Summary

• 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 agent, and an anti-cluster of differentiation 38 (anti-CD38) 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.^1-3
• After a median follow-up of 27.7 months, the overall response rate (ORR) was 97.9% with a stringent complete response (sCR) rate of 82.5%. Median progression free survival (PFS) and overall survival (OS) were not reached, and the 27-month PFS rate and OS rate in the overall population were 54.9% and 70.4%, respectively.^1,4
• The efficacy and safety of CARVYKTI were evaluated in key subgroups of patients in the CARTITUDE-1 study after a median follow-up of 21.7 months and 27.7 months.^1,5
  • Data was presented from the following subgroups: ≥65 years of age, Black/African American, 3 and ≥4 prior lines of therapy (LOT), triple-class refractory, penta-drug refractory, cytogenetic risk status, International Staging System (ISS) stage III disease at baseline, bone marrow plasma cell percentage at baseline (≤30%, >30 to <60%, and ≥60%), tumor B-cell maturation antigen (BCMA) expression at baseline (<median, ≥median), and presence of soft-tissue plasmacytomas (bone-based and extramedullary disease [EMD]).^1,5
  • Responses were observed in most patients in high-risk subgroups (ORR range, 95.1100%), including patients with 3 prior LOT, high-risk cytogenetic profile, ISS stage III multiple myeloma (MM) at baseline, baseline bone marrow cells ≥60%, and baseline plasmacytomas.^1,5 Efficacy outcomes in key subgroups of patients at a median follow-up of 27.7 months are presented in Table: CARTITUDE-1: Efficacy Outcomes in Key Subgroups at a Median Follow-up of 27.7 Months.
  • MRD negativity rates at the 10^-5 sensitivity were 80-100% in evaluable patients across all subgroups.¹
  • Duration of response (DOR), PFS and/or OS were shorter in patient-subgroups with high-risk cytogenetics, ISS stage III disease, high tumor burden and presence of plasmacytomas.¹
    • A shorter DOR was observed in patients with 30-60% bone marrow plasma cells.¹
    • A lower OS was observed in Black/African American patients.¹
  • The incidence of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and other chimeric antigen receptor-T (CAR-T) cell neurotoxicities (events not reported as ICANS) in the subgroups was consistent with the overall population.⁵

Clinical Data

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 anti-CD38 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.^1-3

The efficacy and safety of CARVYKTI in key subgroups of patients in the CARTITUDE-1 study were evaluated after a median follow-up of 21.7 months and 27.7 Months.^1,5

Study Design/Methods

• The study design is presented in the Figure: CARTITUDE-1 Study Design
• An analysis was conducted in the following subgroups: age ≥65 years, Black/African American, 3 and ≥4 prior LOT, triple-class refractory, penta-drug refractory, cytogenetic risk status (including ≥1 chromosomal abnormality: del17p, t(4;14), and/or t(14;16)), ISS 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 EMD).^1,5

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.¹ Baseline characteristics of key subgroups are presented in Table: CARTITUDE-1: Baseline Characteristics of Key Subgroups.
• Baseline cytogenic data was available in 94% of patients (n=91); 24% of patients (n=23) had a highrisk cytogenetic profile based on the presence of ≥1 chromosomal abnormality including del17p (20%), t(4;14) (3%), and/or t(14;16) (2%).^1,5
• A total of 96 patients had evaluable bone marrow biopsy and/or aspirate samples; 22% of patients (n=21) had high disease burden (≥60% plasma cells).^1,5
• At baseline, plasmacytomas were detected in 20% of patients (n=19); 13% (n=13) were EMD and 6% (n=6) were bone-based plasmacytomas.^1,5

Efficacy

• At data cut-off, the safety and efficacy of CARVYKTI in key subgroups of patients were evaluated at a median follow-up of 21.7 months (range, 1.5-33.9) and 27.7 months.^1,5
• Responses were observed in most patients in high-risk subgroups (ORR range, 95.1100%) including patients with 3 prior LOT (100%), high-risk cytogenetics (100%), high tumor burden (≥60% bone marrow plasma cells; 95.2%), and baseline plasmacytomas (100%).^1,5
• MRD negativity rates at the 10^-5 sensitivity was 80-100% in evaluable patients across all subgroups.^1,5
• DOR, PFS and/or OS were shorter in subgroups with high-risk cytogenetics, ISS stage III disease, high tumor burden and presence of plasmacytomas.^1,5
  • A shorter DOR was observed in patients with 30-60% bone marrow plasma cells.¹
  • A lower OS was observed in Black/African American patients.¹

Safety

• The incidence of CRS, ICANS, and other CAR-T cell neurotoxicities (events not reported as ICANS) in subgroups was consistent with the overall population.⁵

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 April 2024.