Updates on safety and efficacy of maintenance therapy after autologous stem cell transplantation in newly diagnosed multiple myeloma: A systematic review.

Abstract

e20503 Background: Multiple Myeloma (MM) is treatable but an incurable hematological malignancy, requiring additional approaches such as maintenance therapy (MT) after autologous-stem cell transplantation. MT aids to achieve deepened response, sustained response and prolongs progression-free survival (PFS) but has a controversy over its overall survival (OS) benefit. Within the last decade, there have been innovative efforts tested for MT. We designed a systematic review to evaluate the current evidence on this topic. Methods: PubMed and Embase were searched for articles published on MT between 01/2010 and 12/2018 and PRISMA guidelines were used to evaluate 76,588 articles on PubMed and 1516 articles on Embase. Thirty-three articles were included in systematic review. Results: Thirteen articles were available on lenalidomide-MT whereas six articles each on thalidomide and proteasome inhibitors, five articles on combination therapy, two articles on miscellaneous and one article on elotuzumab were available, including trials and observational studies. MT (thalidomide 50 mg, lenalidomide 10 mg) was given for a variable period, commonly used till relapse, progression or unacceptable toxicity. Thalidomide showed consistent PFS-benefit but no OS benefit and had significant neurotoxicity, responsible for discontinuations or dose reductions. Lenalidomide had evidence for both, improved PFS and some evidence for better OS and had hematotoxicity, mainly neutropenia which required dose reductions. Secondary primary malignancies were more frequent with lenalidomide. Longer maintenance of lenalidomide was associated with more toxicity. Thalidomide-bortezomib combination had better PFS than thalidomide alone but no OS benefit. Bortezomib-MT improved OS in high-risk patients and renal failure and had dose-dependent toxicity. Bortezomib-MT after bortezomib-based induction was better than thalidomide-based-MT after cytotoxic induction. MT was associated with the achievement of negative MRD-status. Ixazomib was effective and feasible with improved PFS. Combination of bortezomib-lenalidomide-dexamethasone MT was beneficial in high-risk patients. Conclusions: MT improves PFS with limited evidence toward improved OS. For better outcomes, lenalidomide-based-MT should be given routinely; adjustment of dose might be required due to neutropenia. High-risk patients can get benefit from combination therapy. Role of combination MT needs to be further explored in large prospective studies.

Salvage therapy with “Dara‐KDT‐P(A)CE” in heavily pretreated, high‐risk, proliferative, relapsed/refractory multiple myeloma

“…In this context, 2 (5%), 24 (63%), 9 (24%), and 3 (8%) patients were treated with carfilzomib at doses of 20, 27, 36, and 56 mg/m 2 BSA IV twice weekly, respectively. The majority of our patients ( n = 28, 73%) received thalidomide 100 mg qd orally, because thalidomide showed less hematotoxicity than other IMiDs such as lenalidomide and/or pomalidomide 19 . We replaced thalidomide with pomalidomide 2 or 4 mg qd orally in 10 (27%) patients with sufficient hematopoiesis that had tolerated thalidomide well in the first cycle.…”

“…The majority of our patients (n = 28, 73%) received thalidomide 100 mg qd orally, because thalidomide showed less hematotoxicity than other IMiDs such as lenalidomide and/or pomalidomide. 19 We replaced thalidomide with pomalidomide 2 or 4 mg qd orally in 10 (27%) patients with sufficient hematopoiesis that had tolerated thalidomide well in the first cycle. Doxorubicin was not given in the majority of the patients (n = 29, 76%), as experience from our institution had demonstrated markedly increased risk of cardiac AEs after concomitant administration of doxorubicin and carfilzomib.…”