Association of adverse events and associated cost with efficacy for approved relapsed and/or refractory multiple myeloma regimens: A Bayesian network meta‐analysis of phase 3 randomized controlled trials

Abstract

BACKGROUND: Several new treatment options have been approved for relapsed and/or refractory multiple myeloma (RRMM). In this systematic review, associations of the efficacy of each approved regimen with adverse events (AEs) and the total cost per cycle were compared with a Bayesian network meta-analysis (NMA) of phase 3 randomized controlled trials (RCTs). METHODS: Scopus, Cochrane, PubMed Publisher, and Web of Science were searched from January 1999 to July 2018 for phase 3 RCTs of regimens (approved by the US Food and Drug Administration) used in RRMM. The relative ranking of agents was assessed with surface under the cumulative ranking (SUCRA) probabilities. The primary efficacy, safety, and cost outcomes were progression-free survival with the regimen, grade 3 to 4 AEs, and the total cost per cycle (regimen cost plus average cost of managing AEs). RESULTS: Fifteen studies including 7718 patients and evaluating 14 different regimens were identified. Daratumumab, lenalidomide, and dexamethasone were ranked highest for reducing progression (hazard ratio, 0.13; 95% credible interval, 0.09-0.19; SUCRA, 1) but carried the highest probability of total cost per cycle ($41,420; 95% Credible Interval [CrCl], $58,665-$78,041; SUCRA, 0.02). Panobinostat, bortezomib, and dexamethasone were the least effective and least safe (SUCRA, 0.24), whereas bortezomib, thalidomide, and dexamethasone emerged as least effective with the highest total cost per cycle (SUCRA, 0.33). Carfilzomib and dexamethasone emerged as the winner when this regimen was considered in terms of efficacy and safety (SUCRA, 0.61) and efficacy and total cost per cycle (SUCRA, 0.60). CONCLUSIONS: The results of this NMA can provide additional guidance for the decision-making process when one is choosing the most appropriate regimen for RRMM.

Monoclonal antibodies in relapsed/refractory myeloma: updated evidence from clinical trials, real-life studies, and meta-analyses

“…Finally, 'financial toxicity' of MoAbs, is a not negligible issue. Appropriate cost-effectiveness models should be developed to estimate the cost and health outcomes of new combined treatments containing MoAbs over a long-time horizon [130]. These analyses should include direct medical costs (treatment acquisition and administration in different lines of treatment, pre-and post-medication, prophylactic therapies and adverse event management), and health-care resource utilization, evaluating lifeyears and quality-adjusted life-years estimations.…”

What The Princess Bride Teaches Us About Outcomes in Multiple Myeloma

“…8 However, increased efficacy of triplet therapy also comes at a costthere is a higher incidence of grade 3 and 4 toxicities and a greater cost burden of treatment. [8][9][10] Thus, the choice between triplet and doublet therapy to treat relapsed MM has to be balanced between patient characteristics, disease features, tolerance, and potential for worsening financial toxicity.…”