Early Findings Indicate P-BCMA-101 May Be Effective, Tolerable in R/R Multiple Myeloma
Early results of phase 1, dose-escalation trial demonstrate efficacy and safety of P-BCMA-101 CAR-T cell therapy in patients with R/R MM.
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Early results of an ongoing phase 1, dose-escalation trial studying the efficacy and safety of P-BCMA-101 chimeric antigen receptor (CAR)-T cells in patients with relapsed/refractory (R/R) multiple myeloma (MM) were presented by Tara Gregory, MD, of University of Texas MD Anderson Cancer Center in Houston, at the 2018 American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego, California.1
At this time, 23 patients have been treated in 5 dose groups. The median age of patients is 61 years (range, 42 to 74) and 70% were male. Fourteen patients had high-risk disease and the median number of prior regimens was 6 (range, 3 to 11).
The researchers found that 21 patients experienced treatment-emergent adverse events; however, no patients experience dose-limiting toxicities. Two patients experienced cytokine release syndrome (1 being grade 2 and 1 being grade 1; both with low peak IL-6). There were no other use of tocilizumab, steroids, cytotoxic agents, rimiducid (safety switch), or ICU admissions for either of these patients. Neutropenia was observed in 14 patients, 10 patients experienced thrombocytopenia, 8 patients experienced anemia, and 8 patients experienced infection (6 in the first month of treatment). There was also one case of potential CRES (grade 2), which was treated with toclilizumab and steroid.
Overall response rate was 50%, 71%, 42%, and 100% at the mean doses of 52×106, 152×106, 456×106, and 857×106, respectively.
All doses studied induced high response rates and deep responses. The researchers found that this novel BCMA CAR-T Cell treatment had an excellent safety profile, including doses of approximately 1200×106 CAR-T cells. “This lack of significant toxicity may allow for greater patient access,” Dr Gregory said.
P-BCMA-101 is a novel CAR-T cell therapeutic agent that targets B cell maturation antigen, which is highly expressed on multiple myeloma cells. "It is designed to increase efficacy while minimizing toxicity through reduced immunogenicity, lack of tonic signaling, a safety switch, and a product comprised predominantly of early memory T cells that are effectively all CAR-positive," the authors wrote. "P-BCMA-101 is produced using the piggyBac™ DNA Modification System instead of a viral vector, and requires only plasmid DNA and mRNA. This eliminates the need for virus, is less costly, and produces a purified population of CAR[-positive] cells with a preponderance of the favorable stem cell memory T phenotype."
Disclosures: This study was supported by Poseida Therapeutics. Please refer to the original abstract for a complete list of authors' disclosures.
- Gregory T, Cohen AD, Costello CL, et al. Efficacy and safety of P-Bcma-101 CAR-T cells in patients with relapsed/refractory (r/r) multiple myeloma (MM). Oral presentation at: American Society of Hematology 60th Annual Meeting & Exposition; December 1-4, 2018; San Diego, CA. Abstract 1012.