March 2016, Vol. 5, No. 2
First-in-Human CAR T-Cell Trial Shows Activity in Multiple MyelomaASH 2015, ASH Highlights
CAR T-cell therapy has been striking in various hematologic malignancies, and, for the first time, the approach is being evaluated in multiple myeloma.
At the meeting, James Kochenderfer, MD, of the Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, presented preliminary results from a phase 1 study in 12 patients. Patients had received a median of 7 prior lines of therapy.
â€śWe have demonstrated for the first time that CAR T cells can have powerful activity against measurable multiple myeloma,â€ť Kochenderfer said.
For myeloma, the target of the chimeric antigen receptor (CAR) therapy is the B-cell maturation antigen (BCMA). BCMA is expressed in 60% to 70% of myeloma patients.
The study evaluated 4 dose levels of CAR T-cell infusion, which patients received after 3 days of a chemotherapy regimen to enhance the activity of the CAR T cells.
Approach Most Effective at High Doses
â€śAnti-BCMA CAR T cells eliminated plasma cells, and importantly, did not cause direct damage to essential organs,â€ť Kochenderfer reported. â€śResponses included an ongoing stringent complete remission in a patient with a high burden of chemotherapy-resistant myeloma.â€ť
The investigators observed 1 stringent complete response (ongoing at more than 14 weeks), 1 very good partial response, 2 partial responses, and 8 cases of stable disease.
The best respondersâ€”the patients treated at the highest dosesâ€”also experienced the most toxicities, primarily severe cytokine release syndrome. Toxicity among the patients treated with the lowest 3 dose levels was mild and included cytopenias, fever, and signs of cytokine release syndrome.
For example, patient 10 had very chemotherapy-resistant disease, but his myeloma cells were â€śrapidly eliminatedâ€ť by CAR T-cell infusions.
â€śHe obtained an ongoing stringent complete remission of chemotherapy-resistant IgA myeloma after CAR-BCMA T-cell infusion,â€ť he reported. â€śMultiple myeloma that made up more than 90% of patient 10â€™s bone marrow cells was eliminated.â€ť The patient experienced cytokine release syndrome starting 4 hours after infusion, including fever, tachycardia, dyspnea, hypotension, and other complications, which resolved within 2 weeks.
Patient 11 al so experienced significant toxicity but had a dramatic reduction in myeloma. His M protein levels are continuing to decrease.
Kochenderfer said the toxicity as a whole was â€śsubstantial but reversibleâ€ť and similar to that seen on previous CAR T-cell trials.
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