Early Relapse Multiple Myeloma Cohort Shows Deepened Responses to Cilta-Cel

Tessa Kerre, MD, PhD

Associate Professor

Faculty of Medicine and Health Sciences

Ghent University

Ghent, Belgium

Ciltacabtagene autoleucel (Cilta-cel; Carvykti) showed durable responses and a 100% overall response rate (ORR) in early relapsed patients with multiple myeloma (MM), according to updated results from the CARTITUDE-2 trial (NCT04133636), which were presented at the European Society for Blood and Marrow Transplantation (EBMT) 49th Annual Meeting.¹

Ninety percent of CARTITUDE-2 patients (all of whom had previously relapsed within 12 months of initial therapy) achieved at least a complete response (CR) to cilta-cel, and 83% remained alive and progression free. These results support the use of chimeric antigen receptor (CAR) T-cell therapy earlier in therapy than is currently approved.

“The median survival of patients with multiple myeloma who experienced an early clinical relapse on the frontline therapy is less than 2 years,” said Tessa Kerre, MD, PhD, associate professor at Ghent University in Belgium, in the presentation.

Cilta-cel is a CAR T-cell therapy that targets B-cell maturation antigen (BCMA). CARTITUDE-2 is a multicohort phase 2 study. One cohort (B) enrolled patients with MM who had received a PI and IMiD and had progressed within 12 months of autologous stem cell transplant (ASCT) or within 12 months of starting therapy if they had not undergone ASCT. Initially, patients received bridging therapy as needed after apheresis and before lymphodepleting chemotherapy and cilta-cel.

The primary end point was minimal residual disease (MRD) negativity at a 10^-5 threshold assessed by next-generation sequencing or next-generation flow. Secondary end points included ORR, duration of response, time to response, and incidence and severity of such adverse events (AEs) as cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS).

Analysis of cohort B at a median follow-up of 13.4 months showed an ORR of 100%, with 95% of patients achieving a very good partial response (VGPR) or better.²

As of June 2022, 19 patients in this cohort were evaluated at median follow-up of 18.0 months (range, 5.2-26.3).¹ Fifteen (78.9%) had received prior ASCT, and 3 (15.8%) had high-risk cytogenetics. Fifteen patients (78.9%) had been refractory to their last line of therapy and 3 (15.8%) had triple-class refractory MM.

At the longer follow-up, responses deepened. All patients achieved VGPR or better: 68% experienced stringent CR, 21% CR, and 11% VGPR. The median time to first response was 0.95 months (range, 0.9-9.7), and the median time to best response was 5.09 months (range, 0.9-11.8). Median duration of response was not reached.

Fifteen patients were evaluable for MRD status at 10-5, 14 of whom (93.3%) were MRD negative. Of those with high-risk cytogenetics, 2 out of 3 were MRD negative.

Three patients died due to progressive disease, but none had progressive disease at 18 months. Median progression-free survival (PFS) and overall survival (OS) had not been reached at this point; the 18-month PFS rate was 83% (95% CI, 55.9-94.3), and the 18-month OS rate was 83% (95% CI, 55.7-94.2).

Grade 3 and 4 cytopenias occurred, including neutropenia (90%), anemia (47%), lymphopenia (47%), thrombocytopenia (26%), and leukopenia (32%). By day 60, anemia and leukopenia had reduced to grade 2 or lower, except for thrombocytopenia (in 16%), lymphopenia, and neutropenia (in 11% each).

Although CRS occurred in 16 of the 19 patients (84%), there was only 1 grade 4 event and no grade 3 events. Tocilizumab (Actemra) was administered to 12 patients (63%) and corticosteroids to 4 (21%). The median time to onset of CRS was 8 days, and its duration was 3.5 days. One patient experienced grade 1 ICANS that lasted 4 days.

Other neurotoxicities were observed in 4 patients, 1 of whom had parkinsonism (grade 3 or higher) that occurred at day 38 and has not resolved. This patient also had high-grade CRS but achieved a CR. There were no AE-related deaths. Two of the 3 patients who died due to progressive disease had high-risk cytogenetics.

Kerre also presented an analysis of the CAR+ T cells in patients. The peak expansion of these cells occurred on day 13 (range, 9.8-14.8). The median persistence of CAR T cells was 76 days (range, 26.9-273.1). The ratio of CD4/CD8 CAR+ T cells was stable at around 1:1 post cilta-cel infusion. “The expansion and the persistence profile of the CAR T cells…[are] very similar to…[those observed in] CARTITUDE-1,” she said, adding that the agent’s efficacy and safety are “promising and…support…[its] continued evaluation…in earlier lines of treatment.”

REFERENCES

1. van de Donk NWJC, Agha ME, Cohen AD, et al. Cartitude-2 cohort B 18-month follow-up: ciltacabtagene autoleucel (cilta-cel), a BCMA-directed CAR T-cell therapy, in patients with multiple myeloma (MM) and early relapse after initial therapy. Presented at: 49th European Society for Blood and Marrow Transplantation (EBMT) Annual Meeting; April 2326, 2023; Paris, France. OS02-03.

2. van de Donk NWJC, Agha ME, Cohen AD, et al. Biological correlative analyses and updated clinical data of ciltacabtagene autoleucel (cilta-cel), a BCMA-directed CAR-T cell therapy, in patients with multiple myeloma (MM) and early relapse after initial therapy: CARTITUDE-2, cohort B. J Clin Oncol. 2022;40(suppl 16):8029. doi:10.1200/JCO.2022.40.16_ suppl.8029