OBJECTIVES: Even though relapsed/refractory multiple myeloma (RRMM) is incurable, many novel treatments have been developed in the last 5 years. Our goal was to conduct a targeted literature review analyzing all indirect comparisons based on effectiveness of RRMM therapies.

METHODS: The search was conducted using PubMed from January 2017 till December 2023. Full text data was extracted from 21 studies after title and abstract screening and deduplication of 36 identified abstracts.

RESULTS: Out of 21 studies, 59% (n=13) were pairwise meta-analysis and 41% (n=9) were network meta-analysis. Immunomodulatory drugs (IMiD) e.g. (lenalidomide, pomalidomide) were assessed in 42% (n=9) studies, monoclonal antibodies (mAB) (e.g. daratumumab, elotuzumab, isatuximab) in 38% (n=8), proteasome inhibitors (PI) (e.g. bortezomib ixazomib) 14% (n=3). Treatments were either monotherapy or combination therapy. Other therapies included chimeric antigen receptor T-cell therapy (14%; n=3), B-cell lymphoma-2 inhibitor (e.g. venetoclax) (5%; n= 1) and histone deacetylase inhibitors (e.g. panobinostat, vorinostat, ricolinostat) (5%; n=1). Progression-free survival (PFS) was the most reported efficacy outcome in 86% (n=18) studies, followed by overall survival (OS) in 76% (n=16) and overall response rate in 57% (n=12). Other efficacy endpoints reported were complete response rate in 24% (n=5), minimal residual disease in 14% (n=3), and very good partial response in 10% (n=2) studies. 10% studies (n=2) reported higher OS and PFS in triplet therapy (daratumumab +lenalidomide +dexamethasone) compared to doublet therapy (lenalidomide +dexamethasone) or monotherapy. 20% (n=4) studies on mABs demonstrated better OS and PFS compared to PIs and IMiDs. 10% (n=2) reported IMiD with better OS and PFS when compared to placebo and control group.

CONCLUSIONS: Our TLR of the comparative effectiveness analysis in RRMM, suggests that mAB + IMiD triplet regimen has better effectiveness than IMiD doublet, followed by mABs or IMiDs or PIs monotherapy.