Carvykti's clinical findings for early lines of multiple myeloma in the CARTITUDE-2 study (cohorts A and B) reaffirm the drug's potential (Abstract # 8029, and 8020)
Carvykti (ciltacabtagene autoleucel, Cilta-cel) is a newly approved CAR-T cell therapy for adults with relapsed or refractory multiple myeloma (FDA approved in February 2022). The findings of the CARTITUDE-2 trial were presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting. The multicohort phase II study (NCT04133636) evaluates the safety and efficacy of Cilta-cel in different myeloma settings, including early lines. Patients in Cohort A include advanced multiple myeloma following 1-3 prior lines of treatment and were lenalidomide-refractory. In contrast, patients in Cohort B had an early relapse after the first therapy that included a proteasome inhibitor and an immunomodulatory medication.
COHORT A-Data (1–3 prior lines of therapy): Abstract #8020
At a median follow-up of 17.1 months, Cilta-Cel produced an overall response rate (ORR) of 95%, with 90% reaching a complete response (CR) or better and 95% achieving a very good partial response (VGPR) or better. The median time to first response was one month, while the median time to best response was 2.6 months. The progression-free survival (PFS) rate after 15 months was 70%. MRD negativity was reached in all 16 patients who were MRD-evaluable at 10-5.
Cohort B Data (patients with early relapse after initial therapy): Abstract #8029
At a median follow-up of 13 months, 19 patients in this cohort had an ORR of 100%, with 90% achieving a CR or higher and 95% achieving a VGPR or better. The median response time was one month, and the median response time was 5.1 months. The PFS rate during 12 months was 90%. 14 of the 15 MRD-evaluable patients attained MRD negative at 10-5.
The overall safety profile of CARTITUDE-2 cohorts, including the incidence of Cytokine Release Syndrome (CRS) and the most prevalent hematologic adverse events (AEs), was comparable with that of CARTITUDE-1.
“We have lots of clinical trials, looking at both the approved CARTs in the earlier line setting, including frontline and then other innovative CAR T strategies. –Expert Opinion
“The follow-up results from the ongoing CARTITUDE-2 Cohort A and B studies support the potential of cilta-cel as a therapeutic option for earlier lines of treatment.” –Expert Opinion.
There have been tremendous breakthroughs in treating multiple myeloma over the previous decade, with the US FDA approving a wide range of treatments. The most recent evidence for bispecific antibodies, not just BCMA, but also other novel markers, such as GPRC5D (G-protein coupled receptor family C group 5 member D), to BCMA-CAR-T Cell therapies, have shown encouraging outcomes in a severely pretreated multiple myeloma patient pool. Many drugs have demonstrated their efficacy in the later-line setting, which is why the emphasis has shifted to earlier lines. Likewise, CAR-T Cell therapies are broadly accepted in the relapsed/refractory patient pool (Abecma and Carvykti have been FDA approved for patients with multiple myeloma who have received four prior lines of therapies), but companies are attempting to broaden their prescription and leverage on the early lines of settings. Cilta-Cel has demonstrated early, substantial, and long-lasting responses in heavily pretreated patients with Multiple Myeloma, leading to United States Food and Drug Administration (FDA) approval. Although Janssen and Legend biotech primarily targeted the later line of multiple myeloma, the CARTITUDE-2 trial ASCO result suggests that CAR-T cell therapy could be offered in early lines. Aside from the CARTITUDE-2 trial [NCT04133636], multiple myeloma therapy companies, J&J and Legend are undertaking extensive research on Cilta-Cel in early-line settings (CARTITUDE-4 [NCT04181827] and CARTITUDE-5 [NCT04923893]) and outpatient settings.
Companies- Oncopeptides, GlaxoSmithKline, Bluebird Bio, Janssen Pharmaceutical, Legend Biotech, AbbVie, Roche (Genentech), Bristol Myers Squibb, Regeneron Pharmaceuticals, Pfizer, Takeda, Amgen, SpringWorks Therapeutics, Adicet Bio, Arcellx, Gracell Biotechnologies, Oricell, Poseida Therapeutics, Precision Biosciences, CRISPR Therapeutics AG, Collectis SA, Allogene Therapeutics, Fortis Therapeutics, Novartis, I-Mab/MorphoSys, Cartesian Therapeutics, CASI Pharmaceuticals, LAVA Therapeutics, and others