Optimizing the Real-World Use of BCMA-Targeted T-Cell-Engaging Therapies in Patients with Triple-Class-Exposed...

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.

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.

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.

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.