Japan OKs Abecma as 1st CAR T-cell for Heavily Treated Myeloma
Japan’s Ministry of Health, Labour, and Welfare has approved Abecma (idecabtagene vicleucel) as its first CAR T-cell therapy for adults with relapsed or refractory multiple myeloma who received at least three prior therapies.
This includes patients treated at least with one immunomodulatory drug (IMiD), one proteasome inhibitor (PI), and one CD38 inhibitor, and whose disease failed to respond or relapsed after their last therapy. In Japan, no other treatment is approved for this group of patients.
“Abecma delivers a new treatment option for patients with multiple myeloma, the first option directed against BCMA [B-cell maturation antigen] and using a new mode of action,” Jean-Christophe Barland, the president and CEO of Bristol-Myers Squibb (BMS) Japan, said in a press release. BMS is the developer of Abecma.
“This approval is a testament to our strong commitment to addressing unmet medical needs for patients in Japan,” Barland added.
Tadao Ishida, MD, PhD, of the Japanese Red Cross Medical Center, who participated in Abecma trials, said: “We hope that this cell therapy will bring new hope to patients suffering from relapsed or refractory multiple myeloma.”
“We will work diligently to develop a robust treatment system incorporating the proper use of Abecma so that we can contribute to the treatment of as many patients with multiple myeloma as possible,” Ishida added.
The approval follows a similar decision in Europe, as well as in the U.S., where the therapy is available for myeloma patients who have received at least four prior therapies.
In the U.S., Abecma is being jointly developed and commercialized by BMS and Bluebird Bio, while BMS holds exclusive manufacturing and commercialization rights outside the U.S.
Formerly known as ide-cel and bb2121, Abecma is a type of immunotherapy that uses a person’s own modified T-cells — a type of immune cell — to fight cancer.
It involves collecting T-cells from a patient and genetically modifying them in the lab to produce a human-made chimeric antigen receptor, or CAR, that helps them recognize the BCMA protein that is found at particularly high levels on the surface of myeloma cells. The engineered cells are then expanded and infused back into the patient.
By recognizing BCMA, these T-cells are expected to promote the death of myeloma cells, while leaving healthy cells largely unharmed.
Abecma’s approvals were based on data from the international, open-label KarMMa Phase 2 clinical trial (NCT03361748) and the CRB-401 Phase 1 clinical trial (NCT02658929), conducted in the U.S.
KarMMa, which took place in the U.S., Canada, Europe, and Japan, evaluated Abecma’s two-year safety and effectiveness in 149 myeloma patients who received at least three prior treatment regimens and failed to respond to their last one.
Top-line data showed that at a median follow-up of 11.3 months, 73.4% of the 128 patients who received the target dose (150–450 million CAR T-cells) responded to treatment, including 31.3% who achieved complete responses, meaning no signs of cancer.
Of the nine Japanese participants treated with the target dose, 88.9% responded to the therapy.
Treatment responses lasted for a median of 10.6 months, and patients lived without signs of disease progression for a median of 8.6 months.
The therapy’s safety profile was consistent with that reported in the prior CRB-401 trial, with the most common adverse events being low blood-cell counts and cytokine release syndrome (CRS).
CRS, a serious immune reaction that can be triggered by certain types of cancer immunotherapy, including CAR T-cell therapy, was severe, life-threatening, or fatal in 5.5% of patients.
The CAR T-cell therapy is also being investigated as an earlier line of treatment in the KarMMa-2 Phase 2 (NCT03601078) and KarMMa-3 Phase 3 (NCT03651128) trials, as well as a first-line therapy in the KarMMa-4 Phase 1 study (NCT04196491).
Abecma’s approval in Japan marks BMS’s second CAR T-cell therapy available in the country, the first being Breyanzi (lisocabtagene maraleucel) for adults with hard-to-treat large B-cell lymphoma, another type of blood cancer.
“I am very pleased that we have received approval for our second CAR T cell therapy, thus becoming the first and only company in Japan to receive approval for two CAR T cell therapies with distinct targets across multiple diseases,” Barland said.
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