Bispecific Antibodies: Strategies Available to Optimize Their Safe Delivery in Patients with Multiple Myeloma

Bispecific antibodies (BsAbs) have emerged as an important new class drugs for the treatment of multiple myeloma (MM) over the last few years. Currently, BsAbs are only licensed for use as monotherapy in patients with relapsed/refractory MM who have had at least three prior lines of treatment and are triple class-exposed (patients who have received an anti-CD38 monoclonal antibody, an immunodulatory drug, and a proteasome inhibitor). However, their use in earlier lines, including in the upfront setting, is being explored in multiple ongoing clinical trials with promising early results. The BsAbs have specific toxicities, including a high rate of low-grade cytokine release syndrome and, less commonly, immune effector cell-associated neurotoxicity syndrome. These immune-related toxicities occur almost exclusively during the initiation phase of the BsAbs. This has led to frequent hospitalization of patients for the duration of the initial step-up dosing phase. Strategies that could facilitate outpatient step-up dosing, such as tocilizumab prophylaxis, will become even more critical if BsAbs move into earlier lines of treatment and are used in larger numbers of patients. Optimizing infection prophylaxis is critical for ensuring the safe delivery of BsAbs as infection is the leading cause of non-relapse mortality in patients being treated with BsAbs. Multiple strategies to minimize the infection risk, including antimicrobial prophylaxis, immunoglobulin replacement, vaccination and reduced dosing frequency, have been evaluated. The clinical data on the efficacy of these supportive measures are described in this review article alongside the available strategies for mitigating and managing CRS and ICANS.