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Introduction: Recent advances and drug approvals in the last decade have substantially changed the landscape of relapsed and refractory multiple myeloma (RRMM), which not only improved outcomes for patients but also increased complexity of treatment decisions. The approvals are based on randomized studies of novel agents added to an immunomodulatory drug- (IMiD) or proteasome inhibitor (PI)-backbone showing an improvement in outcomes. However, differences in enrolled patient populations/study designs limit comparisons of results, making the choice and sequencing of agents challenging., Areas Covered: This review summarizes the latest updates of key clinical trials of IMiD- and PI-backbone regimens in RRMM. Additionally, it highlights carfilzomib dosing strategies and toxicity profiles of varying carfilzomib combination regimens and provides a clinical guideline for the use of carfilzomib therapy. PubMed and relevant meeting (ASH, ASCO, EHA, IMW) databases from 2010 to 2020, as well as clinicaltrials.gov, were queried for this review., Expert Opinion: The choice of therapy for RRMM requires careful consideration of patient factors (age/frailty and comorbidities), disease factors (symptom burden/biology), and treatment-related factors (toxicities/responses to prior therapies). Importantly, a critical factor in selecting an agent based on the published data is a patient's sensitivity to lenalidomide and bortezomib at the time of relapse.

Background: The prognosis of patients with systemic light chain (AL) amyloidosis, particularly cardiac, is poor. Treatments have been derived from multiple myeloma, but there are few studies that use triplet regimens in AL amyloidosis because of concern of greater toxicity than seen in myeloma., Patients and Methods: We conducted a retrospective review of patients with newly diagnosed AL amyloidosis who were initially treated with a triplet regimen., Results: For the 9 patients included, the median age was 64 years, and 8 were ineligible for stem cell transplantation. At least 2 organs were involved in 4 patients, including 7 with kidney and 4 with heart involvement, 2 of whom had New York Heart Association class 3 heart failure. All the patients received bortezomib, cyclophosphamide or lenalidomide/thalidomide, and dexamethasone. With a median follow-up of 13 months, 8 of 9 patients had a hematologic response, including 2 who achieved complete response, with a median time to response of 2.7 months. An organ response was seen in 7 of 9 patients, including all 4 patients with cardiac involvement. There were no deaths, and only 1 patient had progressive disease. The major toxicity observed was fluid overload and syncope, seen only in patients with heart failure, who eventually achieved a partial or complete response., Conclusions: Dose-attenuated triplet regimens achieved rapid hematologic responses with manageable and reversible toxicity in patients with newly diagnosed AL amyloidosis., (Copyright © 2013 Elsevier Inc. All rights reserved.)