Optimizing the Real-World Use of BCMA-Targeted T-Cell-Engaging Therapies in Patients with Triple-Class-Exposed Relapsed/Refractory Multiple Myeloma: An Italian Modified Delphi Consensus
Michele Cavo, Melissa Bersanelli, Alessandro Corso, Carlotta Galeone, Silvia Mangiacavalli, Roberto Mina, Renato Zambello, Elisabetta Antonioli, Angelo Belotti, Cirino Botta, Gabriele Buda, Francesco Di Raimondo, Monica Galli, Francesca Gay, Massimo Offidani, Maria Teresa Petrucci, Alessandra Romano, Elena Zamagni, Antonella Semeraro, Barbara Veggia, Paolo MarianiBackground/Objectives: The treatment landscape of relapsed/refractory multiple myeloma (RRMM) has significantly evolved with the introduction of novel classes of agents and, more recently, of T-cell-redirecting therapies, including bispecific antibodies (BsAbs). It is essential to enhance and harmonize the therapeutic management of BsAbs within clinical practice. Methods: We performed a modified Delphi expert consensus study on the use of BsAbs targeting the B-Cell Maturation Antigen (BCMA) in patients with triple-class-exposed (TCE) RRMM. The study was conducted in April–November 2025 following established guidelines and best practices for defining consensus. The key phases in the use of anti-BCMA BsAbs were identified and explored. Results: Fifteen Italian hematologists with expertise in the care of TCE RRMM completed two Delphi rounds. Agreement (defined as ≥67% of panelists) was achieved on most of the topics evaluated. In particular, all panelists considered the step-up dosing phase feasible in an outpatient setting, under specific circumstances, and dosing de-escalation in responding patients to reduce the risk of adverse events. For most of them, anti-BCMA BsAb treatment is also feasible in several challenging subgroups, including frail patients (93% agreement) and those with high-risk cytogenetics (93%), extramedullary disease (93%), end-stage renal disease (86%), active plasma cell leukemia (79%), and central nervous system involvement (67%). In addition, agreement (93%) was reached on the possible sequential use of BCMA-targeting therapies, preferentially BsAbs following CAR-T, though a switch in the target antigen should primarily be considered. Conclusions: In this article, we address the main challenges related to the real-world use of anti-BCMA BsAbs in patients with TCE RRMM, offering expert recommendations to complement existing guidelines and support clinical practice.