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Early versus late treatment for smoldering (asymptomatic) multiple myeloma: A systematic review.
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).
Background: Expectant management remains the current standard of care for patients with smoldering multiple myeloma (SMM). Recent appreciation of "high risk" smoldering myeloma and the advent of novel therapeutic agents may allow one to better tailor the timing of therapeutic interventions. Herein, we performed a systematic review of the literature, summarizing the available randomized controlled trial (RCT) evidence for treatment of SMM. Methods: Our systematic search strategy includes MEDLINE, EMBASE, Cochrane Database, and relevant bibliographies where the following search concepts were used: RCT, SMM as defined as per the IMW Criteria, and treatment. Two reviewers independently extracted data on study design, population, sample size, treatment, clinical outcomes, and trial quality, were any discrepancies were discussed and resolved. Results: We identified 7 RCTs (2 articles and 5 abstracts) representing 869 patients. Six articles compared early versus deferred treatment for SMM; 2 studies compared early Melphalan plus Prednisone (MP) versus deferred MP. 3 studies compared bisphosphonates versus abstention while one study compared lenalidomide with dexamethasone to therapeutic abstention. Further, one study compared thalidomide with zoledronate to zoledronate alone. The median age is 66. Four studies received a Jadad score of 3 while three studies received a score of 2. Allocation concealment was described in four studies. Risk of disease progression was lower in patients receiving therapy compared to abstention OR 0.5(0.38-0.68). The events that demonstrate disease progression were not clearly defined. Further, the use of combination therapy compared to a single intervention decreased the risk of progression OR 0.23(0.11-0.51). No difference in OS was noted in patients receiving therapy compared to abstention OR 0.95(0.57-1.57). Conclusions: Early treatment of SMM compared with abstention decreases the risk of disease progression. However, OS was not improved by earlier intervention. High risk SMM may benefit from early intervention. The optimal intervention(s) remains to be defined, and further studies are warranted in this understudied population.