Phase 3 KarMMa-3 Trial Meets Primary End Point of PFS With Ide-Cel in R/R Multiple Myeloma

At the pre-specified interim analysis, the phase 3 KarMMa-3 trial (NCT03651128) met its primary end point of statistically significantly improved progression-free survival when patients with relapsed/refractory multiple myeloma who had previously received 2 to 4 prior lines of therapy and were refractory to their last regimen were treated with idecabtagene vicleucel (ide-cel; Abecma) compared with standard of care (SOC), according to a press release from Bristol Myers Squibb and 2seventy bio.¹

The interim analysis also showed improvement in the key secondary end point of overall response rate vs SOC. Additional data will be presented at an upcoming medical meeting.

Ide-cel was designed as a first-in-class B-cell maturation agent-directed CAR T cell immunotherapy. It may also be used as an immunomodulatory agent, proteasome inhibitor, or and anti-CD-38 antibody.

“Results from the KarMMa-3 study clearly demonstrate the clinical benefit of using a CAR T cell therapy earlier in the multiple myeloma treatment paradigm,” Anne Kerber, senior vice president, head of Cell Therapy Development at Bristol Myers Squibb, said in the press release. “These data reinforce our commitment to unlocking the full potential of cell therapy as we strive to build on the company’s heritage of innovation in blood cancers and transform patients’ lives through science.”

The randomized, open-label trial study had an estimated enrollment of 381 patients. The SOC regimen consisted of daratumumab (Darzalex), pomalidomide (Pomalyst), dexamethasone, bortezomib (Velcade), ixazomib (Ninlaro), lenalidomide (Revlimid), carfilzomib (Kyprolis) or elotuzumab (Empliciti). Additional secondary end points included overall survival, event-free survival, minimal residual disease, complete response rate, and duration of response.

In terms of safety, investigators reported that cytokine release syndrome (CRS) occurred in 85% of patients who were treated with ide-cel; of these, 9% of events were grade 3, and 0.8% were grade 5. Median time to onset of CRS was 1 day and it lasted a median of 7 days. Neurologic toxicities were also observed in 28% of patients in the experimental arm, with 4% experiencing grade 3 events. Neurotoxicity associated with CAR T-cell therapy treatment resolved in 92% of patients and lasted a median of 5 days. Moreover, neurotoxicity lasted a median duration of 6 days in the overall patient population. A total of 34 patients had both neurotoxicity had CRS. A total of 70% of patients experienced infections of any grade; in particular, 23% had grade 3/4 infections. Moreover, 1.6% of patients had grade 5 pneumonia, 0.8% had bronchopulmonary aspergillosis, and cytomegalovirus pneumonia associated with Pneumocystis jirvecii (0.8%).

Patients were eligible for treatment if they had measurable and documented disease, received 2 but no more than 4 prior regimens, and underwent prior treatment with daratumumab for at least 2 consecutive cycles. Additionally, patients were required to be refractory to the last treatment received and have an ECOG performance status of 0 or 1.

Exclusion criteria included having prior conditions that would prevent the patient from participating in the study, laboratory abnormalities, and any condition that could make it challenging to interpret data. Patients were also not able to have nonsecretory multiple myeloma, inadequate pulmonary function, a prior history of malignancies other than the disease being treated, and needed to be free from prior malignancies for 5 or more years.

In March 2021, the FDA approved ide-cel for patients with relapsed/refractory multiple myeloma who had received 4 or more lines of therapy.² The approval was based on results from the phase 2 KarMMa trial (NCT03361748).³

References

1. Bristol Myers Squibb and 2seventy bio announce topline results from KarMMa-3 trial showing Abecma (idecabtagene vicleucel) significantly improves progression-free survival versus standard regimens in relapsed and refractory multiple myeloma. News Release. Bristol Myers Squibb. August 10, 2022. Accessed August 30, 2022. https://bit.ly/3RlgNvz
2. FDA approves idecabtagene vicleucel for multiple myeloma. News Release. FDA. March 26, 2021. Accessed August 30, 2022. https://bit.ly/3ecb6C0
3. Munshi NC, Anderson LD Jr, Shah N, et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N Engl J Med. 2021;384(8):705-716. doi:10.1056/NEJMoa2024850