Optimal Sequencing Strategies for CAR T and Bispecifics in R/R MM
Panelists discuss the critical role of sequencing B-cell maturation antigen (BCMA)-targeted therapies in multiple myeloma, emphasizing that administering chimeric antigen receptor (CAR) T-cell therapy before bispecific antibodies leads to better outcomes, while real-world evidence and emerging guidelines increasingly inform strategic decisions based on treatment timing, disease urgency, and patient-specific factors.
The discussion focused on the sequencing of BCMA-targeted therapies in multiple myeloma, highlighting how prior treatment with BCMA agents—such as bispecific antibodies or antibody-drug conjugates—can impact the efficacy of subsequent CAR T-cell therapy. Clinical trials leading to the approval of these agents excluded patients previously exposed to other BCMA therapies, but real-world data has shown that prior use, particularly within 6 months before CAR T, may reduce CAR T efficacy. Possible mechanisms include BCMA downregulation or loss and T-cell exhaustion, underscoring the importance of strategic sequencing.
Experts emphasized that current evidence supports administering CAR T therapy before bispecifics when possible. Patients who respond to CAR T therapy often retain sensitivity to BCMA-targeted bispecifics upon relapse, with studies showing progression-free survival exceeding 18 months in such scenarios. In contrast, outcomes are generally worse when patients receive bispecific antibodies first, then attempt CAR T. This pattern is further supported by real-world data and emerging consensus guidelines that recommend CAR T first, when access and patient condition allow.
Nonetheless, there are situations where bispecifics may precede CAR T therapy. These include limited access to CAR T, urgent disease progression requiring immediate treatment, or patient preference due to logistical challenges, such as lack of caregiver support. In these cases, bispecifics may be used as “bridging” or “holding” therapy, though ideally not before T-cell collection to avoid compromising CAR T product quality. A recent consensus paper clarified terminology around “holding therapy” (before apheresis) and “bridging therapy” (between apheresis and infusion), recommending bispecifics like talquetamab primarily in the bridging phase. This evolving body of real-world evidence continues to guide clinical decisions in sequencing immunotherapies for optimal outcomes in relapsed/refractory multiple myeloma.
Newsletter
Stay up to date on recent advances in the multidisciplinary approach to cancer.
Toxicity After Chemo May be Avoided With Anastrozole Combo in Breast Cancer
December 25th 2023It may be possible to use anastrozole plus palbociclib, trastuzumab, and pertuzumab in place of chemotherapy in the frontline setting for hormone receptor–positive, HER2-positive metastatic breast cancer, says Amy Tiersten, MD.
Recap: Recent Advances in the Treatment of Metastatic Castration-Sensitive Prostate Cancer
September 18th 2022Expert oncologists review key studies in the metastatic castration-resistant prostate cancer treatment landscape and discuss how evidence can be applied to clinical practice to improve patient outcomes.
