Novel CAR-T Cell Therapy Shows Promise in Heavily Pretreated Relapsed/Refractory Multiple Myeloma


After a median follow-up of 13.3 months, the median overall response rate across all patients who received idecabtagene vicleucel (ide-cel) was 73%, including a complete response of 33%.

Data from the phase 2 KarMMA trial presented during the 2020 ASCO Virtual Scientific Program show that idecabtagene vicleucel (ide-cel), a novel CAR T-cell therapy which targets the B-cell maturation antigen (BCMA), demonstrated durable responses in patients with heavily pretreated relapsed/refractory multiple myeloma.

“(The) outcome of patients with triple-exposed relapsed refractory myeloma is poor, with infrequent deep and durable responses and median (progression-free survival) of three to four months,” said Dr. Nikhil C. Munshi, director of basic and correlative science in the Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute, during a presentation of the data. “Previous results … (of a) ide-cel-utilizing study in relapsed refractory myeloma were very encouraging, with overall response rate of 85% and duration of response of 10.9 months, with tolerable toxicity profile. Based on this, here we have evaluated efficacy and safety of ide-cel in relapsed refractory myeloma.”

The phase 2 trial comprised 128 patients (with a median age of 61 years) with relapsed/refractory multiple myeloma who received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody.

Fifty-one percent of the patients presented with a high tumor burden, 35% of patients had high-risk cytogenetics, 39% had extramedullary disease and 85% had a 50% or greater expression of BCMA.

Almost all patients (94%) received a previous autologous stem cell transplant, and 34% received more than one. Eighty-eight percent of patients received bridging therapies while the CAR T-cell was being manufactured. However, only 4% of patients responded to that treatment.

Patients within the study were treated with either 150 million cells (4 patients), 300 million cells (70 patients) or the targeted dose of 450 million cells (54 patients).

Overall response rate (ORR) was the study’s main outcome. Additional secondary outcomes included complete response, duration of response, progression-free survival, overall survival and quality of life.

After a median follow-up of 13.3 months, the median ORR across all patients who received ide-cel was 73%, including a complete response of 33%. The median time to a first response was one month and the median time to a complete response was 2.8 months.

The median duration of response across all patient groups was 10.7 months, and the median progression-free survival was 8.8 months.

Patients who received the target dose achieved an ORR of 82%. Additionally, median PFS increased as the dose was increased, reaching 12.1 months in those who received the target dose. At the time of the analysis, median overall survival was 19.4 months and one-year overall survival rate was 78%. However, as Munshi noted during the presentation, survival data are immature.

Overall, 84% of patients experienced at least one cytokine release syndrome (CRS) event, with the majority (78%) considered less severe and less serious. Median time to the start of a CRS event was one day and the median duration of CRS was five days. More than half of the patients (52%) received Actemra (tocilizumab) to manage their CRS, while 15% received corticosteroids.

One or more neurotoxic events occurred in 18% of the overall patient population. Additionally, 91% of the overall patient population had neutropenia and 63% experienced thrombocytopenia.

Five patients died within eight weeks of receiving ide-cel, two of which were a result of the progression of myeloma and the other were related to side effects.

“To conclude, ide-cel demonstrated frequent, deep, and durable responses in heavily pretreated, highly refractory relapsed myeloma patients in this pivotal KarMMa study,” said Nikhil. “Overall, ide-cel provides an attractive and excellent option for treatment of triple-class exposed multiple myeloma.”

Earlier this year, the codevelopers of ide-cel submitted a Biologics License Application (BLA) — which is a request to introduce a therapy to the public — to the Food and Drug Administration (FDA) for the use of the CAR T-cell therapy as a treatment for adults with multiple myeloma who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody.

However, in May, the agency did not file the request for the BLA citing that it concluded that additional information regarding the chemistry, manufacturing and control was needed. The FDA, according to the codevelopers, did not ask for any further clinical or nonclinical data.

A version of this story originally appeared on OncLive® as “Idecabtagene Vicleucel Highly Active in Heavily Pretreated Myeloma.”

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