Abstract
Anti-CD38 monoclonal antibodies (mAbs), including daratumumab and isatuximab, have become key components of treatment for relapsed/refractory multiple myeloma (RRMM). This expert consensus provides evidence-based guidance on their optimal use, including regimen selection, special considerations for elderly or frail patients, and the treatment of high-risk subgroups. Key topics addressed include the selection of anti-CD38-based regimens, patient stratification by frailty and comorbidities, strategies for managing hematologic toxicities, and considerations for re-treatment. Anti-CD38 mAb-based regimens have demonstrated clinical efficacy across diverse RRMM populations, including patients with high-risk cytogenetic abnormalities such as 1q21+. While resistance remains a clinical challenge, particularly in previously exposed patients, current evidence supports the feasibility of anti-CD38 mAb rechallenge following a substantial washout period (typically 6 to 12 months), which may allow partial recovery of CD38 expression and immune effector function. The consensus also emphasizes the continued utility of these agents in elderly or frail individuals, where durable responses can be achieved with appropriate monitoring and supportive care. Moreover, anti-CD38 mAbs are recognized as key components within evolving treatment paradigms, supporting their use for combination strategies involving emerging immunotherapies such as CAR-T cells and bispecific antibodies. This consensus provides a framework to guide individualized treatment decisions and highlights the need for continued research to optimize the integration of anti-CD38 mAbs into the modern therapeutic landscape of RRMM.