Chimeric Antigen Receptor Therapies Continue to Do Well Against Blood Cancers

Chimeric antigen receptor approaches to cancer treatment involve taking a patient's T cells and equipping them with a new receptor that allows the immune cells to target specific characteristics of cancer cells. Despite the usual complications and challenges that tend to occur in the development of immunotherapies, involving potentially dangerous disruption of the immune system, this type of therapy has proven to be highly effective against blood cancers. It remains to be deployed against solid cancers, although researchers are well on their way towards reaching that goal, but there is every reason to expect it to be just as effective in that scenario.

In an early clinical trial, 33 out of 35 (94%) patients had clinical remission of multiple myeloma upon receiving a new type of immunotherapy - chimeric antigen receptor (CAR) T cells targeting B-cell maturation protein or BCMA. Most patients had only mild side effects. "Although recent advances in chemotherapy have prolonged life expectancy in multiple myeloma, this cancer remains incurable. 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 (ALL) 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 progression of multiple myeloma in 2004.

The authors report results from the first 35 patients with relapsed or treatment-resistant (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 (94%) patients had an evident clinical remission of myeloma (complete response or very good partial response) within two months of receiving CAR T cells. To date, 19 patients have been followed for more than four months, a pre-set time for full efficacy assessment by the International Myeloma Working Group (IMWG) consensus. Of the 19 patients, 14 have reached stringent complete response (sCR) criteria, one patient has reached partial response, and four patients have achieved very good partial remission (VgPR) criteria in efficacy. There has been only a single case of disease progression from VgPR; an extramedullary lesion of the VgPR patient reappeared three months after disappearing on CT scans. There has not been a single case of relapse among patients who reached sCR criteria. The five patients who have been followed for over a year (12-14 months) all remain in sCR status and are free of minimal residual disease as well (have no detectable cancer cells in the bone marrow).

Cytokine release syndrome or CRS, a common and potentially dangerous side effect of CAR T-cell therapy, occurred in 85% of patients, but it was only transient. In the majority of patients symptoms were mild and manageable. CRS 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 CRS (grade 3) but recovered upon receiving tocilizumab, an inflammation-reducing treatment commonly used to manage CRS in clinical trials of CAR T-cell therapy. No patients experienced neurologic side effects, another common and serious complication from CAR T-cell therapy.

Link: http://www.asco.org/about-asco/press-center/news-releases/car-t-cell-therapy-sends-multiple-myeloma-lasting-remission

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