Treatment with the BCMA-targeted CAR T-cell therapy idecabtagene vicleucel was associated with a 73.4% overall response rate in patients with relapsed/refractory multiple myeloma, meeting the primary endpoint of the pivotal phase II KarMMA trial.
Kristen Hege, MD, senior vice president, Hematology/Oncology and Cell Therapy, Early Clinical Development for Bristol-Myers Squibb
Kristen Hege, MD
Treatment with the BCMA-targeted CAR T-cell therapy idecabtagene vicleucel (ide-cel; bb2121) was associated with a 73.4% overall response rate (ORR) in patients with relapsed/refractory multiple myeloma, meeting the primary endpoint of the pivotal phase II KarMMA trial (NCT03361748).1
The topline results showed that across the target dose levels of 150 to 450 x 106 CAR T cells, the complete response (CR) rate was 31.3%, the median duration of response (DOR) was 10.6 months, and the median progression-free survival (PFS) was 8.6 months. Additional findings will be presented at an upcoming medical meeting.
"For multiple myeloma patients who have relapsed and become refractory to current treatment options, there remains a high unmet need, as these patients typically experience low response rates, short response durations and poor survival," Kristen Hege, MD, senior vice president, Hematology/Oncology and Cell Therapy, Early Clinical Development for Bristol-Myers Squibb, which co-develops ide-cel with bluebird bio, stated in a press release. "The KarMMa study provides further support for ide-cel as a potential therapeutic option in this heavily pre-treated patient population, and we are encouraged by these data, especially the outcomes observed at the highest target dose of 450 x 106 CAR+ T cells. We are actively preparing for submission of these data to Health Authorities for proposed initial registration of ide-cel as a first-in-class BCMA-targeted CAR T cell therapy."
Ide-cel is a BCMA-targeting CAR T cell therapy, which is expressed on the surface of normal and malignant plasma cells. In November 2017, the FDA granted breakthrough therapy designation to ide-cel based on the preliminary data from the phase I CRB-401 trial.
In updated findings of the phase I CRB-401 trial, ide-cel induced a median PFS of 11.8 months and a median DOR of 10.8 months in heavily pretreated patients with relapsed/refractory disease.2 Additionally, the ORR was 95.5%, the CR or stringent CR rate was 50%, and 36.4% of patients had a very good partial response. In contrast, patients treated with an inactive dose (50 x 106) had an ORR of 33.3% and a 1.9-month median duration of response.
In the open-label, single-arm, multicenter, phase II KarMMa trial, investigators evaluated the efficacy and safety of ide-cel in patients with relapsed/refractory multiple myeloma in North America and Europe. A total 140 patients were enrolled, and 128 patients were treated with the agent across the target dose levels: 150 x 106 CAR T cells (n = 4), 300 x 106 CAR T cells (n = 70), and 450 x 106 CAR T cells (n = 54).
All patients who received treatment had received ≥3 prior therapies, including an immunomodulatory agent, proteasome inhibitor, and a CD38-directed antibody; all patients were refractory to their last regimen. A total 94% of patients were refractory to a CD38-directed antibody while 84% of patients were refractory to all 3 classes of agents.
The primary endpoint was ORR as assessed by an independent review committee according to International Myeloma Working Group criteria, and the key secondary endpoint was CR rate; additional secondary endpoints overall survival, minimal residual disease, and also DOR and PFS across the target dose levels and at each of the 3 target doses.
At a median follow-up of 11.3 months, results showed that for patients treated at the 150 x 106 CAR T-cell dose, the ORR was 50.0% with a 25% CR rate; the median DOR and PFS were not reported due to the small number of evaluable patients. In the 300 x 106 CAR T-cell cohort, the ORR was 68.6%, along with a 28.6% CR rate; the median DOR was 9.9 months, and the median PFS was 5.8 months. Finally, at the 450 x 106 dose, the ORR was 81.5%, the CR rate was 35.2%, and the median DOR and PFS were both 11.3 months.
Regarding safety, the results were consistent with what was observed in the phase I CRB-401 trial. Grade ≥3 cytokine release syndrome (CRS) occurred in 5.5% of patients, and 1 death occurred due to a CRS event; grade ≥3 neurotoxicity events occurred in 3.1% of patients; no grade 4 events were reported. Additionally, grade ≥3 CRS and neurotoxicity events were reported in <6% of each target dose. All-grade CRS and neurotoxicity events occurred in 83.6% and 18% of patients, respectively.