key papersKey paper

Development and manufacture of novel locally produced anti-BCMA CAR T cells for the treatment of relapsed/refractory multiple myeloma: results from a phase I clinical trial (HBI0101)

A hospital in Jerusalem built and made its own CAR-T cells against the myeloma protein BCMA; in the first 20 heavily treated patients, 75 percent responded and half went into complete remission, with only mild immune reactions.

Report of the Hadassah phase 1 dose-escalation study (NCT04720313) of HBI0101, a second-generation optimised anti-BCMA CAR-T therapy developed in an academic setting and given fresh without cryopreservation. Twenty heavily pretreated patients with relapsed or refractory multiple myeloma were treated in three cohorts: 150 million (n = 6), 450 million (n = 7) and 800 million (n = 7) CAR-T cells.

Grade 1 or 2 cytokine release syndrome occurred in 18 patients (90 percent); no grade 3 or 4 cytokine release syndrome, no neurotoxicity of any grade and no dose-limiting toxicity were observed. The overall response rate was 75 percent, (stringent) complete response 50 percent and very good partial response 25 percent; responses were dose dependent, with 85 percent overall response, 71 percent complete response and 57 percent minimal residual disease negativity in the high-dose cohort. Median overall survival was 308 days (range 25 to more than 466), with estimated survival of 55 percent at the data cutoff; median progression-free survival was 160 days, with six patients progression free at the cutoff. The authors argue that the results support decentralised CAR-T production in academic centres to meet local demand.

Observational studyHas not changed practice yet20 participants

Authors

Asherie N, Kfir-Erenfeld S, Avni B, et al.

Published

Haematologica, 2023

Full text

doi:10.3324/haematol.2022.281628 PubMed 36200421

Findings

Overall response rate 75 percent, (stringent) complete response 50 percent and very good partial response 25 percent in 20 patients.
Grade 1 to 2 cytokine release syndrome in 90 percent; no grade 3 to 4 cytokine release syndrome, neurotoxicity or dose-limiting toxicity.
Dose-dependent responses: 85 percent response, 71 percent complete response and 57 percent MRD negativity at 800 million cells; median progression-free survival 160 days.

What it means

The clinical result is in line with commercial BCMA CAR-T products, but the point of the paper is the manufacturing: an academic hospital produced its own CAR-T cells, infused them fresh and treated patients who would otherwise wait for a commercial slot. It is the evidence base for what Immix Biopharma now develops as NXC-201.

Caveats

Phase 1 in 20 patients at a single centre; follow-up was short and the median progression-free survival of about five months is modest.
No comparison group; the historical comparators are the pivotal trials of idecabtagene vicleucel and ciltacabtagene autoleucel.
The registry lists a much larger continuing enrolment, so later cohorts are not described here.