Outcomes of lenalidomide‐ or bortezomib‐based regimens in older patients with plasma cell myeloma

Abstract

The “triplet” regimen of lenalidomide, bortezomib, and dexamethasone (RVD) showed survival advantage over lenalidomide‐dexamethasone (RD) in clinical trials, but older patients with myeloma often receive doublet regimens (RD or bortezomib‐dexamethasone, VD), or VD plus cyclophosphamide (VCD). We compared these first‐line regimens using real‐world data from Medicare beneficiaries receiving therapy between 2007 and 2015. In each comparative analysis, we balanced confounding characteristics using a propensity score. Outcomes included overall (OS) and event‐free survival (EFS, reporting hazard ratios [HR] with 95% confidence intervals [CI]), adverse events, and costs. We identified 6076 patients with median age 76 and median OS of 2.6 years. In the comparison of RVD vs RD/VD doublets, RVD showed significantly better OS (HR = 0.83; 95% CI, 0.72‐0.95) and EFS (HR = 0.68; 95% CI, 0.61‐0.76). So, RVD was associated with more frequent hospitalizations, anemia, and neuropathy, but no increase in thromboembolism or secondary cancers. Costs were higher with RVD. In the comparison of RD vs VD, RD demonstrated better EFS (HR = 0.74; 95% CI, 0.68‐0.81) and marginally better OS (HR = 0.91; 95% CI, 0.83‐0.99). And, RD resulted in significantly more thromboembolic events, less neuropathy, and no significant difference in hospitalizations, transfusions, or secondary cancers. In the comparison of VCD vs VD, we observed no significant difference in any outcome. Superior survival favors RVD over doublet regimens, but even in 2015 RVD was applied for only about 25% of Medicare beneficiaries with myeloma. For patients not eligible for RVD due to toxicity, VCD offers no survival benefit over VD. Lenalidomide‐dexamethasone may be the preferred line doublet considering its advantage over VD.

Functional Status Associations With Treatment Receipt and Outcomes Among Older Adults Newly Diagnosed With Multiple Myeloma

“…Triplet therapy was defined via claims for two agents in different therapeutic classes within a 60-day interval, with the assumption that corticosteroids were concurrently administered as a third medication. 20…”

“…The numeric responses to each item were summed, yielding a total score ranging from 0 (no functional disability) to 40 (most disabled). Individuals were categorized by cohort distributional breakpoints as having mild (score 0-9), moderate (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25), or severe (26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40) disability on the basis of two patterns in the observed data. These included an apparent bimodal distribution of OASIS scores with a long right tail in the cohort (Appendix Fig A1) and an apparent inflection point in the frequency of receiving any MM therapy at an OASIS score of 26 (Appendix Fig A2).…”

The real-world outcomes of multiple myeloma treated with elotuzumab, pomalidomide, and dexamethasone

“…Daratumumab is now being used in a substantial population of patients with the recent approval of its use in both transplant-ineligible newly diagnosed MM patients [29,30] and RRMM patients [31]. Although daratumumab is now represented as standard, rst-line therapy for transplant-ineligible MM patients [29,30], a considerable population of real-world patients receive twodrug regimens as rst-line therapy (e.g., bortezomib-dexamethasone or lenalidomide-dexamethasone) due to their age and frailty [8,32]. The results of our study suggest that EPd may be an attractive treatment option in this patient group after they become refractory to their rst-line doublet therapy.…”

Effect of Lenalidomide on Pentylenetetrazole-Induced Clonic Seizure Threshold in Mice: A Role for N-Methyl-D-Aspartic Acid Receptor/Nitric Oxide Pathway

“…For instance, thalidomide can result in peripheral neuropathy by its cumulative dose, whereas lenalidomide rarely exhibits such side effect. 2,4 Lenalidomide, when orally administrated, can penetrate the cerebrospinal fluid and be used for the central nervous system (CNS) malignancies in children. 5 Neuroprotective effects of lenalidomide have also been shown in preclinical studies on neurodegenerative diseases such as amyotrophic lateral sclerosis 6 and Parkinson's disease.…”