Network Meta-Analysis of Treatment Regimens for Relapsed/Refractory Multiple Myeloma

In this systematic review published in Cancer, researchers looked at the associations of the efficacy of each approved treatment regimen for relapsed and/or refractory multiple myeloma with adverse events (AEs) and the total cost per cycle compared with a Bayesian network meta-analysis of phase III randomized controlled trials (RCTs).

The researchers indicated that the results of the network meta-analysis could provide additional guidance for the decision-making process when clinicians are deciding on the most appropriate regimen for relapsed and/or refractory multiple myeloma. 

“To our knowledge, this is the first [network meta-analysis] that has indirectly evaluated the efficacy, safety, and total treatment cost of a myriad of approved [relapsed and/or refractory multiple myeloma] regimens using phase III RCTs,” the authors wrote. 

Using Scopus, Cochrane, PubMed Publisher, and Web of Science, researchers searched for phase III RCTs of regimens approved by the FDA for relapsed and/or refractory multiple myeloma from January 1999 to July 2018. The relative ranking of agents was then evaluated with surface under the cumulative ranking (SUCRA) probabilities. Moreover, the primary efficacy, safety, and cost outcomes were identified as progression-free survival with the regimen, grade 3 to 4 AEs, and the total cost per cycle (regiment cost plus average cost of managing AEs). 

Overall, 15 studies of 7,718 patients evaluating 14 different regimens were identified. Daratumumab, lenalidomide, and dexamethasone were ranked highest for reducing progression (hazard ratio, 0.13; 95% credible interval [CrCI], 0.09-0.19; SUCRA, 1), but carried the highest probability of total cost per cycle ($41,420; 95% CrCI, $58,665-$78,041; SUCRA, 0.02). 

Further, panobinostat, bortezomib, and dexamethasone were found to be the least effective and least safe (SUCRA, 0.24), whereas bortezomib, thalidomide, and dexamethasone emerged as the least effective with the highest total cost per cycle (SUCRA, 0.33). Carfilzomib and dexamethasone appeared to be the winner though when this regimen was considered in terms of efficacy and safety (SUCRA, 0.61) and efficacy and total cost per cycle (SUCRA, 0.60). 

Notably, because of the heterogeneity of the agents studied and the patient populations used in the analysis, the results are subject to potential biases. The results may also underestimate the costs of newer drugs due to the potentially faster rates of price increases for more expensive drugs. Additionally, the standard of care for relapsed and/or refractory multiple myeloma has changed, including the drug administration and dosing. 

According to the researchers, future detailed studies using comprehensive claims data are needed to better understand this attribute in cost trends for expensive drug treatments.

“By analyzing a large set of claims, we expect that we will be able to develop sufficiently sized samples that provide both strong power and significance while also ensuring homogenous data that will eliminate many of the limitations of our analysis and earlier meta-analyses related to cancer treatments’ efficacy and cost-effectiveness,” the authors wrote. “Mainly, we will be better able to reduce any biases that could occur because of eligibility differences that might exist across various randomized clinical trials.” 

Additionally, the researchers indicated that they may be able to examine a more comprehensive set of indirect costs for various treatment regimens that were not already captured in the data. A prospective analysis that incorporates real-time assessments of the costs, both direct and indirect, and AEs would be ideal to provide a clear and definitive answer.

Reference:

Dhakal B, Narra RK, Giri S, et al. Association of Adverse Events and Associated Costs With Efficacy for Approved Relapsed and/or Refractory Multiple Myeloma Regimens: A Bayesian Network Meta-Analysis of Phase 3 Randomized Controlled Trials. Cancer. doi:10.1002/cncr.32831.