FDA Approval Sought for Ide-cel in Relapsed/Refractory Multiple Myeloma

A Biologics License Application has been submitted to the FDA for the investigational B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cell immunotherapy idecabtagene vicleucel (Ide-cel, bb212) as treatment of patients with multiple myeloma who have received at least 3 prior therapies, which should include an immunomodulatory (IMiD) agent, a proteasome inhibitor (PI), and an anti-CD38 antibody, Bristol Myers Squibb announced in a press release.¹

The BLA is supported by results from the phase II KarMMa study, which is evaluating the safety and efficacy of Ide-cel in patients with relapsed/refractory multiple myeloma.

Topline results from the study were announced in December 2019. The results showed that Ide-cel elicited deep and durable responses, achieving its primary end point of overall response rate (ORR).²

Out of 140 patients, 120 were given the target dosage of Ide-cel (150-450 x 10⁶). The patients enrolled were heavily pretreated and had received a prior IMiD agent, PI, and an anti-CD38 antibody agent, and were refractory to their previous regimen. Overall, 94 patients were refractory to an anti-CD38 antibody, and 84% of patients were triple refractory.

At a median follow-up of 28 months, the ORR was 73.4% in patients who received the target dose, which led to complete responses (CRs) in 40 patients (31.3 %). The median duration of response (DOR) was 10.6 months, and the median progression-free survival (PFS) was 8.6 months.

At the next dose level (450 x 10⁶), the ORR was 81.5% with 19 patients (35.2%) achieving a CR. The DOR and PFS in this group were both 11.3 months. Among patients who were given a 300 x 10⁶dose of CAR T cells, the ORR was 68.6% with 20 patients (28.6%) achieving a CR. The DOR in this group was 9.9 months, and the PFS was 5.8 months. At the lowest dose level (150 x 10⁶), the ORR was 50.0%, and a CR was observed in 1 patient (25%). The DOR and PFS were not reached in this group.

The safety profile observed in the KarMMa study was consistent with safety observed in a prior phase I study CRB-401 study, which was assessing the incidence of adverse events (AEs) in patients with relapsed/refractory multiple myeloma being treated with Ide-cel.

In KarMMa, 5.5% of patients experienced grade higher cytokine release syndrome (CRS). One of the CRS events was fatal. Grade 3 or higher neurotoxicity events occurred in 3.1% of patients. Less than 6% of patients among each dose level of CAR T-cell therapy had grade 3 or higher CRS or neurotoxicity events. Overall, any-grade CRS occurred in 83.6% of the study population (n =107), and any-grade neurotoxicity events occurred in 18% of the patients (n = 23).

KarMMa is an ongoing multicenter study being conducted in Japan. The secondary end points being evaluated include CR, time to response, DOR, PFS, overall survival, AEs, and pharmacokinetics.

To be eligible for the trial, patients must be at least 18 years of age with a documented diagnosis of multiple myeloma, an ECOG performance status of 0 or 1, and measurable disease. The study excluded individuals with known central nervous system (CNS) involvement with myeloma, active or prior plasma cell leukemia, solitary plasmacytomas or non-secretory myeloma without other evidence of measurable disease, inadequate organ function, evidence of infection related to human immunodeficiency virus, evidence of active viral infection with hepatitis B virus or hepatitis C virus, history of class III or IV congestive heart failure, hypersensitivity to any component of Ide-cel, a second malignancy in addition to myeloma, and those who known CNS involvement with myeloma or a history of CNS pathology.

Ide-cel was granted Breakthrough Therapy Designation by the FDA for relapsed/refractory multiple myeloma. The drug also has a designation in Europe.¹

References

1. Bristol Myers Squibb and bluebird bio announce submission of biologics license application (bla) for anti-bcma car t cell therapy idecabtagene vicleucel (ide-cel, bb2121) to fda [new release]. Princeton, New Jersey and Cambridge, Massachusetts: Bristol Myers Squibb; March 31, 2020.https://bit.ly/2JwKbxO. Accessed March 31, 2020.
2. Bristol-Myers Squibb and bluebird bio announce positive top-line results from the pivotal phase 2 KarMMa study of ide-cel in relapsed and refractory multiple myeloma [news release]. Princeton, New Jersey and Cambridge, Massachusetts: Bristol Myers Squibb; December 6, 2019.https://bit.ly/3bDtqgE. Accessed March 31, 2020.