The Safety of Bridging Radiation with Anti-BCMA CAR T-Cell Therapy for Multiple Myeloma.

Abstract

PURPOSE:

B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR) T cells (CART-BCMA) are a promising treatment for relapsed/refractory multiple myeloma (r/rMM). We evaluated the safety and feasibility of bridging radiation (RT) in subjects treated on a phase I trial of CART-BCMA.

EXPERIMENTAL DESIGN:

Twenty-five r/rMM subjects were treated in three cohorts with two doses of CART-BCMA cells ± cyclophosphamide. We retrospectively analyzed toxicity, response, and CART manufacturing data based on RT receipt.

RESULTS:

Thirteen subjects received no RT <1 year before CART infusion (Group A). Eight subjects received RT <1 year before CART infusion (Group B) with median time from RT to apheresis of 114 days (range 40-301). Four subjects received bridging-RT (Group C) with a median dose of 22 Gy and time from RT to infusion of 25 days (range 18-35). Group C had qualitatively lower rates of grade 4 (G4) hematologic toxicities (25%) versus A (61.5%) and B (62.5%). G3-4 neurotoxicity occurred in 7.7%, 25%, and 25% in Group A, B, and C, respectively. G3-4 cytokine release syndrome was observed in 38.5%, 25%, and 25% in Group A, B, and C, respectively. Partial response or better was observed in 54%, 38%, and 50% of Group A, B, and C, respectively. RT administered <1 year (P = 0.002) and <100 days (P = 0.069) before apheresis was associated with lower in vitro proliferation during manufacturing; however, in vivo CART-BCMA expansion appeared similar across groups.

CONCLUSIONS:

Bridging-RT appeared safe and feasible with CART-BCMA therapy in our r/rMM patients, though larger future studies are needed to draw definitive conclusions.

• Authors: Shwetha H Manjunath, Adam D Cohen, Simon F Lacey, Megan M Davis, Alfred L Garfall, J Joseph Melenhorst, Russell Maxwell, W Tristram Arscott, Amit Maity, Joshua A Jones, John P Plastaras, Edward A Stadtmauer, Bruce L Levine, Carl H June, Michael C Milone, Ima Paydar
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 27 Issue 23 Pg. 6580-6590 (12 01 2021) ISSN: 1557-3265 [Electronic] United States
• PMID: 34526365 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: ©2021 American Association for Cancer Research.

Chemical References

• B-Cell Maturation Antigen
• Receptors, Chimeric Antigen

Topics

• B-Cell Maturation Antigen
• Humans
• Immunotherapy, Adoptive (adverse effects)
• Multiple Myeloma (drug therapy)
• Receptors, Chimeric Antigen
• Retrospective Studies