Summary

• Janssen does not recommend the use of CARVYKTI in a manner that is inconsistent with the approved labeling.
• CARTITUDE-2 (MMY2003) is a phase 2, multicohort, open-label study evaluating CARVYKTI in patients with multiple myeloma (MM) in various clinical settings. Cohort D is evaluating the efficacy and safety of CARVYKTI in patients who achieved less than complete response (CR) after frontline autologous stem cell transplantation (ASCT).^1-3
• Efficacy outcomes are presented in Table: CARTITUDE-2 Cohort D: Efficacy - Response.³
  • At a median follow-up of 22.4 months (range, 4.7-39.3), a total of 15 patients had minimal residual disease (MRD)-evaluable samples at the 10^-5 threshold; 12 patients (80.0%) were MRD negative (primary endpoint).³
• The most common 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%).³
• Cytokine release syndrome (CRS) of any grade occurred in 14 patients (82.4%) 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.³
• Immune effector cell-associated neurotoxicity syndrome (ICANS) of any grade occurred in 1 patient (5.9%) overall, with no grade 3/4 ICANS reported. The median time to ICANS onset was 7 days with a median duration of 1 day. ICANS resolved in the 1 patient.³
• No cases of movement and neurocognitive treatment-emergent adverse events (MNTs)/parkinsonism were reported for patients in Cohort D.³
• One case of second primary malignancy (grade 3 myelodysplastic syndrome; not treatment related) was reported with onset on day 353.³
• No deaths due to TEAEs were reported at the time of the data cutoff.³

CLINICAL DATA

CARTITUDE-2 (MMY2003; clinicaltrials.gov identifier: NCT04133636) is a phase 2, multicohort, open-label study evaluating CARVYKTI in patients with MM in various clinical settings.^1-3

Cohort D of the CARTITUDE-2 study is evaluating the efficacy and safety of CARVYKTI with or without lenalidomide maintenance in patients who achieved <CR after frontline ASCT.^1-3

Study Design/Methods

• The study design is presented in the Figure: CARTITUDE-2 (Cohort D) Study Design.

Results

Patient Demographics and Disease/Treatment Characteristics

• Overall, 17 patients were treated with CARVYKTI in Cohort D of the CARTITUDE-2 study. Patient details are presented in Table: CARTITUDE-2 (Cohort D): Demographics and Disease Characteristics.³
• Per protocol, the first 5 patients did not receive lenalidomide maintenance after CARVYKTI; 12 patients initiated continuous lenalidomide maintenance after CARVYKTI at a dose of 10mg daily upon adequate hematologic recovery.³
  • A summary of lenalidomide maintenance after CARVYKTI treatment in the 12 patients who initiated continuous lenalidomide maintenance after CARVYKTI is presented in Table: CARTITUDE-2 (Cohort D): Summary of Lenalidomide Maintenance After CARVYKTI.³

Efficacy

• Efficacy outcomes after a median follow-up of 22.4 months (range, 4.7-39.3) are presented in Table: CARTITUDE-2 (Cohort D): Efficacy - Response.³
  • One patient was lost to follow-up, and 1 patient was not evaluable for disease response.³

Safety

• Select TEAEs at a median follow-up of 22.4 months are presented in Table: CARTITUDE2 (Cohort D): Select TEAEs.³
• Prolonged cytopenias and grade 3/4 infections in patients with and without lenalidomide maintenance are presented in Table: CARTITUDE-2 (Cohort D): TEAEs Between Patients with or without lenalidomide maintenance .³
• Second primary malignancy was reported in 1 patient (grade 3 myelodysplastic syndrome with an onset on day 353; not treatment related per investigator assessment).³
• At the time of the data cutoff (September 5, 2023), no deaths due to TEAEs were reported.³

Cytokine Release Syndrome

• 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.³

Neurotoxicity

• The incidence of neurotoxicity is detailed in Table: CARTITUDE-2 (Cohort D): Neurotoxicity.³
  • ICANS was reported in 1 patient, which resolved. The median time to onset of ICANS was 7 days with a median duration of 1 day.³
  • Other neurotoxicities of any grade occurred in 6 patients. A grade 3/4 event occurred in 1 patient. The median time to onset of other neurotoxicities was 21 days with a median duration of 111 days.³
    • Three patients had cranial nerve VII disorders and associated symptoms including Bell’s palsy, facial nerve palsy, facial nerve disorder, and dysarthria (grade 1 and ongoing in 1 patient, 1 patient with facial nerve palsy not resolved by data cutoff).³
    • One patient had diplopia and oral hypoesthesia, which resolved; diplopia reached a maximum of grade 3 and recovered after a duration of 43 days.³
    • One patient had grade 1 paresthesia, which was ongoing at data cutoff.³
    • One patient had peripheral motor neuropathy, dysarthria, and dysphagia, which resolved.³
  • No cases of MNTs/parkinsonism were observed.³

Pharmacokinetics

• CAR-T cell expansion profile is presented in Table: CARTITUDE-2 (Cohort D): CAR-T Cell Expansion Profile.³
• Both chimeric antigen receptor (CAR)+ cluster of differentiation (CD)4 and CAR+ CD8 T cells expanded after infusion.³
  • CAR+ CD8 T cells expanded more than CAR+ CD4 T cells in blood. See Figure: CARTITUDE-2 (Cohort D): CAR+ CD4 and CAR+ CD8 T-cell Levels.³
• CAR+ CD4:CD8 T-cell ratios were lower in blood at ~T_max than in drug product (P<0.005). See Figure: CARTITUDE-2 (Cohort D): CAR+ CD4:CD8 T-cell Ratio.³

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 11 June 2024.