Advancing multiple myeloma therapy: A systematic analysis of corticosteroids and monoclonal antibodies as dual therapeutic agents

BACKGROUND: Multiple myeloma (MM) is an incurable hematopoietic malignancy defined by the bone marrow's clonal expansion of neoplastic plasma cells. Corticosteroids and monoclonal antibodies (mAbs) have been approved for the treatment of MM over the past 20 years and are now key components of treatment regimens, improving clinical outcomes. Corticosteroids (dexamethasone and prednisone) are frequently used in combination with other agents [proteasome inhibitors and immunomodulatory drugs (IMiDs)], while mAbs (daratumumab, elotuzumab, and isatuximab) have transformed treatment paradigms, particularly for relapsed/refractory cases. AIM: To evaluate the impact of corticosteroids and mAbs on the treatment of MM. METHODS: This systematic review integrates results from randomized controlled trials and cohort studies published from 2003 to 2024. This resulted in the identification 26 articles assessing the role of corticosteroids and mAbs in various treatment settings: Newly diagnosed, relapsed, and refractory MM. Seventeen studies were included in the systematic review. RESULTS: We show that corticosteroid-based combination regimens are critical for achieving rapid tumour regression and increasing overall survival (OS) when combined with proteasome inhibitors (bortezomib or carfilzomib). Moreover, mAb therapy, particularly with daratumumab, has also led to significant benefits, enhancing progression-free survival and OS when added to first- and later-line therapy. All IMiDs and proteasome inhibitors offer activity when combined with daratumumab, with the efficacy being better with daratumumab, even in higher-risk patients. However, treatment of high-risk MM, including those with extramedullary disease and patients with adverse genetics, still poses challenges. CONCLUSION: While great strides have been made in the treatment, much remains to be learned about long-term safety, efficacy, and potential resistance mechanisms to these treatments.