Abecma cuts worse outcomes risk in half in hard-to-treat myeloma cases
Findings show 'benefit' of CAR T-cell therapy over standard treatments
Abecma (idecabtagene vicleucel or ide-cel) reduced the risk of disease progression or death by half in adults with relapsed or refractory multiple myeloma (RRMM) who’d received two to four therapies without responding to the last one.
That’s according to full results of the Phase 3 KarMMa-3 clinical trial (NCT03651128), which also showed that Abecma — a CAR T-cell therapy — resulted in a significantly greater response rate than standard treatment regimens.
The findings, adding to previously reported interim data, were detailed in the study “Ide-cel or Standard Regimens in Relapsed and Refractory Multiple Myeloma,” published in the New England Journal of Medicine. The main results were also presented at the European Group for Blood and Marrow Transplantation and the European Hematology Association’s European CAR T-cell Meeting on Feb. 10.
“We are pleased to present and have these data published to build on the compelling efficacy profile of Abecma demonstrating significant improvement in progression-free survival,” said Steve Bernstein, MD, chief medical officer of 2seventy bio, which codeveloped the therapy with Bristol Myers Squibb (BMS), in a joint company press release.
“Results from the KarMMa-3 study with Abecma clearly demonstrate the benefit of earlier use of a CAR T-cell therapy in providing the longest progression-free survival for patients with relapsed and refractory multiple myeloma compared to current standard regimens for these patients,” said Paula Rodriguez-Otero, MD, PhD, the study’s first author at the hematology department of the University of Navarra Clinic.
Bernstein said the companies “look forward to working with regulatory authorities to make Abecma available to more myeloma patients who could benefit from this important treatment option.”
The therapy is approved in Europe and Japan for RRMM patients who’ve received at least three prior therapies, including one immunomodulatory drug, one proteasome inhibitor, and one CD38 inhibitor. In the U.S., it’s available for patients who’ve undergone at least four prior therapies.
As a CAR T-cell therapy, Abecma uses a person’s own immune system to target and kill cancer cells. Immune cells with anti-cancer abilities, called T-cells, are collected and genetically modified to target a specific protein, BCMA, found in high levels at the surface of myeloma cells.
The modified cells are multiplied and infused back into the patient in a single administration, and are expected to attack myeloma cells and generally leave healthy cells unharmed.
The international KarMMa-3 trial tested Abcema as an earlier line of therapy in 386 adults with RRMM who received two to four prior treatments — including an immunomodulatory agent, a proteasome inhibitor, and the CD38 inhibitor Darzalex (daratumumab) — and hadn’t responded to their last regimen.
Abecma vs. standard treatment
Participants were randomly assigned to receive either Abecma (254 patients) or one of five standard combination therapy regimens (132 patients). These regimens were maintained until disease progression was detected, toxic side effects occurred, or the patient withdrew from the trial.
Patients in both groups had a median age of 63 and about 60% were men and white. Two-thirds (66%) had triple-class-refractory disease, meaning they didn’t respond to immunomodulatory therapy, proteasome inhibitors, and Darzalex.
Results showed that over a median follow-up of 18.6 months, Abecma-treated patients lived three times longer without signs of disease progression than those in the standard regimen group (13.3 vs. 4.4 months). This corresponded to a 51% reduction in risk of disease progression or death with Abecma, meeting the trial’s main goal.
These findings were consistently observed when patients were divided into subgroups, including by age, race, number of previous therapies, and difficult-to-treat disease categories, such as having a high tumor burden or triple-class refractory disease.
Patients’ overall response rate was also significantly better in the Abecma group than the standard regimen group, achieving one of the study’s key secondary goals. Nearly three-quarters (71%) of patients treated with Abecma achieved a partial or better response versus 42% on standard regimens.
A greater proportion of Abecma-treated patients achieved a complete response or stringent complete response (no detectable cancer) relative to those on standard treatment (39% vs. 5%). Responses to Abecma were also more robust, with a median duration of 14.8 months versus the standard regimens’ 9.7 months.
“The KarMMa-3 study is the first with a BCMA-directed CAR T therapy to demonstrate superiority versus standard regimens for patients with relapsed and refractory multiple myeloma, illustrating the potential of Abecma to change the standard of care of triple-class exposed multiple myeloma [patients] in early lines,” Bernstein said.
Side effects of CAR T-cell therapy
Data on overall survival, another key secondary goal, were considered immature, meaning more follow-up time is needed before researchers can assess it properly.
The therapy’s safety profile was consistent with that reported in previous Abecma trials, with no new safety signals identified.
A greater proportion of Abecma-treated patients had severe or life-threatening side effects than in the standard regimen group (93% vs. 75%). The most common was low counts of blood cells and infection. Six (3%) Abecma patients and one (1%) standard regimen patients died of a side effect deemed related to treatment.
Occurrence of cytokine release syndrome (CRS), a serious immune reaction that can be triggered by CAR T-cell therapy, was restricted to the Abecma group and was most commonly of mild to moderate severity. However, nine patients (4%) had a severe or life-threatening CRS and in two (1%), the immune reaction led to death.
Neurological toxic effects were also restricted to the Abecma group, occurring in 15% of patients; 3% had a serious or life-threatening event.
These results show “the clear clinical benefit of using Abecma across lines of therapy for patients with triple-class exposed relapsed and refractory multiple myeloma to provide the best chance for lasting disease control,” said Anne Kerber, MD, BMS’ senior vice president and head of cell therapy development.
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