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.
• Cytokine release syndrome (CRS) has been reported as an adverse event (AE) in the CARTITUDE-1, CARTITUDE-2 and CARTITUDE-4 studies.^1-6
• 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).^1,2,7,8
  • At a median follow-up of 61.3 months, no new CRS events were reported.^8,9
  • At a median follow-up of 33.4 months, CRS of any grade had occurred in 95% of patients, with grade 3/4 CRS occurring in 4.1% of patients and grade 5 CRS occurring in 1 patient. The median duration of CRS was 4 days (interquartile range [IQR] 3-6). The median time to onset of CRS was 7 days (IQR 5-8 days), with 89% of patients experiencing CRS onset at day 4 or later. CRS resolved within 14 days of onset in 99% of patients.^1,7 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.^2,7
• 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.¹⁰
  • Cohort A evaluates patients with RRMM who received 1-3 prior LOTs and are refractory to lenalidomide.^11-15
    • Initial Subgroup: evaluated the efficacy and safety of CARVYKTI manufactured with the clinical trial process in 20 patients.^11-14
      • At a median follow-up of 29.9 months, CRS of any grade occurred in 95% of patients (n=19), with grade 3/4 CRS occurring in 10% of patients (n=2). The median time to CRS onset was 7 days, with a median CRS duration of 3 days. CRS resolved in all patients.¹³
    • Expansion Subgroup: evaluated the efficacy and safety of CARVYKTI manufactured with a commercial process in 23 patients.¹⁵
      • At a median follow-up of 15.6 months, CRS of any grade occurred in 100% of patients (n=23); no grade 3/4 CRS occurred. The median time to CRS onset was 8 days and recovery was 4 days.¹⁵
  • Cohort B evaluates patients with early relapse (≤12 months after frontline therapy or ≤12 months after autologous stem cell transplant [ASCT]).^4,13,16,17
    • At a median follow-up of 27.9 months, CRS of any grade occurred in 84.2% of patients (n=16), with grade 3/4 CRS occurring in 5.3% of patients (n=1). The median time to CRS onset was 8 days, with a median CRS duration of 4 days. CRS resolved in all patients.¹³
  • 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).^3,18
    • At a median follow-up of 18 months, CRS of any grade occurred in 60% of patients (n=12) overall with no grade 3/4 CRS reported. The median time to CRS onset was 7.5 days (range, 2-10) with a median duration of 5.5 days (range, 3-10). CRS resolved in all patients.³
  • Cohort D evaluates patients with RRMM who achieved less than a complete response (<CR) after frontline ASCT, with or without lenalidomide maintenance.^5,19,20
    • At a median follow-up of 40.2 months, no new CRS events were reported.²⁰
    • At a median follow-up of 22.4 months, CRS of any grade occurred in 82.4% of patients (n=14) overall, with no grade 3/4 CRS reported. The median time to CRS onset was 8 days with a median duration of 2.5 days.¹⁹
• 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.^6,21,22
  • At a median follow-up of 33.6 months (IQR, 20.3-35.0), grade 1/2 CRS occurred in 63.5% (n=132) of patients in CARVYKTI arm and 0.5% (n=1) of patients in standard-care arm in safety population. No grade 4/5 CRS occurred in both arms.^22,23 
  • Chimeric antigen receptor (CAR)-T specific AEs were evaluated in the as-treated population which included patients who received CARVYKTI as study treatment (n=176).²¹
    • At a median follow-up of 33.6 months (IQR, 20.3-35.0), CRS of any grade occurred in 76.1% (n=134) of patients that received CARVYKTI as study treatment with grade 3/4 CRS occurring in 1.1% of patients (n=2) in as-treated population.²³
    • At a median follow-up of 16.0 months, CRS of any grade occurred in 76.1% (n=134) of patients that received CARVYKTI as study treatment with grade 3/4 CRS occurring in 1.1% of patients (n=2). The median time to onset of CRS was 8 days with a median duration of 3 days. CRS resolved in all patients.²¹
  • 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.²⁴
    • At a median follow-up of 15.9 months, among patients who received 1 prior LOT (N=68), CRS of any grade occurred in 64.7% of patients (n=44), with grade 3/4 CRS occurring in 1.5% of patients (n=1). Among patients who received 1 prior LOT and had functionally high-risk MM (N=40), CRS of any grade occurred in 62.5% of patients (n=25), with no grade 3/4 CRS reported.²⁴

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.^1,2,7

Study Design/Methods

• Treatment arm: CARVYKTI (single arm)
• Key eligibility criteria:
  • Progressive MM per International Myeloma Working Group 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, overall response rate
• Per protocol, hospital stay was mandated for least 14 days post-infusion for the first
  6 patients within Phase 1b of the CARTITUDE-1 study. Subsequently, per Safety Evaluation Team recommendation, hospital stay guidance was decreased to at least
  10 days post-infusion.²⁵
• Body temperature was monitored twice daily for 28 days post CARVYKTI infusion.²⁶
• All patients were monitored and hospitalized for evaluation at the first sign of CRS.²⁶
• Cytokine profiling was conducted by collecting serum samples prior to lymphodepletion, prior to CARVYKTI infusion, 2 hours post-infusion on day 1, and on additional days (days 2, 3, 7, 10, 14, 21, 28, 42, 56, and 78) until day 100. Samples were also collected if CRS was reported or suspected in a patient.²⁶

Results

Safety - Adverse Events - CRS

• At a median follow-up of 61.3 months, no new CRS events were reported.^8,9
• The incidence, timing/duration, and management of CRS are detailed in Table: CARTITUDE-1: CRS.
  • At a median follow-up of 33.4 months (range, 1.5-45.2), CRS had occurred in 95% of patients (92/97). Overall, 51% of patients (n=49) had grade 1 CRS and 39% of patients (n=38) had grade 2 CRS. Five CRS events were grade ≥3 (Grade 3/4, n=4; Grade 5, n=1).^1,7
  • Median time to CRS onset was 7 days (IQR 5-8 days), with 89% of patients experiencing CRS onset at day 4 or later, and 74% of patients experiencing CRS onset at day 6 or later.^1,27
  • Median duration of CRS was 4 days (IQR 3-6 days) and resolved in 91 (99%) patients within 14 days of onset.^1,27
• One death due to CRS/hemophagocytic lymphohistiocytosis occurred on day 99 post CARVYKTI infusion.¹
• No new events of CRS (no changes in the incidence, time to onset, or duration) occurred since the median 12.4 month follow-up.²
• Anakinra was administered in patients for whom tocilizumab did not effectively manage CRS.²⁸ Use of anakinra per study patient with CRS event is presented in Table: CARTITUDE-1: Use of Anakinra Per Study Patient with CRS Event.
  • A total of 18 patients received anakinra for CRS, typically within the first 48 hours of CRS onset (range, 0-6 days).²⁸
  • Subcutaneous injection of anakinra 100-200 mg was administered every 8-12 hours over a median of 2.5 days (range, 1-15 days).²⁸
  • CRS resolved after a median of 5 days (range, 2-10 days) in patients who received anakinra and tocilizumab, with (n=14) or without (n=4) steroids.²⁸
• CARVYKTI CAR+ T cells revealed maximum peripheral expansion at a median of 12.7 days (range 8.7-54.6 days).¹
• Interleukin (IL)-6, IL-10, and interferon (IFN)-gamma levels peaked at days 7-14 postCARVYKTI infusion.²⁶
  • CRS severity and supportive measures were associated with peak levels of IL-6, IL-10, and IFN-gamma. The results were similar for other cytokines (IL-2, IL-8, soluble IL-2Ra, and TNF-α).²⁶
• No association was observed between the severity of CRS and baseline or peak levels of C-reactive protein (CRP) or ferritin.²⁶
  • CRP and ferritin trends follow cytokine levels and can be useful for monitoring CRS.²⁶
• Incidence of CRS in key subgroups in CARTITUDE-1 (≥65 years of age, Black/African American, 3 and ≥4 prior LOT, triple-class refractory, penta-drug refractory, cytogenetic risk status, International Staging System stage III disease at baseline, bone marrow plasma cell percentage at baseline (≤30%, >30 to <60%, and ≥60%), tumor BCMA expression at baseline (<median, ≥median), and presence of soft-tissue plasmacytomas (bone-based and extramedullary disease) was consistent with the overall population.^2,29

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.¹⁰

• Cohort A evaluates patients with RRMM who received 1-3 prior LOT and are refractory to lenalidomide.^11-15
  • Initial Subgroup: evaluated the efficacy and safety of CARVYKTI manufactured with the clinical trial process in 20 patients.^11-14
  • Expansion Subgroup: evaluated the efficacy and safety of CARVYKTI manufactured with a commercial process in 23 patients.¹⁵
• Cohort B evaluates patients with early relapse (≤12 months after frontline therapy or ≤12 months after ASCT).^4,13,16,17
  • Early relapse was defined as progression within 12 months after ASCT or from start of anti-MM therapy for patients who have not had an ASCT.^4,13,16,17
• Cohort C evaluates patients with RRMM with prior exposure to a PI, immunomodulatory drug, and an anti-CD38 mAb, and a BCMA BsAb or ADC.^3,18
• Cohort D evaluates patients with RRMM who achieved <CR after frontline ASCT, with or without lenalidomide maintenance.^5,19

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.^10,13
  • 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.¹⁰
  • Cohort C: Previously treated with a PI, an immunomodulatory drug, an anti-CD38 mAb, and BCMA BsAb or ADC.^10,18
  • 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.^5,19
• Primary endpoint: minimal residual disease negativity at the 10^-5 sensitivity level as assessed by next-generation sequencing or next-generation flow.^{3-5,10,12,13,19,31}

Results

Safety - Adverse Events - CRS - Cohort A

• Initial Subgroup: The incidence and timing/duration of CRS are summarized in Table: CARTITUDE-2 (Cohort A) Initial Subgroup: CRS.¹³
  • At a median follow-up of 29.9 months (range, 3.3-35.6), any grade CRS occurred in 95% (n=19) of patients. Grade 3/4 CRS occurred in 10% (n=2) of patients.The median time to onset of CRS was 7 days, with a median CRS duration of 3 days. At the time of data cutoff, CRS had resolved in all 19 patients.¹³
• Expansion Subgroup: At a median follow-up of 15.6 months (range, 1.0-29.2), CRS of any grade occurred in 100% of patients (n=23); no grade 3/4 CRS occurred.The median time to CRS onset was 8 days and recovery was 4 days.¹⁵

Safety - Adverse Events - CRS - Cohort B

• The incidence and timing/duration of CRS are detailed in Table: CARTITUDE-2 (Cohort B): CRS.¹³
• At a median follow-up of 27.9 months (range, 5.2-32.1), any grade CRS occurred in 84.2% (n=16) of patients. Grade 3/4 CRS occurred in 5.3% (n=1) of patients.¹³
• At the time of data cutoff, CRS had resolved in all 16 patients.¹³

Safety - Adverse Events - CRS - Cohort C

• The incidence, timing/duration, and management of CRS are detailed in Table: CARTITUDE-2 (Cohort C): CRS.³
• At a median follow-up of 18 months (range, 0.622.7), CRS occurred in 60% of patients (n=12) overall, with 6 patients in each of the ADC-exposed and BsAb-exposed groups.^3,18
• The median time to onset of CRS was 7.5 days (range, 2-10) with a median duration of 5.5 days (range, 3-10).³
• All patients who experienced CRS received ≥1 treatment (tocilizumab n=9; anakinra n=3, corticosteroids n=6).³
• CRS resolved in all patients at the time of data cutoff.^3,18

Safety - Adverse Events - CRS - Cohort D

• At a median follow-up of 40.2 months (range, 4.7-55.9), no new CRS events were reported.²⁰
• At a median follow-up of 22.4 months (range, 4.7-39.3), CRS occurred in 82.4% of patients overall (n=14). The incidence, timing/duration of CRS is detailed in Table: CARTITUDE-2 (Cohort D): CRS.¹⁹

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.^6,21,22

Study Design/Methods

• Treatment arms: Randomized 1:1 to receive either CARVYKTI or standard care (DPd or PVd)
• 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

Results

Safety - Adverse Events - CRS

• At a median follow-up of 33.6 months (IQR, 20.3-35.0) treatment-emergent AEs and treatment-related AEs were evaluated in CARVYKTI arm and standard-care arm in the safety population (n=208 for both arms).^22,23
  • Treatment-emergent CRS events:
    • Grade 1/2 CRS occurred in 63.5% of patients (n=132) in the CARVYKTI arm and 0.5% of patients (n=1) in the standard-care arm.
    • Grade 3 CRS occurred in 1.0% of patients (n=2) in the CARVYKTI arm.
    • Grade 4 or grade 5 CRS events did not occur in CARVYKTI or standard-care arms.
    • CRS was reported as a serious AE (≥1% of patients in any arm) in 3.4% of patients (n=7) in the CARVYKTI arm and 0.5% of patients (n=1) in the standard-care arm.
  • Treatment-related CRS events: CRS was reported as a serious AE (≥1% of patients in any arm) in 3.4% of patients (n=7) in the CARVYKTI arm and 0.5% of patients (n=1) in the standard-care arm.
• CAR-T specific AEs were evaluated in patients treated with CARVYKTI as study treatment (as-treated population; n=176).^21,22,32
  • At a median follow-up of 33.6 months (IQR, 20.3-35.0), any-grade CRS occurred in 76.1% of patients (n=134) in the as-treated population receiving CARVYKTI.²³
    • Grade 3 or 4 CRS was reported in 1.1% of patients (n=2).
  • At a median follow-up of 16.0 months (range, 3.8-27.3), CRS occurred in 76.1% (n=134) of patients in the as-treated population receiving CARVYKTI.^21,32
    • Most of the CRS events were grade 1 or grade 2 (52.8% vs 22.2%, respectively) with grade 3 events occurring in 1.1% of patients. CRS resolved in all patients.
    • The median time to onset of CRS was 8 days (range, 1-23), with a median CRS duration of 3 days (range, 1-17).
    • Supportive treatments (n=131) included: tocilizumab (n=71), oxygen therapy (n=17), corticosteroids (n=8), and vasopressors (n=2).

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.

Results

Treatment Disposition, Patient Demographics, and Disease/Treatment Characteristics

• A total of 136 patients received 1 prior LOT in the CARTITUDE-4 study.²⁴
  • In the CARVYKTI arm, 68 patients underwent apheresis/bridging therapy; 40 patients had functionally high-risk MM. Of the 68 patients, 60 patients received CARVYKTI as study treatment; 35 patients had functionally high-risk MM.²⁴
  • A total of 68 patients received standard care; 39 of these patients had functionally high-risk MM.²⁴
  • Functionally high-risk MM defined as PD ≤18 months after receiving ASCT or the start of initial frontline therapy in patients with no ASCT.²⁴

Safety - Adverse Events - CRS

• The incidence of CRS at a median follow-up of 15.9 months (range, 0.1-28.3) is detailed in Table: CARTITUDE-4: CRS in CARVYKTI Patients With 1 Prior LOT and Those With 1 Prior LOT and Functionally High-Risk MM.

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 02 March 2026.