Addition of daratumumab to multiple myeloma backbone regimens significantly improves clinical outcomes: a systematic review and meta-analysis of randomised controlled trials

Abstract

Daratumumab has shown clinical benefit in multiple myeloma. We aimed to evaluate the safety and efficacy of adding daratumumab to backbone anti-myeloma treatments. Systematic search was performed up to August 2021 to identify randomised controlled trials comparing the outcomes of backbone therapy with and without daratumumab in relapsed/refractory and newly diagnosed myeloma (RRMM and NDMM, respectively). Odds ratios (ORs) and hazard ratios (HRs) were calculated with 95% confidence intervals (CIs). Primary outcomes were death or disease progression, minimal residual disease (MRD) negativity, and stringent complete response (sCR). Secondary outcomes were complete response or better and safety endpoints prespecified in the study protocol: PROSPERO (CRD42020222904). In NDMM, MRD negativity [OR = 3.61 (CI 2.33–5.61)] and sCR [OR = 2.29 (CI 1.49–3.51)] were more likely and death or disease progression [HR = 0.47 (CI 0.39–0.57)] was less likely to occur with daratumumab compared to control. Regarding RRMM, MRD negativity [OR = 5.43 (CI 2.76–10.66)] and sCR [OR = 3.08 (CI 2.00–4.76)] were more likely and death or disease progression was less likely [HR = 0.50 (CI 0.37–0.67)] with daratumumab compared to control. The addition of daratumumab has shown high clinical efficacy and acceptable toxicity profile for the treatment of NDMM and RRMM regarding the endpoints examined.

Drug Expenditure, Price, and Utilization in US Medicaid: A Trend Analysis for New Multiple Myeloma Medications from 2016 to 2022

“…In a comparison of the three medications, daratumumab emerged as the medication with the highest utilization and reimbursement. This can be attributed to the superior efficacy of daratumumab compared with ixazomib and elotuzumab [ 17 ]. Daratumumab can be used for either newly diagnosed or relapsed MM patients.…”

Indirect Treatment Comparison of Daratumumab, Pomalidomide, and Dexamethasone Versus Standard of Care in Patients with Difficult-to-Treat Relapsed/Refractory Multiple Myeloma

“…The results demonstrated that the daratumumab-containing regimens daratumumab, lenalidomide, and dexamethasone (D-Rd) and D-Vd were more effective in improving PFS when compared with other evaluated regimens. In a recent NMA by Kiss et al [ 25 ], better clinical outcomes were demonstrated in patients with RRMM treated with daratumumab-containing vs control regimens with regards to minimal residual disease negativity, stringent complete response, death, and disease progression. Additionally, in an NMA by Luo et al [ 26 ], which synthesized results from 24 randomized controlled trials, it was demonstrated that D-Rd showed better efficacy than the other regimens with regards to nonresponse rate, time to progression, and PFS.…”

Az elérhető gyógyulás küszöbén: innovációk a myeloma multiplex kezelésében

“…A klinikai vizsgálatok alapján a legígéretesebb túlélési eredményeket az RVd-protokoll CD38-ellenes monoklonális antitesttel (daratumumab, isatuximab) való kiegészítésével érhetjük el. Fontos azonban megjegyezni, hogy a kvadruplet terápia a hematológiai toxicitás és az infekciók gyakoriságának növekedésével jár [23][24][25].…”