More than 2 years after treatment, some of the patients with relapsed/refractory multiple myeloma have yet to see a relapse. An FDA decision on the therapy is expected within a month.
A chimeric antigen receptor (CAR) T-cell therapy targeting B-cell maturation antigen (BCMA) in relapsed/refractory multiple myeloma led to a disappearance of the incurable cancer in 33% of patients, according to results published this week in The New England Journal of Medicine, just a few weeks before an expected decision by the FDA.
If idecabtagene vicleucel (ide-cel, also called bb2121), is approved, it would be the first CAR T-cell therapy available in multiple myeloma.
The phase 2 study, called KarMMa, enrolled 140 patients with active myeloma after receiving at least 3 previous therapies, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody.
Among the 128 treated patients, the median age was 61 years and the median time since diagnosis was 6 years. A total of 65 patients (51%) had a high tumor burden (≥50% bone marrow plasma cells), 50 (39%) had extramedullary disease, 21 (16%) had stage III disease at screening according to the revised International Staging System, and 45 (35%) had a high-risk cytogenetic abnormality, defined as del(17p), t(4;14), or t(14;16).
The primary end point was an overall response (partial response [PR] or better), and a secondary end point was a CR or better (comprising complete and stringent complete responses).
Patients received ide-cel target doses of 150×106 to 450×106 CAR-positive (CAR+) T cells.
Of the 140, 128 received ide-cel. A little more than one-third (33%) of the patients who received a single dose of ide-cel had a complete response (CR) to the therapy, and 75% responded.
At a median follow-up of 13.3 months, 73% of the patients had achieved PR or better.
Of the one-third who had a CR or better, the majority—79%—had no detectable disease as measured by minimal residual disease (MRD)–negative status (<10−5 nucleated cells), representing 26% of all 128 patients who were treated .
The median progression-free survival (PFS) was 8.8 months (95% CI, 5.6-11.6). Overall survival was 19.4 months, and the 450×106 dose produced numerically longer median response duration and PFS (11.3 months and 12.1 months, respectively).
Even today, more than 2 years after treatment, some of the patients have yet to see a relapse.
"Despite numerous advances in the treatment of multiple myeloma, relapses are common. Patients whose disease continues to worsen after receiving standard therapy have relatively few treatment options that provide high response rates," Nikhil Munshi, MD, of Dana-Farber Cancer Institute and trial leader, said in a statement. "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."
Anti-tumor activity was seen across all patient subgroups, the authors said.
The most common side effects were low blood-cell counts and cytokine release syndrome, which are common with CAR t-cell treatment.
In September 2020, the FDA accepted for Priority Review application for ide-cel from bluebird bio and Bristol Myers Squibb and set a Prescription Drug User Fee Act (PDUFA) date of March 27, 2021.
Munshi NC, Anderson LD, Shah N, et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N Engl J Med. 2021; 384:705-716