[Mike F]

Results of another new CAR T-cell Phase 1 trial

by Mike F on Thu May 31, 2018 4:02 pm

Just came across an article describing results of a Phase 1 trial of anti-BCMA CAR T-cell therapy for myeloma and thought I'd put it up here. This is not the same trial as the bb2121 trial that will have results discussed at the ASCO meeting. This one sounds very promising in terms of results, although the toxicity associated with it seems worse than what's mentioned in the bb2121 abstract. Note the median of 9.5 prior treatments for this small group of patients.

Source is as follows:

Brudno, et. al. T Cells Genetically Modified to Express an Anti-B-Cell Maturation Antigen Chimeric Antigen Receptor Cause Remissions of Poor-Prognosis Relapsed Multiple Myeloma., J Clin Oncol. 2018 May 29:, [Epub ahead of print] (abstract)

Here's the abstract::

Purpose - Therapies with novel mechanisms of action are needed for multiple myeloma. T cells can be genetically modified to express chimeric antigen receptors (CARs), which are artificial proteins that target T cells to antigens. B-cell maturation antigen (BCMA) is expressed by normal and malignant plasma cells but not normal essential cells. We conducted the first-in-humans clinical trial, to our knowledge, of T cells expressing a CAR targeting BCMA (CAR-BCMA).

Patients and Methods - Sixteen patients received 9 × 106 CAR-BCMA T cells/kg at the highest dose level of the trial; we are reporting results of these 16 patients. The patients had a median of 9.5 prior lines of multiple myeloma therapy. Sixty-three per­cent of patients had multiple myeloma refractory to the last treatment regi­men before protocol enroll­ment. T cells were transduced with a γ-retroviral vector encoding CAR-BCMA. Patients received CAR-BCMA T cells after a con­ditioning chemo­therapy regimen of cyclo­phos­phamide and fludara­bine.

Results - The overall response rate was 81%, with 63% very good partial response or complete response. Median event-free survival was 31 weeks. Responses included eradication of extensive bone marrow myeloma and resolution of soft-tissue plasma­cytomas. All 11 patients who obtained an anti-multiple myeloma response of partial response or better and had multiple myeloma evaluable for minimal residual disease obtained bone marrow minimal residual disease-negative status. High peak blood CAR+ cell levels were associated with anti-multiple myeloma responses. Cytokine-release syndrome toxicities were severe in some cases but were reversible. Blood CAR-BCMA T cells were pre­domi­nantly highly differ­entiated CD8+ T cells 6 to 9 days after infusion. BCMA antigen loss from multiple myeloma was observed.

Conclusion - CAR-BCMA T cells had substantial activity against heavily treated relapsed/ refractory multiple myeloma. Our results should encourage additional develop­ment of CAR T-cell thera­pies for multiple myeloma.