Bristol Myers Squibb (BMS) and 2seventy bio have announced the discontinuation of enrollment in the Phase 3 KarMMa-9 trial, which was investigating Abecma (idecabtagene vicleucel) in combination with lenalidomide maintenance versus lenalidomide maintenance alone for patients with newly diagnosed multiple myeloma (NDMM) who have suboptimal response after autologous stem cell transplant. The decision comes after facing significant enrollment challenges due to the rapidly evolving treatment landscape in NDMM.
The KarMMa-9 trial, which has been open for over a year across 18 countries, has only managed to enroll 10% of its planned study population. This shortfall is attributed to the increasing effectiveness of initial induction therapies, which now lead to a complete response or better in a significant majority – upwards of 70% – of patients with NDMM following transplant.
Impact of Evolving Treatment Landscape
According to Anne Kerber, senior vice president, head of late clinical development, haematology, oncology and cell therapy (HOCT), Bristol Myers Squibb, the advances in induction therapies have dramatically changed the landscape. "Investigators indicate that due to advances in induction therapies, a significant majority – upwards of 70% – of patients with newly diagnosed multiple myeloma are now achieving a complete response or better following transplant," Kerber stated. This progress, while positive for patients, has reduced the eligible patient population for the KarMMa-9 trial.
The trial was initially designed based on promising data from cohort 2c of the KarMMa-2 trial, which showed a favorable benefit/risk profile for Abecma in a similar patient population. However, the introduction of more intense and prolonged induction therapies has altered the treatment paradigm, leading to fewer patients with the suboptimal response required for KarMMa-9 enrollment.
Abecma's Role in Multiple Myeloma Treatment
Abecma is a CAR T-cell therapy that targets BCMA on multiple myeloma cells, triggering an immune response that leads to the destruction of these cells. It received FDA approval in April 2024 for treating adult patients with relapsed or refractory multiple myeloma after two or more prior lines of therapy, including an immunomodulatory agent (IMiD), a proteasome inhibitor (PI), and an anti-CD38 monoclonal antibody. This approval expanded Abecma's indication to earlier lines of treatment based on the Phase 3 KarMMa-3 trial results.
Next Steps for KarMMa-9 Patients
BMS and 2seventy bio are collaborating with investigators to determine the appropriate next steps for patients currently enrolled in the KarMMa-9 study. Both companies have expressed gratitude to the patients, investigators, and study staff involved in the trial.
Anna Truppel-Hartmann, chief medical officer at 2seventy bio, acknowledged the progress in NDMM treatment. "Since we initiated the Phase III KarMMa-9 study in NDMM based on the positive data generated in a similar patient population in the KarMMa-2 cohort 2c study, the NDMM treatment landscape has improved considerably with the increasing use of quadruplet therapy induction, incorporation of more aggressive consolidation therapies, and the ongoing optimization of maintenance therapy regimens," she said. Truppel-Hartmann added that the company will continue to focus on serving patients with a high unmet need who will benefit most from Abecma.
Commitment to Multiple Myeloma Research
Despite discontinuing enrollment in KarMMa-9, Bristol Myers Squibb remains committed to advancing the science in multiple myeloma. The company is actively recruiting patients for several other studies across its cell therapy and protein degradation pipeline.
