Summary

• 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.
• Hematologic adverse events (AEs) have been reported in the CARTITUDE-1, CARTITUDE-2 and CARTITUDE-4 studies.^1-6
• CARTITUDE-1 (MMY2001) was a phase 1b/2, open-label, single-arm, multicenter study that evaluated CARVYKTI in patients with relapsed/refractory multiple myeloma (RRMM) who had previously received a proteasome inhibitor (PI), an immunomodulatory drug, and an anti-cluster of differentiation (CD)38 antibody. The combined analysis from the phase 1b/2 portions of the CARTITUDE-1 study evaluated the efficacy and safety of CARVYKTI in 97 patients with RRMM.^1,2,6
  • At a median follow-up of 33.4 months, the most common hematologic AEs (≥20%) of any grade that had occurred were neutropenia (96%), anemia (81%), thrombocytopenia (79%), leukopenia (62%), and lymphopenia (54%). Grade 3/4 hematologic AEs included neutropenia (95%), anemia (68%), leukopenia (61%), thrombocytopenia (60%), and lymphopenia (51%).^2,6
• CARTITUDE-2 (MMY2003) is a phase 2, multicohort, open-label study evaluating CARVYKTI in patients with multiple myeloma (MM) in various clinical settings.⁷ Janssen does not recommend the use of CARVYKTI in a manner that is inconsistent with the approved labeling.
  • Cohort A is evaluating the efficacy and safety of CARVYKTI in patients who had progressive MM after 1-3 prior LOTs and were refractory to lenalidomide.^8-12
    • Initial Subgroup: evaluated the efficacy and safety of CARVYKTI manufactured with the clinical trial process in 20 patients.^8-11
      • At a median follow-up of 29.9 months, hematologic AEs of any grade were neutropenia (95%), thrombocytopenia (80%), lymphopenia (80%), anemia (75%), and leukopenia (60%). Grade 3/4 hematologic AEs included neutropenia (95%), lymphopenia (80%), leukopenia (60%), anemia (45%), and thrombocytopenia (40%).¹⁰
    • Expansion Subgroup: evaluated the efficacy and safety of CARVYKTI manufactured with a commercial process in 23 patients.¹²
      • At a median follow-up of 15.6 months, hematologic treatment-emergent adverse events (TEAEs) of any grade were neutropenia (95.7%), leukopenia (65.2%), lymphopenia (65.2%), anemia (56.5%), and thrombocytopenia (56.5%). Grade 3/4 hematologic TEAEs included neutropenia (95.7%), leukopenia (65.2%), lymphopenia (60.9%), anemia (39.1%), and thrombocytopenia (39.1%).¹²
  • Cohort B is evaluating the efficacy and safety of CARVYKTI in 19 patients who had early relapse after initial therapy with a PI and an immunomodulatory agent.^4,13,14
    • At a median follow-up of 27.9 months (range, 5.2-32.1), hematologic AEs of any grade were neutropenia (94.7%), anemia (57.9%), thrombocytopenia (57.9%), lymphopenia (47.4%), and leukopenia (31.6%). Grade 3/4 hematologic AEs included neutropenia (89.5%), anemia (47.4%), lymphopenia (47.4%), leukopenia (31.6%), and thrombocytopenia (26.3%).¹⁰
  • Cohort C is evaluating the efficacy and safety of CARVYKTI in 20 patients who had RRMM after receiving a PI, an immunomodulatory agent, an anti-CD38 antibody, and a non-cellular B-cell maturation antigen (BCMA)-directed therapy. Non-cellular BCMA-directed therapy included bispecific antibodies (BsAb) and antibody-drug conjugates (ADC).^3,15
    • At a median follow-up of 18 months, the most common hematologic AEs (≥20%) of any grade in the ADC-exposed group were neutropenia (92%), anemia (77%), thrombocytopenia (69%), leukopenia (54%) and lymphopenia (46%). The most common hematologic AEs (≥20%) of any grade in the BsAb-exposed group were thrombocytopenia (100%), neutropenia (86%), anemia (57%), leukopenia (57%) and lymphopenia (29%).³
  • Cohort D is evaluating the efficacy and safety of CARVYKTI with or without lenalidomide maintenance in 17 patients who achieved less than complete response (CR) after frontline autologous stem cell transplantation (ASCT).^16,17
    • At a median follow-up of 22.4 months, hematologic treatment emergent adverse events (TEAEs) of any grade were neutropenia (94.1%), lymphopenia (64.7%), thrombocytopenia (47.1%), leukopenia (41.2%), and anemia (29.4%). Grade 3/4 hematologic TEAEs included neutropenia (82.4%), lymphopenia (58.8%), leukopenia (35.3%), thrombocytopenia (23.5%), and anemia (5.9%).¹⁷
• 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.⁵
  • AEs were evaluated in the safety population which included all patients who received any part of study treatment (n=208 in both the CARVYKTI and standard care arm).⁵
  • At a median follow-up of 15.9 months, the most common hematologic AEs (≥20%) of any grade in the CARVYKTI arm were neutropenia (89.9%), thrombocytopenia (54.3%), anemia (54.3%) and lymphopenia (22.1%). The most common hematologic AEs (≥20%) of any grade in the standard care arm were neutropenia (85.1%), thrombocytopenia (31.2%), and anemia (26.0%).⁵

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 (MMY2001; clinicaltrials.gov identifier: NCT03548207) was a phase 1b/2, open-label, single-arm, multicenter study that evaluated the safety and efficacy of CARVYKTI in patients with RRMM who had previously received a PI, an immunomodulatory drug, and an antiCD38 antibody. The combined analysis from the phase 1b/2 portions of the CARTITUDE-1 study evaluated the safety and efficacy of CARVYKTI in 97 patients with RRMM.^1,2,6

Study Design/Methods

• The study design is presented in the Figure: CARTITUDE-1 Study Design.

Results

Treatment Disposition, Patient Demographics, and Disease/Treatment Characteristics

• 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 (progressive disease, n=2; withdrawal by subject, 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 LOTs, 88% of patients were triplerefractory, 42% of patients were penta-refractory, and 99% of patients were refractory to last LOT.^2,6

Safety - Hematologic Adverse Events

• The most common hematologic AEs that had occurred in ≥20% of patients at a median follow-up of 33.4 months (range, 1.5-45.2) are detailed in Table: CARTITUDE-1: Hematologic Adverse Events (≥20%).²
• The incidence and recovery of grade 3/4 cytopenias are noted in Table: CARTITUDE-1: Incidence and Recovery of Grade 3/4 Cytopenias.^2,20

clinical data - Cartitude-2 - Phase 2 Study

CARTITUDE-2 (MMY2003; clinicaltrials.gov identifier: 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.⁷

• Cohort A is evaluating the efficacy and safety of CARVYKTI in patients who had progressive MM after 1-3 prior LOT and were refractory to lenalidomide.^8-12
  • Initial Subgroup: evaluated the efficacy and safety of CARVYKTI manufactured with the clinical trial process in 20 patients.^8-11
  • Expansion Subgroup: evaluated the efficacy and safety of CARVYKTI manufactured with a commercial process in 23 patients.¹²
• Cohort B is evaluating the efficacy and safety of CARVYKTI in 19 patients who had early relapse after initial therapy with a PI and an immunomodulatory agent.^4,13,14
  • Early relapse was defined as progression within 12 months after autologous stem cell transplant (ASCT) or from start of anti-MM therapy for patients who have not had an ASCT.^4,13,14
• Cohort C is evaluating the efficacy and safety of CARVYKTI in 20 patients with RRMM after receiving a PI, an immunomodulatory agent, an anti-CD38 antibody, and a non-cellular BCMA-directed therapy. Non-cellular BCMA-directed therapy included BsAbs and ADCs.^3,15
• Cohort D is evaluating the efficacy and safety of CARVYKTI with or without lenalidomide maintenance in 17 patients who achieved <CR after frontline ASCT.^16,17

Study Design/Methods

• Key eligibility criteria for Cohort A: adult patients with progressive MM after 1-3 prior LOTs, including a PI and an immunomodulatory agent, who were lenalidomide refractory, had no prior exposure to BCMA-targeting agents or chimeric antigen receptor T (CAR-T) cell therapy directed at any target, and had an Eastern Cooperative Oncology Group performance status (ECOG PS) of ≤1.⁷
• Key eligibility criteria for Cohort B: adult patients who had received 1 prior LOT, including a PI and an immunomodulatory agent, had disease progression per the International Myeloma Working Group (IMWG) criteria ≤12 months after ASCT or ≤12 months from the start of anti-myeloma therapy (for patients who did not receive ASCT), had no prior exposure to BCMAtargeting agents or CAR-T cell therapy directed at any target, and had an ECOG PS of ≤1.⁷
• Key eligibility criteria for Cohort C: adult patients who were previously treated with a PI, an immunomodulatory agent, an anti-CD38 antibody, and a noncellular BCMAdirected therapy (ADC or BsAb as monotherapy or combination therapy), having a diagnosis of MM per the IMWG criteria and evidence of progressive MM ≤12 months of last LOT or ≤6 months of prior therapy and refractory to their most recent LOT, with measurable disease at baseline and an ECOG PS of ≤1.^7,15
• Key eligibility criteria for Cohort D: adult patients with a history of 4-8 cycles of initial therapy, including induction, high-dose therapy, and ASCT with or without consolidation; overall best response <CR; no prior exposure to BCMA-targeting agents and CAR-T cell therapy directed at any target; and ECOG PS ≤1.^16,17
• Dosing: patients received a single infusion of CARVYKTI at a target dose of 0.75×10⁶ viable CAR+ T cells/kg (target range, 0.5-1.0×10⁶) 5-7 days after the start of lymphodepletion/conditioning regimen (cyclophosphamide 300 mg/m² and fludarabine 30 mg/m² daily for 3 days on days -5 to -3).^{3,4,7,9,10,16,17}
• Primary endpoint: minimal residual disease (MRD) negativity at the 10^-5 sensitivity level as assessed by next-generation sequencing (clonoSEQ^®) or next-generation flow.^{3,4,7,9,10,16,17,21}
• Key secondary endpoints: ORR per IMWG criteria, duration of response, time to response, time and duration of MRD negativity, and incidence and severity of AEs.^{3,4,7,9,10,16,17}

Results

Treatment Disposition, Patient Demographics, and Disease/Treatment Characteristics

Cohort A

• Initial Subgroup: Overall, 20 patients were enrolled, lymphodepleted, and treated with CARVYKTI manufactured with the clinical trial process.^8-11
  • Patients received a median of 2 prior LOTs (range, 1-3); 95% of patients were refractory to their last LOT.⁹
• Expansion Subgroup: Overall, 24 patients were enrolled, and 23 patients were treated with CARVYKTI manufactured with a commercial process.¹²
  • Patients received a median of 3 prior LOTs (range, 1-3); 95.7% of patients were refractory to their last LOT.¹²

Cohort B

• Overall, 19 patients were lymphodepleted and treated with CARVYKTI in Cohort B of the CARTITUDE2 study.⁴
• Patients received a median of 1 prior LOT (range, 1-1); 78.9% of patients were refractory to their last LOT.⁴

Cohort C

• Overall, 24 patients were enrolled/apheresed and 20 patients (7 patients in BsAb-exposed group and 13 patients in the ADC-exposed group) were treated with CARVYKTI in Cohort C of the CARTITUDE2 study.³
• Patients received a median of 8 prior LOTs (range, 4-13); 90% of patients were anti-BCMA refractory and 95% of patients were refractory to their last LOT. In total, 30% of patients (n=6) received anti-BCMA as their last line of treatment (n=4 ADC-exposed; n=2 BsAb-exposed).^3,15

Cohort D

• Overall, 17 patients were treated with CARVYKTI in Cohort D of the CARTITUDE-2 study.¹⁷
• All 17 patients had prior ASCT and were previously exposed to PI and immunomodulatory drug; 17.6% of patients had received prior anti-CD38 monoclonal antibody therapy.¹⁷

Safety - Hematologic Adverse Events - Cohort A

• Initial Subgroup: The most common hematologic AEs occurring in patients at a median follow-up of 29.9 months (range, 3.3-35.6) are detailed in Table: CARTITUDE2 (Cohort A): Initial Subgroup Hematologic Adverse Events (≥20%).¹⁰
• Between the median follow-up of 17.1 and 29.9 months, new grade 3/4 AEs of leukopenia (n=1), lymphopenia (n=2), and thrombocytopenia (n=1) were reported.¹⁰

• Expansion Subgroup: Details regarding the incidence of treatment-emergent hematologic AEs at a median follow-up of 15.6 months (range, 1.0-29.2) in the expansion subgroup are noted in Table: CARTITUDE-2 (Cohort A) Expansion Subgroup: Hematologic TEAEs.¹²
  • All patients had grade 3 or 4 hematologic TEAEs.¹²

Safety - Hematologic Adverse Events - Cohort B

• The most common hematologic AEs occurring in patients at a median follow-up of 27.9 months (range, 5.2-32.1) are detailed in Table: CARTITUDE-2 (Cohort B): Hematologic Adverse Events (≥20%).¹⁰
• No change since the previous data cutoff of 18 months (range, 5.2-26.3).¹⁰

Safety - Hematologic Adverse Events - Cohort C

• The most common hematologic AEs occurring in ≥20% of patients at a median follow-up of 18 months (range, 0.622.7) are detailed in Table: CARTITUDE-2 (Cohort C): Hematologic Adverse Events (≥20%).³
• The proportion of patients with initial grade 3/4 cytopenias not recovered to grade ≤2 by day 60 after CARVYKTI infusion are summarized in Table: CARTITUDE-2 (Cohort C): Patients with Initial Grade 3/4 Cytopenias Not Recovered to Grade ≤2 by Day 60 After CARVYKTI Infusion.³

Safety - Hematologic Adverse Events - Cohort D

• Hematologic TEAEs at a median follow-up of 22.4 months (range, 4.7-39.3) are presented in Table: CARTITUDE2 (Cohort D): Hematologic TEAEs.¹⁷
• Prolonged cytopenias in patients with and without lenalidomide maintenance are presented in Table: CARTITUDE-2 (Cohort D): Hematologic TEAEs Between Patients with or without lenalidomide maintenance.¹⁷

clinical data - CARTITUDE-4 - PHASE 3 STUDY

CARTITUDE-4 (MMY3001; NCT04181827) is a Phase 3, randomized, open-label study evaluating the efficacy and safety of CARVYKTI versus standard care (physician's choice of DPd or PVd) in adult patients with lenalidomide-refractory MM after 1-3 prior LOT.⁵

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 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: Progression-free survival (PFS)

Safety - Hematologic Adverse Events

• At a median follow-up of 15.9 months (range, 0.1-27.3), all grade hematologic AEs occurred in 94.7% of patients in the CARVYKTI arm vs 88.9% of patients in the standard care arm.⁵ 
  • Grade 3/4 hematologic AEs occurred in 94.2% of patients in the CARVYKTI arm vs 86.1% of patients in the standard care arm.
• In the CARVYKTI arm, the most common all grade hematologic AEs occurring in ≥20% of patients were neutropenia (89.9%), thrombocytopenia (54.3%), anemia (54.3%), and lymphopenia (22.1%).⁵
  • The most common grade 3/4 hematologic AEs occurring in ≥20% were neutropenia (89.9%), thrombocytopenia (41.3%), anemia (35.6%), and lymphopenia (20.7%).
• In the standard care arm, the most common all grade hematologic AEs occurring in ≥20% of patients were neutropenia (85.1%), thrombocytopenia (31.2%), anemia (26%), and lymphopenia (13.9%).⁵ 
  • The most common grade 3/4 hematologic AEs occurring in ≥20% were neutropenia (82.2%), thrombocytopenia (18.8%), anemia (14.4%), and lymphopenia (12.0%).
• Of the patients who received CARVYKTI as study treatment (n=176), the incidence of grade 3/4 cytopenias included: lymphopenia, 100%; neutropenia, 94.9%; thrombocytopenia, 40.9%; and anemia, 29.5%.²²
  • The incidence of prolonged (>30 days) grade 3/4 cytopenias included: lymphopenia, 29%; neutropenia, 26.1%; thrombocytopenia, 26.1%; and anemia, 1.7%.
  • The incidence of prolonged (>60 days) grade 3/4 cytopenias included: lymphopenia, 10.2%; neutropenia, 10.2%; thrombocytopenia, 10.8%; and anemia, 1.1%.        

LITERATURE SEARCH

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File databases (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 03 July 2025.