Gene Therapy Shows Potential in Multiple Myeloma Trials


CAR T cell therapy resulted in a high response rate among previously-treated patients with multiple myeloma.

Novel immunotherapy approaches have demonstrated significant benefits in patients with drug-resistant multiple myeloma (MM) who experienced a relapse, according to abstracts presented at the Annual American Society of Hematology Meeting and Exposition.

In one of the studies, the authors investigated the efficacy of a CAR T cell treatment administered after chemotherapy, which elicited a response in 64% of patients. In another study, patients received an infusion of a monoclonal antibody, leading to a 60% response rate.

Both of the strategies acted on the B-Cell Maturation Antigen (BCMA) receptor, a treatment target for MM.

MM is a bone marrow malignancy in which plasma cells turn cancerous and cause bone tumors, anemia, kidney failures, and infections. Current estimates suggest that more than 30,200 patients will develop MM in 2017. Treatment strategy includes chemotherapy, radiation, and stem cell transplant in some cases.

In the first study, the authors examined CART-BCMA, which included reprogramming patients’ T cells to target cancer cells. Once the T cells were infused into the body, they proliferate and target BCMA-expressing cells, according to the authors.

Prior to the infusion, patients received a dose of chemotherapy to diminish white blood cells. Then, patients received 2 doses of CART-BCMA.

The authors found that of the 5 patients included in the lower dosage group, 40% achieved at least a minor response. Of the 10 patients in the higher dose group, 80% achieved a minor response or better and 1 patient in the higher dosage cohort achieved a complete response, according to the study.

However, 12 of the 15 patients developed cytokine-release syndrome, which is characterized by high fevers, nausea, muscle pain, and other flu-like symptoms, according to the study.

The trial is currently ongoing with more patients receiving higher dose CART-BCMA therapy, according to the authors. These patients were treated with the cytokine inhibitors tocilizumab and siltuximab.

Another 3 patients experienced neurotoxicity, which resolved without treatment, according the study.

“This follows up on our previous report that showed that six out of nine patients had clinical benefit to CART-BCMA given alone, without chemotherapy,” said lead author Adam D. Cohen, MD. “All of these data indicate BCMA is an attractive target in refractory myeloma, and our hope is that combining the CAR T cells with chemotherapy will increase the expansion and persistence of the CAR T cells, though longer follow-up is needed to assess this.”

In the second study, researchers targeted BCMA with GSK2857916, an experimental drug granted breakthrough therapy designation. The novel treatment links chemotherapy to a monoclonal antibody against BCMA, which targets drug delivery to MM cells.

Patients received an infusion every 3 weeks for up to 16 cycles. At baseline, 57% of patients had previously received 5 or more lines of chemotherapy.

The overall response rate was 60%, with 51% of patients achieving a very good partial response, according to the study. Median progression-free survival was approximately 8 months.

The authors noted that many patients experienced significant eye toxicity, but these adverse events were related to chemotherapy and resolved with lower dose treatment.

“Response rates that high are really unprecedented for a single agent in relapsed, refractory disease,” Dr Cohen said. “It’s especially important to this patient population, since they are heavily pre-treated and have limited options for treatment.”

Overall, these studies suggest that immunotherapy options may be effective for patients with MM.

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