Next-generation immunomodulatory drugs in multiple myeloma

Abstract

Multiple myeloma (MM) is a hematological malignancy that mainly affects elderly patients, with the median age of 69 years at the time of diagnosis. Despite the recent increase in the number of drugs used in the antimyeloma therapy, the disease remains incurable, with remissions and subsequent relapses. Immunomodulatory drugs (IMIDs), known to have multiple mechanisms of actions, including direct anti-MM activity and immune-stimulatory properties, are currently the backbone in multidrug regimens. New generation IMIDs are recommended nowoby ESMO – lenalidomide is included in frontline therapy, while pomalidomide is accepted from the third line. Clinical trials proved lack of apparent cross-resistance between immunomodulatory agents, confirmed their high efficacy and acceptable safety profile in individuals with relapsed multiple myeloma (RRMM) refractory to proteasome inhibitors and lenalidomide, even with adverse cytogenetic abnormalities. Also, triplet pomalidomide-based combinations with bortezomib, carfilzomib, cyclophosphamide, daratumumab or elotuzumab were proved to be effective and safe in this group of patients. The most common adverse events of the new generation IMIDs are the following: hematological toxicity (neutropenia, thrombocytopenia, anemia), fatigue and, while administered with dexamethasone, infections. However, peripheral neuropathy, significantly limiting the use of first generation IMID - thalidomide, is much less frequently observed. Due to the increased risk of venous thromboembolism, thromboprophylaxis should be implemented in the whole course of IMID therapy. Data from real-life settings demonstrate that new generation IMIDs are a cost-effective treatment option in relapsed/ refractory myeloma. Currently, one drug program with the new IMIDs is available in Poland.