Salvage therapies in relapsed and/or refractory myeloma: what is current and what is the future?

Abstract

The treatment landscape for multiple myeloma (MM) is evolving with our understanding of its pathophysiology. However, given the inevitable cohort heterogeneity in salvage therapy, response to treatment and overall prognoses tend to vary widely, making meaningful conclusions about treatment efficacy difficult to derive. Despite the hurdles in current research, progress is underway toward more targeted therapeutic approaches. Several new drugs with novel mechanism of action and less toxic profile have been developed in the past decade, with the potential for use as single agents or in synergy with other treatment modalities in MM therapy. As our discovery of these emerging therapies progresses, so too does our need to reshape our knowledge on knowing how to apply them. This review highlights some of the recent landmark changes in MM management with specific emphasis on salvage drugs available for relapsed and refractory MM and also discusses some of the upcoming cutting-edge therapies that are currently in various stages of clinical development.

Adverse event management in patients with relapsed and refractory multiple myeloma taking pomalidomide plus low‐dose dexamethasone: A pooled analysis

“…Patients with relapsed and refractory multiple myeloma (RRMM) are usually older, have advanced disease, and may present with disease‐related comorbidities, such as myelosuppression, bone disease, or renal impairment, which may make further treatment and adverse event (AE) management difficult . Because of a high disease burden, lasting effects of prior treatment, and comorbidities, patients with RRMM are more susceptible to treatment‐related AEs than patients with newly diagnosed MM . This is in part due to exposure to multiple prior therapies, resulting in an increased risk for common treatment‐related AEs, including neutropenia, peripheral neuropathy, thrombocytopenia, anemia, and infection .…”

“…Because of a high disease burden, lasting effects of prior treatment, and comorbidities, patients with RRMM are more susceptible to treatment‐related AEs than patients with newly diagnosed MM . This is in part due to exposure to multiple prior therapies, resulting in an increased risk for common treatment‐related AEs, including neutropenia, peripheral neuropathy, thrombocytopenia, anemia, and infection . Infection is a particularly challenging treatment‐emergent AE because it is a leading cause of morbidity and death in patients with RRMM .…”

“…Infection is a particularly challenging treatment‐emergent AE because it is a leading cause of morbidity and death in patients with RRMM . Another potentially serious AE is venous thromboembolism, which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), but DVT and PE are infrequent due to active prophylaxis . Given the advanced nature of disease, patients with RRMM should be monitored closely and carefully managed during treatment.…”

“…12,13 Another potentially serious AE is venous thromboembolism, which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), but DVT and PE are infrequent due to active prophylaxis. [1][2][3]5,9,12 Given the advanced nature of disease, patients with RRMM should be monitored closely and carefully managed during treatment.…”

Carfilzomib boosted combination therapy for relapsed multiple myeloma

“…In fact, 5-year survival rates have almost doubled, increasing from 27% to 47% between 1989 and 2010, respectively. 2 , 3 …”