The Janssen Pharmaceutical Companies of Johnson & Johnson announced that results from the Phase 3 CARTITUDE-4 study showed CARVYKTI® (ciltacabtagene autoleucel; cilta-cel) reduced the risk of disease progression or death by 74% compared to two standard of care treatment (SOC) regimens, pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd), in adults with relapsed and lenalidomide-refractory multiple myeloma who received one to three prior lines of therapy. These data were featured in the press program and as an oral presentation in a special session at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract #LBA106) and were simultaneously published in The New England Journal of Medicine. The results will also be presented at the European Hematology Association (EHA) Hybrid Congress (Abstract #S100) as part of the plenary session on Saturday, June 10, 2023.

The CARTITUDE-4 study is the first randomized study investigating the efficacy of a cell therapy as early as after first relapse in multiple myeloma. The Phase 3 CARTITUDE-4 study included patients (n=419) who received one to three prior lines of therapy, including a proteasome inhibitor (PI) and immunomodulatory agent (IMiD), and were lenalidomide-refractory. Patients were randomized [cilta-cel, n=208; SOC, n=211], and those in the CARVYKTI® arm then underwent apheresis.

In the CARVYKTI® arm, 50% of patients were refractory to treatment with a PI and 23% were refractory to treatment with anti-CD38 therapies; in the SOC group, 46% and 21% of patients were refractory to PI and anti-CD38 therapies, respectively. Thirty-three% of patients in the CARVYKTI® group received one prior line of treatment, compared to 32% of patients in the SOC group. At a median follow-up of 16 months, a 74% (Hazard Ratio [HR]=0.26; 95% Confidence Interval [CI], 0.8–0.38; p value p<0.0001) reduction in the risk of disease progression or death was observed in patients randomized to the CARVYKTI® arm compared to SOC treatments.

Among patients in the CARVYKTI® arm, median progression-free survival (PFS) was not reached and in the SOC arm, median PFS was 11.8 months. Progression-free survival (PFS) at 12 months for patients in the CARVYKTI® arm and SOC arm was 76% (95% CI, 69-81) and 49% (95% CI, 42-55), respectively. At the data cut-off, patients randomized to the CARVYKTI® arm achieved an 85% overall response rate (ORR) and 73% achieved a complete response (CR) or better.

Among patients in the SOC arm, the ORR was 67% and CR or better was 22%. In 144 patients in the CARVYKTI® arm and 101 patients in the SOC arm evaluable for minimal residual disease (MRD) status, 88% of patients randomized to the CARVYKTI® arm and 33% of patients randomized to the SOC arm achieved MRD negativity at the 10-5 threshold, respectively. No new safety signals were observed in the study.

Ninety-seven% and 94% of patients reported grade 3 or 4 adverse events, including infections (27%, 25%) and cytopenias (94%, 86%), respectively. In the CARVYKTI® arm, 76% reported cytokine release syndrome (CRS) (1% grade 3, no grade 4 or 5), five% reported immune effector cell-associated neurotoxicity syndrome (all grade 1 or 2) and one patient had a grade 1 movement and neurocognitive treatment-emergent adverse event (TEAE). Overall, 39 patients in the CARVYKTI® arm and 46 patients in the SOC arms died; 10 CARVYKTI® and five SOC patients passed due to TEAEs.