Abecma cleared in EU as earlier therapy for hard-to-treat myeloma
Decision makes CAR T-cell therapy first OK'd in EU as earlier treatment
The European Commission has approved Bristol Myers Squibb (BMS)’s request to expand the use of the CAR T-cell therapy Abecma (idecabtagene vicleucel) as an earlier line of therapy for adults with multiple myeloma that’s difficult to treat.
The therapy was already approved in the European Union (EU) for people with relapsed or refractory myeloma (RRMM) who’d received three prior lines of therapy. All patients would have been triple-class exposed, meaning they’d have received the most common standard treatment classes: immunomodulators, proteasome inhibitors, and CD38 inhibitors.
With the new approval, the treatment can be used by triple-class exposed RRMM patients given at least two prior lines of therapy if the disease progressed after the most recent one.
The decision makes Abecma the first CAR T-cell therapy in the EU approved as an earlier line of treatment. The company said it’s working to make Abecma available to patients, including completing reimbursement agreements.
“Today’s approval in the European Union marks an exciting milestone in our efforts to bring the transformative potential of cell therapies into earlier lines of treatment,” Monica Shaw, MD, senior vice president and head of European markets for Bristol Myers Squibb, said in a company press release. “Abecma is an important treatment option for patients with triple-class exposed relapsed and refractory multiple myeloma who have received at least two prior therapies and is leading the way toward a promising shift in the treatment paradigm.”
Similar label expansions have been cleared in Japan and Switzerland, and one is under review in the U.S., where the therapy is approved for adults with triple-class exposed RRMM after four or more prior lines of therapy.
A U.S. Food and Drug Administration (FDA) advisory committee recently voted 8-3 in favor of Abecma demonstrating a favorable benefit/risk profile for triple-class exposed RRMM patients, which will be considered by regulators when they make their final decision. The agency hasn’t announced when a decision can be expected.
How does Abecma CAR T-cell therapy work for RRMM?
In multiple myeloma, immunomodulators, proteasome inhibitors, and CD38 inhibitors are increasingly being used in combination regimens as a single line of treatment, meaning more patients become triple-class exposed earlier in their treatment journey.
“As patients with multiple myeloma become exposed to the three main classes of therapy earlier in treatment and still experience relapsed and/or refractory disease, it is critical that we continue to add innovative treatment options to our arsenal that can potentially provide long-term disease control,” said Paula Rodriguez-Otero, MD, PhD, of the Clinica Universidad de Navarra, Spain.
CAR T-cell therapies like Abecma equip the immune system to better target cancer cells. To produce Abecma, a person’s immune T-cells are collected and lab-engineered to recognize a protein on myeloma cells called B-cell maturation antigen, or BCMA. The T-cells are then returned to patients via an infusion into the bloodstream, where they will find BCMA and bind to it, launching an attack against the myeloma cell that carries it.
Results from KarMMa-3 study prompted EU decision
A European Medicines Agency committee voted in favor of the label expansion this year based on data from the Phase 3 KarMMa-3 clinical trial (NCT03651128), which enrolled 386 triple-class exposed adults with RRMM who’d used two to four prior lines of therapy. The participants were randomly assigned to either Abecma or one of five standard myeloma treatment regimens.
After a median of around 2.5 years, Abecma had reduced the risk of disease progression or death by a little over half compared with the other regimens. The median survival time without cancer progression on Abecma was more than a year (13.8 months), a significant difference from a median of 4.4 months on standard regimens.
Nearly three-quarters of those on Abecma (71%) were considered treatment responders, with 44% achieving a complete or stringent complete response or better, meaning no cancer was detectable. This response was seen in less than half (41%) of those on standard regimens, with around 5% seeing no detectable cancer.
Also, 56% of those receiving standard regimens subsequently chose to receive Abecma when their disease progression was confirmed. This led to an increased median overall survival for the standard treatment group relative to what has been reported for this patient population (37.9 vs. about 13 months), the company said. Those originally assigned to Abecma had a median overall survival of 41.4 months.
Pooled analyses from clinical trials have shown that, while most Abecma-treated patients have cytokine release syndrome, a sudden type of immune response that’s common with CAR T-cell therapies, most weren’t severe. Neurotoxicity events occurred in about 16% of Abecma-treated patients, with 3% having severe or life-threatening events.
“This expanded approval of [Abecma] represents key progress in bringing a personalized therapy that delivers significantly improved, durable outcomes to patients with triple-class exposed relapsed and refractory multiple myeloma after two prior therapies,” Rodriguez-Otero said.
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