ONCAlert | 2018 Gastrointestinal Cancers Symposium

Early Results Show High Response Rate Achieved With BCMA CAR T-cell Therapy in Multiple Myeloma

Jason Harris
Published Online: 2:27 PM, Tue June 6, 2017
Treatment with chimeric antigen receptor (CAR) T cells that target B-cell maturation protein (BMCA) achieved clinical remissions in 33 out of 35 patients (94%) with relapsed or refractory multiple myeloma in early results from a Chinese study presented at the 2017 ASCO Annual Meeting.

In findings from an ongoing phase I clinical trial, Wanhong Zhao, MD, PhD, an associate director of hematology at The Second Affiliated Hospital of Xi’an Jiaotong University in Xi’an, China, said patients achieved clinical remission (complete response, very good partial response, or partial response) within 2 months of infusion with CAR T-designated LCAR-B38M CAR T cells.

Of the 19 patients who have been followed for a minimum of 4 months, 14 have reached stringent complete response criteria, 1 patient has experienced partial response, and 4 others have achieved very good partial remission.

“LCAR-B38M CAR T technology exerts quick and reproducible therapeutic effects in refractory and relapsed multiple myeloma patients,” Zhao said. “More than 12 months’ follow-up of early patients shows durable and stringent complete remission, which raises hopes of cure.”

CAR T-cell therapy involves collecting a patient’s T cells, genetically reprogramming them in a lab, and then injecting them back into the patient, where they are designed to find and destroy cancer cells.

This is one of the first clinical trials of CAR T cells targeting BCMA, which was discovered to play a role in progression of multiple myeloma in 2004. Data from previous trials has shown CAR T-cell therapy targeting the protein CD19 to have efficacy in acute lymphoblastic leukemia (ALL) and some types of lymphoma, but there has been little success with CAR T-cell therapies targeting other biomarkers in other types of cancer.

Patients were infused with a median 4.7 (0.6 ~ 7.0) × 10e6/kg of LCAR-B38M CAR-T cells, split into three doses over a week. Zhao said the treatment began showing efficacy as early as 10 days after initial injection of CAR T cells. Overall objective response rate was 100% and 33 (94%) patients had an evident clinical remission of myeloma within two months of infusion.

None of the patients who achieved stringent complete response have experienced relapse. Five patients have been followed for 12 to 14 months, and all 5 remain in stringent complete response status and are free of minimal residual disease. Researchers observed a single incidence of disease progression from very good partial remission—an extramedullary lesion that reappeared 3 months after disappearing on CT scans.

Zhao said the data shows that LCAR-B38M technology also has an encouraging safety profile.

Most patients (85%) experienced cytokine release syndrome (CRS), a common and potentially dangerous side effect of CAR T-cell therapy, but the condition was generally transient and symptoms were described as “mild and manageable.” CRS symptoms can include fever, low blood pressure, and difficulty breathing, hypotension, and tachycardia.

Only 2 patients (5.7%) experienced a grade ≥3 CRS, both grade 3. Both patients recovered after treatment with an anti-inflammatory. No patients experienced neurologic side effects, another common and serious complication from CAR T-cell therapy.

Based on these results, researchers plan to enroll a total of 100 patients in the trial in China, and plan to conduct a similar trial in the U.S. in 2018. Eventually, they hope to determine if BCMA CAR T-cell therapy can benefit patients with newly diagnosed multiple myeloma.

“Although recent advances in chemotherapy have prolonged life expectancy in multiple myeloma, this cancer remains incurable,” said Zhao. “It appears that, with this novel immunotherapy, there may be a chance for cure in multiple myeloma, but we will need to follow patients much longer to confirm that.

Muhamed Baljevic, MD, assistant professor of medicine in the division of hematology and oncology at the University of Nebraska Medical Center, told Targeted Oncology that the response rates in this trial are “fabulous,” but because of the small population size and relatively short follow-up, there are still questions that must be answered before BMCA CAR T-cell therapy can be discussed as a cure.

“I’m very much encouraged by the fact that these results are seen in a trial involving BCMA as a target for CAR T cells. Probably the most critical factor for any CAR T cell therapy is the choice of antigen for targeting,” he said. “So far in multiple myeloma CAR T-cell development, we’ve had a couple of efforts that focused on anti-CD19 CAR T cells—successfully targeted in the ALL malignancy, as well—and anti-Kappa light chains, but I believe that BCMA is probably the better of those antigens to serve as a target for CAR T cell therapy because it is expressed most uniformly on myeloma cells, not normal cells.” 

“Multiple myeloma is considered an incurable disease, so of course [these results] show tremendous promise. In the scope of the timeline, we’re going to need much longer follow-up and demonstration of durable and sustained remissions before we can start talking about possible cures, [but] these are phenomenal response rates.” 
Fan X, Zhao W, Liu J, et al. Durable remissions with BCMA specific chimeric antigen receptor (CAR)-modified T cells in patients with refractory/relapsed multiple myeloma. J Clin Oncol. 35;2017 (suppl; abstr LBA3001).

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