refractory to lenalidomide
  • No prior exposure to CAR-T or BCMA targeting therapy
• Primary endpoint: Progression-free survival

Costa et al (2024)²⁰ reported 11 deaths in each of the CARVYKTI and standard care arms among patients who received 1 prior LOT, at a median follow-up of 15.9 months (range, 0.1-27.3). 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.²⁰

Einsele et al (2026)¹⁹ published prespecified second interim analysis of OS and updated efficacy and safety outcomes at a median follow up of 33.6 months (interquartile range, 20.3-35.0). At the data cut-off date of May 1, 2024, 117 patients in the CARVYKTI arm were in the post-treatment phase and 43 patients were undergoing standard-care therapy.

• In the safety population, 50 (24.0%) CARVYKTI patients and 82 (39.4%) standard care patients had died. See Table: CARTITUDE-4: Causes of Deaths (Safety Population).
• Deaths since CARVYKTI infusion in the as-treated population across defined time intervals are detailed in Table: CARTITUDE-4: Deaths Within First 3 Years After CARVYKTI Infusion (As-treated Population).
• Deaths in the intention-to-treat population at different time intervals since randomization are detailed in Table: CARTITUDE 4: Deaths Since Randomization in Treatment Groups (ITT Population).
• In the CARVYKTI arm, 33 (16%) patients had died within the 1^st year of randomization.¹⁹
  • Of the 33 patients, 11 (5%) did not receive CARVYKTI; 9 (4%) progressed during bridging therapy and received CARVYKTI as the next LOT; and 13 (6%) received CARVYKTI as study treatment, nearly half of whom died due to COVID19 pneumonia.
  • Among the 176 patients who received CARVYKTI as study treatment, non‑relapse deaths were primarily due to infections during the 1^st year.
• In the safety population, grade 5 infections were reported in 16 (8%) CARVYKTI patients and 19 (9%) standard‑care patients.¹⁹
  • During the 1^st year from the start of treatment, 13 (6%) CARVYKTI patients and 8 (4%) standard‑care patients had died.
  • During the 2^nd year from the start of treatment, 2 (1%) CARVYKTI patients and 8 (4%) standard‑care patients had died.

CARTITUDE-4: Causes of Deaths (Safety Population)^19,25,a

San-Miguel et al (2023)¹⁸ 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.^18,26
  • 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.^18,26
  • 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 FDA 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.²⁷
• In March 2024, the ODAC reviewed the OS data and the risk and benefit of CARVYKTI from the CARTITUDE-4 clinical trial.²¹
  • With a data cut-off date of December 13, 2023, information on patient deaths within the first 6 months of CARVYKTI infusion can be found in Table: CARTITUDE-4: Total Deaths and Causes of Deaths at 0-≤3 and >3-≤6 Months (ITT Analysis Set).²¹
  • For more information, reference the following: March 15, 2024: Meeting of the Oncologic Drugs Advisory Committee Meeting Announcement.²¹

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 27 February 2026.