'Phenomenal' Results with CAR T-Cells in R/R Multiple Myeloma

Roxanne Nelson, RN, BSN

March 02, 2021

Patients with multiple myeloma that has continued to progress despite many lines of therapy have shown deep and durable responses to a new chimeric antigen receptor (CAR) T-cell therapy, idecabtagene vicleucel (ide-cel, under development by Bristol-Myers Squibb and Bluebird Bio).

An expert not involved in the trial described the results as "phenomenal."

Krina Patel, MD, an associate professor in the Department of Lymphoma/Myeloma at the University of Texas MD Anderson Cancer Center, Houston, said that "the response rate of 73% in a patient population with a median of 6 lines of therapy, and with one-third of those patients achieving a deep response of complete response or better, is phenomenal."

"We are very excited as a myeloma community for this study of idecabtagene vicleucel for relapsed refractory patients," Patel said.

The new data on ide-cell, from a trial in 128 patients, were published February 25 in the New England Journal of Medicine.

Lead investigator of the study Nikhil Munshi, MD, of Dana-Farber Cancer Institute, Boston, Massachusetts, commented: "The results of this trial represent a true turning point in the treatment of this disease. In my 30 years of treating myeloma, I have not seen any other therapy as effective in this group of patients."

Both experts highlighted the poor prognosis for this population of relapsed/refractory patients. Recent decades have seen a flurry of new agents for myeloma, and there are now three main classes of agents: immunomodulatory agents, proteasome inhibitors, and anti-CD38 antibodies. Nevertheless, in some patients, the disease continues to progress. For patients who have failed all three classes of drugs, the median progression-free survival is about 3 to 4 months, with a median overall survival of 8 to 9 months.

Product Is Awaiting Approval

Ide-cel is currently awaiting FDA approval, with a decision date slated for March 27.

Several CAR T-cell products are already marketed for use in certain leukemias and lymphomas, and there is another for use in multiple myeloma, ciltacabtagene autoleucel (cilta-cel, under development by Janssen), that is awaiting approval in Europe.

Strong and Sustained Responses

The trial involved 128 patients treated with ide-cel infusions. At the time of data cutoff for this report (January 14, 2020), 62 patients remained in the primary study. Of the 128 treated patients, the median age was 61 years and the median time since diagnosis was 6 years. About half (51%) had a high tumor burden (≥50% bone marrow plasma cells), 39% had extramedullary disease, 16% had stage III disease, and 35% had a high-risk cytogenetic abnormality, defined as del(17p), t(4;14), or t(14;16).

Patients in the cohort had received a median of six previous antimyeloma regimens (range, 3 to 16), and most of the patients (120, 94%) had undergone autologous hematopoietic stem cell transplants. In addition, the majority of patients (84%) had disease that was triple refractory (to an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody), 60% had disease that was penta-exposed (to bortezomib, carfilzomib, lenalidomide, pomalidomide, and daratumumab), and 26% had disease that was penta-refractory.

At a median follow-up of 13.3 months, 94 of 128 patients (73%) showed a response to therapy (P < .001), with 42 (33%) showing a complete or stringent complete response, and 67 patients (52%) showing a "very good partial response or better."

Overall median progression-free survival was 8.8 months at the 450×106 dose, but more than double that (20.2 months) for patients who achieved a complete or stringent complete response. Estimated median overall survival was 19.4 months, with an overall survival of 78% at 12 months. The authors noted that overall survival data are not yet mature.

After experiencing disease progression, 28 patients were retreated with ide-cel, with 6 patients showing a second response. The durations of response ranged from 1.9 to 6.8 months.

All patients in the cohort experienced adverse events, primarily grade 3 or 4 events that occurred in 127 patients (99%). The most common events reported were hematologic toxicities, including neutropenia in 114 patients (89%), anemia in 77 (60%), and thrombocytopenia in 67 (52%), and were at least partially related to the lymphodepleting chemotherapy administered before ide-cel infusion, the authors note. Cytokine release syndrome occurred in 107 patients (84%), primarily grade 1 or 2.

"Results of the KarMMa study support substantial antitumor activity for ide-cel across a target dose range of 150×106 to 450×106 CAR+ T cells," the authors conclude. "The 450×106 dose appeared to be somewhat more effective than the other doses."

New Option?

"What this study further highlights is that higher cell dose tends to increase cell expansion, which correlates to improved response and duration of response," commented Patel.

Importantly, multiple vulnerable subgroups experienced impressive outcomes, such as those who are older or with high risk or extramedullary disease, she noted.

"My patients who have undergone this therapy, albeit on other clinical trials, all say that their quality of life during this time of remission is priceless," Patel added. "The is the first therapy in the relapsed refractory setting that allows patients to have a significant chemo-free period. We need to find more ways to do this for our patients."

The study was supported by Bluebird Bio and Bristol-Myers Squibb. Pa tel has served on the advisory board for Janssen and Bristol-Myers Squibb. She also reports a speaking engagement with Oncopeptides. Munshi acts as a consultant for several pharmaceutical companies, and many co-authors also have relationships with industry, as listed in the original article.

N Engl J Med. Published online February 25, 2021. Abstract

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