CARTITUDE-1 Update: Cilta-Cel Maintains Benefit in R/R Multiple Myeloma


At a prespecified analysis of the CARTITUDE-1 trial with a median follow-up of approximately 28 months, treatment with cilta-cel continued to elicit positive responses and maintained a favorable risk/benefit profile for patients with multiple myeloma.

Patients with relapsed/refractory multiple myeloma (RRMM) in standard and high-risk subgroups treated with ciltacabtagene autoleucel (cilta-cel; Carvykti) had deep and durable responses, and the risk/benefit profile of cilta-cel remained favorable with longer follow-up, according to updated findings from the phase 1b/2 CARTITUDE-1 study (NCT03548207).

Previous data from CARTITUDE-1, a phase 1b/2 trial which assessed the safety and efficacy of cilta-cel in heavily pretreated patients with RRMM, demonstrated early, deep, and durable responses with the agent at 12 months.

These updated results with a median follow-up of approximately 28 months, including analyses of high-risk patient subgroups, now have revealed the overall response rate (ORR) at a median follow-up of 27 months to be 97.9% (95% CI, 92.7-99.7), and 2.5% (95% CI, 73.4-89.4) of patients achieved a stringent complete response (sCR). The safety profile of the agent was also manageable for this patient population.

“This prespecified analysis of the CARTITUDE-1 trial at 28 months [median follow-up] demonstrates the sustained clinical benefit of cilta-cel in patients with RRMM who had received a median of 6 prior [lines of therapy]. As median PFS has not yet been reached, clinical benefit continues for many patients. Responses to a single infusion of cilta-cel deepened from 67% with sCR at 12-month [median follow-up] to 82.5% at 28 months. Response depth and durability were related, as illustrated by the higher rates of PFS in patients with sCR and/or sustained MRD negativity,” wrote study authors in findings published in The Journal of Clinical Oncology.

The single-arm, open-label, multicenter, phase 1b/2 CARTITUDE-1 study included patients who had received ≥ 3 prior lines of therapy, including a protostome inhibitor (PI), IMiD, and an anti-CD38 antibody, or who were double refractory to PI and IMiD and had received an anti-CD38 antibody. Patients must also have had evidence of progressive disease (PD) within 12 months of the last line of therapy.

The trial administered a single cilta-cel infusion at a target dose 0.75 × 106 CAR-positive viable T cells/kg; range, 0.5-1.0 × 106 5-7 days after lymphodepletion (300 mg/m2 cyclophosphamide, 30 mg/m2 fludarabine once daily for 3 days). Patients were permitted to be retreated with cilta-cel in the same dose range if they had documented PD ≥ 6 months after cilta-cel infusion with best response of at least minimal response who had no ongoing hematologic (grade ≥ 3) or nonhematologic (grade ≥ 2) toxicities.

The primary end point of the phase 2 portion of the study was ORR. Secondary end points included rates of sCR, complete response (CR), very good partial response, minimal residual disease (MRD) negativity, duration of response (DOR), progression-free survival (PFS), and overall survival (OS).

Sixty-six of the 97 patients who received cilta-cel infusion remained on study as of the data cutoff date of January 11, 2022. The median time from receipt of the apheresis material to release of cilta-cel was 29 days (interquartile range (IQR), 28-33), and all patients treated with cilta-cel were administered a dose within the target range. Baseline characteristics showed that those enrolled had received a median of 6 (range, 3-18) prior lines of therapy, and among the 96 patients with evaluable bone marrow biopsy and/or aspirate samples, 21.9% had high disease burden (≥ 60% plasma cells). Additionally, 19 patients (19.6%) had plasmacytomas detected at screening.

All 97 patients who were given cilta-cel were included in the efficacy analyses. Updated efficacy findings revealed that at a median follow-up of 27.7 months, the ORR was 97.9%, the sCR rate was 82.5%, the very good partial response rate was 12.4%, and the PR rate was 3.1%. No patient had only a CR only. The median time to first response was 1 month, the median time to best response was 2.6 months, and the median time to CR or better was 2.9 months.

Neither the median DOR and median PFS were reached, and the time point at which 75% of patients were progression-free (75th percentile) was 12.9 months (95% CI, 6.9-18.04). At 27-months, PFS and OS rates were 54.9% (95% CI, 44.0 to 64.6) and 70.4% (95% CI, 60.1 to 78.6), respectively. Across all subgroups (range, 95.1%-100%), the ORR was high. Moreover, the DOR, PFS, and OS were shorter in patients with high-risk cytogenetics, International Staging System stage III, high tumor burden, or plasmacytomas.

Looking at safety, treatment with cilta-cel was manageable and no new cilta-cel-related cytokine release syndrome were seen. There was 1 new case of parkinsonism (day 914 after cilta-cel) since the last report. The most common grade 3/4 treatment-emergent AEs (TEAEs) were hematologic, grade 3/4 thrombocytopenia occurred in 60 patients, 20 patients (33.3%) had recovered to grade ≤ 2 by day 30, and 35 (58.3%) recovered by day 60. Neutropenia which was grade 3/4 was observed in 95 patients, but 66 (69.5%) had recovered to grade ≤ 2 by day 30 and 85 (89.5%) by day 60. Grade 3/4 lymphopenia was reported in 96 patients with 84 (87.5%) recovering to grade ≤ 2 by day 30 and 88 (91.7%) by day 60.

“[T]hese longer-term data from CARTITUDE-1 in triple-class exposed patients with RRMM demonstrate deep and durable responses to cilta-cel over time, including in high-risk subgroups. The safety profile continues to be manageable. The recent approval of cilta-cel in the [United States] and positive CHMP opinion by the EMA will help fill an unmet medical need in this difficult-to-treat population,” concluded the study authors.

Martin T, Usmani SZ, Berdeja JG, et al. Ciltacabtagene autoleucel, an anti-B-cell maturation antigen chimeric antigen receptor T-cell therapy, for relapsed/refractory multiple myeloma: CARTITUDE-1 2-Year Follow-Up. J Clin Oncol. 2023;41(6):1265-1274. doi:10.1200/JCO.22.00842
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