A one-time infusion of an investigational CAR T-cell therapy that targets a protein found on most multiple myeloma cells elicited an 86-percent overall response rate in 21 patients whose disease had come back or had not responded after a median of seven prior treatments, according to results from a Phase I study.

This information was presented in a press conference at the 2017 ASH annual meeting. 

For more information watch our interview with Dr Kochenderfer.

Among 18 patients who received higher, active doses of infused CAR T cells, this response rate increased to 94 percent, with manageable adverse effects, researchers reported.

Among these 18 patients, 10 achieved a complete response and 9 of 10 evaluated for minimal residual disease (MRD) using sensitive genetic tests achieved an MRD-negative response.

After a median follow-up period of 40 weeks, the median progression-free survival had not been reached; four patients who received active doses had seen their disease get worse.

“We are excited about the early results in a patient population with very advanced myeloma for whom previous therapies have failed,” said senior study author James N. Kochenderfer, MD, of the Center for Cancer Research at the National Cancer Institute in Bethesda, Maryland.

These findings are important, Dr. Kochenderfer said, because despite recent therapeutic advances, multiple myeloma — a cancer that begins in plasma cells, cells in the bone marrow that help the body fight infection — remains nearly incurable.

Existing therapies require patients to stay on treatment long-term with drugs that have side effects, he said.

“CAR T-cell therapy is completely different from other available treatments for multiple myeloma,” Dr. Kochenderfer said.

“We have patients who have a sustained response and have been able to go for over a year with no additional myeloma therapy and tolerable adverse effects.”

The study, conducted at nine sites in the United States, is the first U.S.-based multicentre study of a CAR T-cell therapy engineered to target BCMA, a protein found on the vast majority of both myeloma tumour cells and normal plasma cells, but no other healthy tissues.

An estimated 30,000 people in the United States will be diagnosed with multiple myeloma in 2017.

Twenty-one patients with a median age of 58 years were enrolled in the dose-escalation phase of the study.

All had seen their disease come back or stop responding after a median of seven prior treatments, including a stem cell transplant.

The primary objective of the Phase I study was to identify the “maximum tolerated dose” of the experimental treatment — that is, the highest dose that could be given without unacceptable levels of adverse effects.

Additional outcome measures included evaluating whether any cancer cells remained in the bone marrow, the length of time until the cancer began to get worse, and response to treatment as measured by a standard set of criteria for assessing multiple myeloma.

Most patients experienced adverse effects, including low blood counts, CRS, and neurologic symptoms.

All three patients treated at an inactive CAR-T dose, the lowest dose in the dose-escalation stage of the trial, died from progression of their myeloma within one year.

Among the 18 patients treated at active CAR-T doses, two patients died from other causes while their myeloma was in a complete response to CAR-T therapy.

These findings are preliminary and, as a Phase I trial, the study had no control group and was designed primarily to identify a safe dose of bb2121, not to evaluate the drug’s effectiveness.

Source: ASH 2017