MCARH171, a BCMA-Targeted CAR-T in Relapsed/Refractory Multiple Myeloma: Phase 1 Readout

The following article features coverage from the American Society of Hematology (ASH) 2018 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

There was much excitement (and numerous audience questions) swirling about the readout of the results from a phase 1 trial featuring MCARH171, a human-derived BCMA-targeted CAR-T in patients with relapsed/refractory multiple myeloma. The findings were presented by Sham Mailankody, MBBS, of Memorial Sloan Kettering Cancer Center, New York, New York, at the 2018 American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego, California.¹

The focus was on the investigational agent’s expansion and persistence: the highest peak expansions seen in patients occurred at the dose of at least 450 × 10⁶ cells and at that dose, yielded responses including partial response, very good partial response (VGPR), and stable disease. Two patients had ongoing VGPRs at 10 months and 12 months.

A prerequisite of trial enrollment was that all patients had to be BCMA-positive by immunohistochemistry.

MCARH171 was determined to have an acceptable safety profile, with no dose-limiting toxicities reported. While there was no clear dose-response seen for toxicities such as cytokine release syndrome, there was a dose-response for efficacy, “with promising responses at dose levels of ≥ 450 × 10⁶ cells,” according to Dr Mailankody, who added that peak expansion correlated with durability of response. Ultimately, the team concluded the results from the study supported the development of human-derived BCMA-targeted CAR-T for myeloma.

There was a patient, patient 10, who demonstrated a slight decline in BCMA expression, but there were no patients who saw a loss of BCMA expression, Dr Mailankody emphasized during the presentation.

Many of the questions for Dr Mailankody following the presentation centered around the similarities and differences between MCARH171 and other CARs under investigation by Dr Mailankody’s team, such as JCARH125, which does not rely on measures of patient BCMA expression for clinical trial enrollment.

“Comparing 2 different strategies is fraught with hazards,” Dr Mailankody warned. “But, there are differences to the CAR T cells; the construct is slightly different, the antigen-recognizing [portion of the CAR] is slightly different for the 2 products. There are other differences; retroviral vs lentiviral, transduction, for instance … the manufacturing process is different. Either or both of those factors might contribute to potential differences in efficacy. That said, we do see 3 out of 5 patients who have VGPR at higher doses, 2 of them ongoing at 10 to 12 months [for] MCARH171 … just speaking of limitations to how many trials we can assign for the same target, we decided to focus on JCARH125, it certainly seems to have responses at lower doses, durability, and the other factors we already discussed.”

He added that the manufacturing for MCARH171 was “unselected manufacturing”; his team did not control for CD4 or CD8. When asked if he observed any correlation between the ratio of these and patient response, Dr Mailankody said, “small numbers … but when we looked at responses, there was no clear trend with dose and responses, or toxicities related to specific ratio of CD4 or CD8 in the product.”

Disclosure: This work is linked to a pharmaceutical company; please refer to the abstract for a full list of disclosures.

Disclosures: This study was supported by Poseida Therapeutics. Please refer to the original abstract for a complete list of authors’ disclosures.

Reference

1. Mailankody S, Ghosh A, Staehr M, et al. Clinical responses and pharmacokinetics of MCARH171, a human-derived Bcma targeted CAR T cell therapy in relapsed/refractory multiple myeloma: final results of a phase I clinical trial. Oral presentation at: American Society of Hematology 60th Annual Meeting & Exposition; December 1-4, 2018; San Diego, California. Abstract 959.