Date of Award
Selective Evidence-Based Medicine Review
Master of Science in Health Sciences - Physician Assistant
Physician Assistant Studies
OBJECTIVE: The objective of this selective EBM review is to determine whether or not “the combination of a proteasome inhibitor, lenalidomide, and dexamethasone reduce fatigue in patients with relapsed or refractory multiple myeloma (RRMM)?”
STUDY DESIGN: A systematic review of three English language open-label clinical trials with one published in 2013 and two published in 2016.
DATA SOURCES: Two randomized open-label, phase 3 clinical trials and one open-label phase 2 cohort study found using PubMed and Cochrane Library. All sources were published in peer-reviewed journals.
OUTCOME MEASURED: Fatigue was the outcome measured in all three studies utilizing Common Terminology Criteria for AEs (version 3.0) or European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire core 30 module (EORTC QLQ-C30) and myeloma-specific module (QLQ-MY20).
RESULTS: In the cohort study conducted by Wang et al. (Blood. 2013;122(18):3122–3128. doi:10.1182/blood-2013-07-511170.), showed no reduction in fatigue in the maximum planned dose (MPD) of carfilzomib, lenalidomide, and dexamethasone group compared to the other cohorts. The MPD group reported fatigue 69.2% compared to 65.5% overall. The RCT performed by Stewart et al. (J Clin Oncol. 2016;34(32):3921–3930. doi:10.1200/JCO.2016.66.9648.) found no statistical significance in reduction of fatigue between the carfilzomib, lenalidomide, and dexamethasone (KRd) group and control group (-0.46 in favor of KRd, p=0.71); however, both groups had statistically significant mean change from baseline of worsening fatigue in multiple cycles (p<0.05). Lastly, in a double-blind RCT by Moreau et al. (N Engl J Med. 2016;374(17):1621–1634. doi:10.1056/NEJMoa1516282.), there was no significant difference in fatigue reduction between the ixazomib group and placebo group.
CONCLUSIONS: Based on analysis of these studies, the combination of a proteasome inhibitor, lenalidomide, and dexamethasone does not reduce fatigue in patients with relapsed or refractory multiple myeloma. Future studies need to be designed in order to evaluate the effectiveness in fatigue reduction in patient with relapsed or refractory multiple myeloma.
LaRosa, Jessica I., "Does the Combination of a Proteasome Inhibitor, Lenalidomide, and Dexamethasone Reduce Fatigue in Patients with Relapsed or Refractory Multiple Myeloma?" (2021). PCOM Physician Assistant Studies Student Scholarship. 578.