ASCO 2017: BCMA-Specific CAR T-Cell Therapy Sends Relapsed/Refractory Multiple Myeloma Into Lasting Remission in an Early Trial

Key Points

  • Overall, the objective response rate was 100%, and 33 patients (94%) had an evident clinical remission of myeloma (complete response, very good partial response, or partial response) within 2 months of receiving CAR T cells.
  • After following the group for a period of more than 4 months, of the 19 patients, 14 have reached stringent complete response criteria, 1 patient has reached partial response, and 4 patients have achieved very good partial remission criteria in efficacy.
  • Cytokine-release syndrome, a common and potentially dangerous side effect of CAR T-cell therapy, occurred in 85% of patients, but it was transient. No patients experienced neurologic side effects, another common and serious complication of CAR T-cell therapy.

In an early clinical trial, 33 out of 35 (94%) patients had clinical remission of multiple myeloma upon receiving immunotherapy with chimeric antigen receptor (CAR) T cells targeting B-cell maturation protein, or BCMA. Most patients had only mild side effects. The study was presented by Fan et al today at the 2017 ASCO Annual Meeting (Abstract LBA3001).

“Although recent advances in chemotherapy have prolonged life expectancy in multiple myeloma, this cancer remains incurable,” said study author Wanhong Zhao, MD, PhD, an Associate Director of Hematology at The Second Affiliated Hospital of Xi’an Jiaotong University in Xi’an, China. “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.”

CAR T-cell therapy is custom-made for each patient. The patient’s own T cells are collected, genetically reprogrammed in a lab, and injected back into the patient. The reprogramming involves inserting an artificially designed gene into the T-cell genome, which helps the genetically reprogrammed cells find and destroy cancer cells throughout the body.

Over the past few years, CAR T-cell therapy targeting a B-cell biomarker called CD19 proved very effective in initial trials for acute lymphoblastic leukemia and some types of lymphoma, but until now, there has been little success with CAR T-cell therapies targeting other biomarkers in other types of cancer. This is one of the first clinical trials of CAR T cells targeting BCMA, which was discovered to play a role in the progression of multiple myeloma in 2004.

Key Findings

The authors reported results from the first 35 patients with relapsed or refractory multiple myeloma enrolled in this ongoing phase I clinical trial in China. First signs of treatment efficacy appeared as early as 10 days after initial injection of CAR T cells (patients received three split doses of cells over a week). Overall, the objective response rate was 100%, and 33 patients (94%) had an evident clinical remission of myeloma (complete response, very good partial response, or partial response) within 2 months of receiving CAR T cells.

To date, 19 patients have been followed for more than 4 months, a preset time for full efficacy assessment by the International Myeloma Working Group consensus. Of the 19 patients, 14 have reached stringent complete response criteria, 1 patient has reached partial response, and 4 patients have achieved very good partial remission criteria in efficacy.

There has been only a single case of disease progression after very good partial remission; an extramedullary lesion of this patient reappeared 3 months after disappearing on CT scans. There has not been a single case of relapse among patients who reached stringent complete response criteria. The 5 patients who have been followed for over 1 year (12 to 14 months) all remain in stringent complete response status and are free of minimal residual disease as well.

Cytokine-release syndrome, a common and potentially dangerous side effect of CAR T-cell therapy, occurred in 85% of patients, but it was transient. In the majority of patients, symptoms were mild and manageable. Cytokine-release syndrome is associated with symptoms such as fever, low blood pressure, difficulty breathing, and problems with multiple organs. Only two patients on this study experienced severe cytokine-release syndrome (grade 3), but they recovered upon receiving tocilizumab (Actemra), an inflammation-reducing agent. No patients experienced neurologic side effects, another common and serious complication from CAR T-cell therapy.

Next Steps

The researchers plan to enroll a total of 100 patients in this clinical trial at 4 participating hospitals in China. “In early 2018, we also plan to launch a similar clinical trial in the United States. Looking ahead, we would like to explore whether BCMA CAR T-cell therapy benefits patients who are newly diagnosed with multiple myeloma,” said Dr. Zhao.

Commentary

“While it’s still early, these data are a strong sign that CAR T-cell therapy can send multiple myeloma into remission. It’s rare to see such high response rates, especially for a hard-to-treat cancer. This serves as proof that immunotherapy and precision medicine research pays off. We hope that future research builds on this success in multiple myeloma and other cancers,” said ASCO Expert Michael S. Sabel, MD, FACS.

This study was funded by Legend Biotech Co.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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