Novel CAR-T Drug Promising in Relapsed or Refractory MM

A new stem cell memory chimeric antigen receptor (CAR) T-cell therapy, P-BCMA-101, has demonstrated exceptional efficacy and safety in patients with relapsed and/or refractory multiple myeloma, according to a recent press statement by the manufacturer behind the drug, Poseida Therapeutics  (September 5, 2018).

These results come from an update based on 11 patients currently enrolled in an ongoing safety and efficacy trial of P-BCMA-101.

Phase 1 Clinical Trial of P-BCMA-101

The primary end point of this ongoing, open-label, multicenter clinical trial —which plans to enroll a maximum of 40 patients with relapsed and/or refractory multiple myeloma—is to determine the safety and maximum-tolerated dose of P-BCMA-101. The secondary end points include the anti-myeloma effects of the drug.

As of August 10, 2018, 11 patients had received treatment across 3 dosage groups with average CAR T-cell doses of 51 × 106 (n = 3), 152 × 106 (n = 7), and 430 × 106 (n = 1). The patients were heavily pretreated with a median of 6 previous therapy lines, and had a median age of 60 years. Among these patients, 73% were considered high-risk, including those with high-risk cytogenetics.

Promising Preliminary Results

Between days 14 and 21, investigators observed a peak T-cell expansion that they deemed more gradual than the peak expansion generally seen with other CAR-T therapies (ie, 5-14 days). This gradual peak expansion was associated with decreased acute cytokine release, and fewer other adverse events.

A single instance of suspected cytokine release syndrome in 1 patient was rapidly resolved without tocilizumab therapy or steroids. According to the investigators, biomarkers of cytokine release syndrome (eg, interleukin 6 levels) in these patients have lower peak levels than those seen in patients from other anti–B-cell maturation antigen CAR-T therapy trials.

Neutropenia and thrombocytopenia were the most frequently reported adverse events with P-BCMA-101. No dose-limiting toxicities occurred at any dose.

“The latest data results show that P-BCMA-101 induces deep responses in a heavily pretreated population with relapsed/refractory multiple myeloma, with some patients reaching VGPR [very good partial response] and even stringent CR [complete response] at early efficacy assessments,” said Eric Ostertag, MD, PhD, Chief Executive Officer, Poseida Therapeutics, in the press release.

“We are…encouraged that P-BCMA-101 is demonstrating significant efficacy even at doses that have been ineffective for other anti-BCMA CAR-T therapies and that our response rates continue to improve as the dose increases,” he added. —Janelle Bradley