Conference Coverage

CT103A elicits responses after prior CAR T-cell relapse



BOSTON – CT103A, a chimeric antigen receptor (CAR) T-cell therapy, is “active and effective” in patients with relapsed/refractory multiple myeloma, according to a speaker at the International Myeloma Workshop, held by the International Myeloma Society.

Chunrui Li, MD, PhD, of Tongji Hospital of Tongji Medical College, Huazhong University of Science, Wuhan, Hubei, China Jennifer Smith/MDedge News

Dr. Chunrui Li

The anti–B-cell maturation antigen (BCMA) CAR T-cell therapy produced a 100% response rate in patients with heavily pretreated multiple myeloma, and three of four patients who had failed a prior CAR T-cell therapy achieved a stringent complete response after CT103A.

Chunrui Li, MD, PhD, of Tongji Hospital and Tongji Medical College, Huazhong University of Science, Wuhan, China, presented these results at the workshop.

Dr. Li noted that anti-BCMA CAR T-cell therapy has produced responses in myeloma patients, but approximately half of patients typically relapse in about a year. CAR T-cell infusions after relapse have not been effective in these patients.

In an effort to change that, Dr. Li and his colleagues developed CT103A, a lentiviral vector containing a CAR structure with a fully human single-chain fragment variant; CD8a hinger; and transmembrane, 4-1BB co-stimulatory, and CD3z activation domains.

Dr. Li and his colleagues evaluated CT103A in a phase 0 trial (ChiCTR1800018137) of 18 patients who had received at least three prior lines of therapy and had disease refractory to a proteasome inhibitor and an immunomodulatory agent.

The patients’ median age was 53.3 years (range, 38-66 years), and their median time since diagnosis was 32 months (range, 8-92 months). They had received a median of 4 (range, 3-6) prior therapies. All had received prior bortezomib and lenalidomide, seven had undergone a transplant, and four had been treated on a trial of murine anti-BCMA CAR T-cell therapy.

For the current trial, patients received lymphodepletion with cyclophosphamide and fludarabine, followed by CT103A at 1x106, 3x106, or 6x106 CAR T cells/kg.

There was one dose-limiting toxicity at the highest dose level – grade 4 cytokine release syndrome (CRS) in a patient who died at day 19 after CT103A infusion.

In all, 17 patients developed CRS, four with grade 1, eight with grade 2, four with grade 3, and one with grade 4 CRS. None of the patients developed neurologic toxicity.

Serious adverse events related to lymphodepletion and/or CT103A included prolonged cytopenia (n = 3), pulmonary infection (n = 2), herpes zoster (n = 1), pleuritis (n = 1), and hypoxemia (n = 1).

There were 17 patients evaluable for efficacy, and all of them achieved a response at some point. In eight patients, responses have lasted more than 200 days.

At the data cutoff, there were 10 stringent complete responses, two complete responses, and three very good partial responses. One patient progressed after achieving a very good partial response, and one patient achieved a partial response but ultimately died (likely of respiratory failure attributable to a lung infection).

Of the four patients who had previously received murine CAR T-cell therapy, one progressed, and three achieved a stringent complete response.

This study was funded by Nanjing Iaso Biotherapeutics. Dr. Li did not disclose any conflicts of interest.

SOURCE: Li C et al. IMW 2019, Abstract OAB-033.

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