Long-Term Data Show Cilta-Cel Yields Early, Durable Responses in Relapsed Refractory Multiple Myeloma

Take-aways:

• At 18-month follow-up, a single dose of ciltacabtagene autoleucel led to early, deep, and durable responses in heavily pretreated patients.
• Nearly all patients experienced cytokine release syndrome, and there were no new incidences of neurotoxicity or neurocognitive treatment-emergent adverse events.
• Several patient management strategies, such as enhanced bridging therapy and aggressive treatment of toxicities, have been introduced into the CARTITUDE study program.

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In patients with relapsed/refractory multiple myeloma, a single infusion of ciltacabtagene autoleucel (cilta-cel) produced deep and durable responses and was associated with manageable safety outcomes. Saad Z. Usmani, MD, FACP, from Memorial Sloan Kettering Cancer Center in New York, shared these long-term findings from the CARTITUDE-1 study at the 2021 Society of Hematologic Oncology Annual Meeting.

Cilta-cel is a chimeric antigen receptor (CAR) T-cell therapy with 2 B-cell maturation antigen (BCMA)–targeting single-domain antibodies. In the phase Ib/II CARTITUDE-1 trial, 97 patients with relapsed/refractory multiple myeloma were treated with a cilta-cel infusion (0.75 × 10⁶ CAR+ T cells/kg). Treatment was infused following cyclophosphamide/fludarabine lymphodepletion. The researchers characterized safety of the single targeted dose of cilta-cel and sought to evaluate the efficacy of the recommended phase II dose established in the phase Ib portion of the study.

Previous research had reported findings from a median follow-up of 12.4 months. The present analysis extends follow-up to 18 months. Patients in the longer-term follow-up analysis of the CARTITUDE-1 study had received a median of 6 prior lines of therapy. Approximately 90% of patients had undergone a prior autologous stem cell transplantation, while most of the remaining patients (8.2%) had previously received an allogeneic transplantation. The median age of the population was 61 years (range, 43-78). More than half (58.8%) of the population was male, and nearly 24% of patients had a high-risk cytogenetic profile, defined as presence of del17p, t(14;16), and t(4;14). Tumor BCMA expression greater than 50% was reported in 91.9% of patients.

The overall response rate was 97.9%, with 80.4% of patients experiencing a stringent complete response (CR). The median time to first response was 1 month (range, 0.9-10.7), while the time to CR or better was 2.6 months (range, 0.9-15.2). Overall, the median duration of response was 21.8 months, but the researchers noted that an estimated 73% of responders had not progressed or died at 12-month follow-up. In addition, the median duration of response had not been reached in the subpopulation with stringent CR.

The investigators added that response rates were comparable, ranging between 95% and 100% across different subgroups (e.g., previous lines of therapy, refractoriness, cytogenetic risk).

These responses appeared to deepen over time. In the 61 patients who were evaluable for measurable residual disease (MRD), most patients (91.8%) were MRD-negative (with a sensitivity of 10^-5).

Regarding survival, the median progression-free survival (PFS) among all 97 patients was 22.8 months (range, 22.8 months to not estimable). In the group of patients who achieved at least a stringent CR, median PFS had not been reached. The 18-month PFS rate was 66% among all patients and 75.9% among those in stringent CR or better. In addition, the 18-month overall survival (OS) rate was 80.9%.

The most common grade 3/4 hematologic adverse events (AEs) reported in the cohort included neutropenia (94.8%), anemia (68%), leukopenia (60.8%), thrombocytopenia (59.8%), and lymphopenia (49.5%). The CAR T-cell therapy–associated toxicity cytokine release syndrome (CRS) was reported in nearly all patients (94.8%), and the median time to onset of CRS events was 7 days (range, 1-12). Approximately one-fifth of patients experienced CAR T cell–related neurotoxicity, including 10.3% who had grade >3 neurotoxicity. Overall, though, the researchers noted that there were no new incidences of neurotoxicity or neurocognitive treatment-emergent AEs.

The investigators described several patient management strategies that have been introduced into the CARTITUDE study program to mitigate the incidence of neurotoxicity and other AEs. Some of the cited patient management strategies included enhanced bridging therapy to reduce tumor burden, as well as early and aggressive treatment of CRS and immune effector cell–associated neurotoxicity syndrome.

During the study, a total of 14 patients died, including 2 within 100 days following infusion. In general, deaths were most commonly due to disease progression (n, 5) or treatment-related AEs (n, 4).

The investigators noted that cilta-cel is now undergoing investigation in the ongoing phase II CARTITUDE-2 and phase III CARTITUDE-4 studies, which are evaluating the therapy earlier during treatment.

Disclosures: This research was supported by Janssen Research & Development and Legend Biotech. Study authors report financial relationships with Janssen Research & Development and Legend Biotech.

Reference

Usmani SZ, Berdeja JG, Madduri D, et al. Updated results of ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen (BCMA)–directed chimeric antigen receptor T (CAR-T) cell therapy, in relapsed/ refractory multiple myeloma (RRMM). Abstract #MM-119. Presented at the 2021 Society of Hematologic Oncology, September 8-11, 2021.