Trial to Test Abecma in Patients With Poor Stem Cell Transplant Response
The CAR T-cell therapy extended survival in adults who didn't respond to other efforts: top-line data
An upcoming clinical trial will evaluate the CAR T-cell therapy Abecma (idecabtagene vicleucel) in people newly diagnosed with multiple myeloma who had a suboptimal response to a standard stem cell transplant.
Additional information about the KarMMa-9 trial, including its design and timing, will come at the earliest opportunity, according to 2seventy bio, which spun out of bluebird bio and is developing and commercializing Abecma in the U.S. in collaboration with Bristol Myers Squibb.
“Our focus at 2seventy is giving as much time as possible to patients who are battling cancer,” Steve Bernstein, MD, chief medical officer at 2seventy bio, said in a company press release.
“We are moving rapidly to expand our clinical study program to determine utility of Abecma in newly diagnosed multiple myeloma patients with suboptimal response to transplant. This population currently makes up more than half of multiple myeloma patients receiving transplant,” Bernstein said.
The announcement comes on the heels of top-line data from the KarMMa-3 Phase 3 trial (NCT03651128) that showed Abecma significantly extended progression-free survival in adults with multiple myeloma who had received two to four prior therapies and failed to respond to the last one.
The ongoing KarMMa-3 and the upcoming KarMMa-9 are two of the five KarMMa studies to follow the pivotal KarMMa Phase 2 trial (NCT03361748).
This study supported Abecma’s approval in the U.S., Europe, and Japan for treating adults with relapsed or refractory multiple myeloma who received at least three or four prior therapies. These include an immunomodulatory drug, a proteasome inhibitor, and a CD38 inhibitor.
“Given the efficacy data from our collective KarMMa studies and well-established and predictable safety profile seen in studies replicated in the real world, we believe there is tremendous potential for Abecma to help some of these patients earlier in their treatment path,” Bernstein said.
CAR T-cell therapy and ‘unmet need’
Autologous hematopoietic stem cell transplant is a standard treatment for eligible myeloma patients. It involves collecting a patient’s own healthy blood stem cells, eliminating all blood cells, and transplanting the stem cells back so their body can create new and healthy blood cells.
“Given the performance over other treatment options, autologous stem cell transplant will most likely continue to be the standard of care in patients newly diagnosed with multiple myeloma who are eligible,” Nikhil Munshi, MD, the director of basic and correlative science at the Dana-Farber Cancer Institute’s Jerome Lipper Multiple Myeloma Center, said.
However, some patients still fail to respond adequately to this approach, highlighting a high unmet need.
“The investigation of a well-established CAR T cell therapy, such as Abecma, in the newly diagnosed multiple myeloma treatment paradigm will be an important next step,” added Munshi, who is also Kraft family chair and a senior physician at Dana-Farber and a professor of medicine at Harvard Medical School.
CAR T-cell therapy is a type of immunotherapy wherein a patient’s own immune T-cells are isolated and engineered in the lab to produce a receptor protein called chimeric antigen receptor (CAR) that helps recognize and eliminate cancer cells. The engineered cells are then expanded and infused back into the patient.
In Abecma, previously known as ide-cel or bb2121, the engineered T-cells’ CAR is specifically designed to recognize BCMA, a protein found at high levels on myeloma cells. These T-cells are expected to kill off only myeloma cells, while leaving healthy cells largely unharmed.
KarMMa trial data
The pivotal KarMMa trial, which took place in the U.S., Canada, Europe, and Japan, assessed Abecma’s two-year safety and effectiveness in 149 myeloma patients who received at least three previous treatment regimens and failed to respond to their last one.
Top-line data showed 73.4% of the 128 participants who received the target dose of 150–450 million CAR T-cells responded to treatment, including 31.3% who showed no signs of cancer.
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.
Information from the largest dataset to date of Abecma’s real-world use were also consistent with KarMMa’s safety and efficacy findings. This despite 77% of patients having simultaneous health conditions that would have made them ineligible for that trial, 2seventy bio noted in its release.
Abecma is also being tested as an earlier line of treatment in the KarMMa-2 Phase 2 trial (NCT03601078) and the KarMMa-3 study, as well as a first-line therapy in the KarMMa-4 Phase 1 study (NCT04196491).
The Phase 1/2 KarMMa-7 trial (NCT04855136) is investigating the safety and effectiveness of Abecma in combination with other therapies.
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