The recommendation comes after positive data was released from the recent phase 2 KarMMa trial.
This content originally appeared on our sister site, OncLive.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has made a recommendation for idecabtagene vicleucel's (ide-cel; Abecma) conditional marketing. The treatment has been recommended for use in in adult patients with relapsed and refractory multiple myeloma who have received at least 3 prior therapies, including an immunomodulatory agent (IMiD), a proteasome inhibitor (PI), and a CD38-targeted antibody, and have progressed on their last therapy.1
Data from the recent phase 2 KarMMa trial (NCT03361748) informed the positive opinion. The trial showed that the CAR T-cell therapy elicited an overall response rate (ORR) of 73% in heavily pretreated patients with relapsed/refractory multiple myeloma, at a median follow-up of 24.8 months (range, 1.7-33.6).2
Of those who responded to treatment, 33% achieved a complete response (CR) and 20% had a partial response. Patients who received the product at 150, 300, and 450 million CAR T-cell doses achieved ORRs of 50%, 69%, and 81%, respectively; CR/stringent CR rates at these dose levels were 25%, 29%, and 39%, respectively.
Notably, ORR was not found to vary by previous lines of therapy received. Patients who had received 3 prior lines of therapy (n = 15) achieved an ORR of 73%, and those who received 4 prior lines experienced an ORR of 73%.
“As the first CAR T-cell therapy for relapsed and refractory multiple myeloma to receive a positive CHMP opinion, [ide-cel] represents a potential new treatment approach for patients in Europe battling this incurable blood cancer,” Noah Berkowitz, MD, PhD, senior vice president of Cellular Therapy Development at Bristol Myers Squibb, stated in a press release. “We look forward to the European Commission’s decision as we build on our innovative multiple myeloma and cell therapy research to offer novel and personalized treatment options for patients in need.”
The phase 2 KarMMa trial enrolled patients with relapsed/refractory multiple myeloma who had previously received at least 3 regimens with at least 2 consecutive cycles each or best response of progressive disease. Patients had to have previous exposure to an IMiD, a PI, and a CD38-targeted antibody; they also needed to be refractory to their last therapy received. Of the 140 patients enrolled to the trial, 128 received treatment with the product.
Patients received the CAR T-cell products at 1 of 4 target doses: 150 x 106 CAR+ T cells (n = 4), 300 x 106CAR+ T cells (n = 70), and 450 x 106 CAR+ T cells (n = 54). The CR rates reported across these dose levels were 25%, 29%, and 39%, respectively.
The primary end point of the trial was ORR, and key secondary end points comprised CR rate, duration of response (DOR), progression-free survival (PFS), overall survival (OS), pharmacokinetics, minimal residual disease, quality of life, and safety.
The median age among these patients was 61 years (range, 33-78), 59% were male, 53% had an ECOG performance status of 1, and 70% had R-ISS stage II disease. Moreover, 35% of patients had high-risk cytogenetics and 51% had high tumor burden. The majority, or 85%, of patients had a tumor BCMA expression of at least 50%. Thirty-nine percent of patients had extramedullary disease.
Additionally, the median time since initial diagnosis was 6 years (range, 1-18), and patients had received a median number of 6 prior antimyeloma regimens (range, 3-16). Ninety-four percent of patients underwent prior autologous stem cell transplant, and 34% had undergone more than 1 procedure. Notably, 94% of patients were refractory to a CD38-targeted antibody, 84% were triple refractory, and 26% were penta-refractory.
The baseline characteristics for patients who had received 3 prior lines of treatment (n = 15) proved to be generally comparable to those who had received 4 or more prior lines of therapy (n = 113). Numerical differences were observed with regard to extramedullary disease (47% vs 38%, respectively), high-risk cytogenetics (47% vs 34%), prior refractoriness, and time since initial diagnosis to screening (4 years vs 7 years).
Additional data presented during the 2021 ASCO Annual Meeting showed that the median time to first response was 1.0 month (range, 0.5-8.8) and the median time to CR was 2.8 months (range, 1.0-15.8).
Notably, responses achieved with the CAR T-cell product proved to be durable. The median DOR with ide-cel was 10.9 months (95% CI, 9.0-11.4) among all patients who received ide-cel and increased with depth of response. Among those who received 3 prior lines of treatment, the median DOR was 8.0 months (95% CI, 3.3-11.4) and it was 10.9 months (95% CI, 9.0-11.4) in those who received 4 or more prior lines of therapy.
Across all target doses, the median PFS was 8.6 months (95% CI, 5.6-11.6). In patients who received 3 prior lines of treatment, the median PFS was 8.6 months (95% CI, 2.9-12.1), and it was 8.9 months in those who had received 4 or more prior lines (95% CI, 5.4-11.6).
The median OS among all patients who received ide-cel was 24.8 months (95% CI, 19.9-31.2). Among those who received 3 prior lines or 4 or more prior lines of therapy, the median OS was 22.0 months (95% CI, 10.0–not evaluable [NE]) and 25.2 months (95% CI, 19.9–NE), respectively.
Notably, the median OS was over 20 months in several important high-risk subsets, including those who were aged 65 years or older (28.3 months; 95% CI, 20.2–NE), those with extramedullary disease (20.2 months; 95% CI, 15.5-28.3), and those who were triple refractory (21.7 months; 95% CI, 18.2–NE).
The safety profile of the CAR T-cell product was consistent with what has previously been reported. Incidence of cytokine release syndrome (CRS) and neurotoxicity were consistent with prior reports and were comparable between those who had 3 or 4 or more prior lines of therapy. Eighty-four percent of patients experienced at least 1 CRS event and 78% of these cases were either grade 1 or 2. Moreover, 18% of patients reported neurotoxicity with the product.
Additionally, similar rates of infections and second primary malignancies were reported, and no unexpected gene therapy–related adverse effects were noted with longer follow-up.
In March 2021, the FDA approved ide-cel as the first BCMA-directed CAR T-cell therapy for patients with relapsed/refractory multiple myeloma following 4 or more prior lines of therapy, including an IMiD, a PI, and an anti-CD38 monoclonal antibody.3 The decision was supported by earlier data from KarMMA.