# Daratumumab, Lenalidomide, and Dexamethasone Versus Bortezomib, Lenalidomide, and Dexamethasone in Transplant‐Ineligible Newly Diagnosed Multiple Myeloma: A Systematic Literature Review and Meta‐Analysis

## TL;DR

This study compares two treatment regimens for newly diagnosed multiple myeloma patients who are not eligible for transplants and finds that one combination may be more effective.

## Contribution

The study provides a meta-analysis comparing DRd and VRd regimens for transplant-ineligible multiple myeloma patients using systematic literature review.

## Key findings

- DRd showed a lower risk of disease progression or death compared to VRd using a naïve approach (HR: 0.60).
- Adjusted analysis confirmed DRd's benefit with a hazard ratio of 0.56, accounting for study limitations.
- The findings may guide treatment selection in the absence of direct clinical trials comparing DRd and VRd.

## Abstract

Daratumumab in combination with lenalidomide and dexamethasone (DRd) and bortezomib in combination with lenalidomide and dexamethasone (VRd) are guideline‐recommended preferred regimens for initial treatment of transplant‐ineligible (TIE) patients with newly diagnosed multiple myeloma (NDMM). This study aimed to systematically identify evidence on the clinical effectiveness of DRd and VRd as first‐line treatments for patients with TIE NDMM and to conduct a meta‐analysis. Ovid MEDLINE, Embase, and Cochrane Library were searched from January 2019 to June 2023, along with key congresses from January 2018 to June 2023. Bibliographies of relevant systematic literature reviews (SLR) were hand‐searched. Randomized controlled trials and appropriately adjusted non‐randomized studies comparing DRd versus VRd as first‐line treatment for TIE NDMM were included. Overall, five records from three unique studies were identified. The fixed‐effects meta‐analysis showed a lower risk of disease progression or death with DRd versus VRd using the naïve approach (hazard ratio [HR]: 0.60; 95% confidence interval [CI]: 0.46, 0.77) as well as with the adjusted approach, which accounted for both double counting (i.e., two studies shared one comparison) and variance inflation due to studies with moderate and high risk of bias (HR: 0.56; 95% CI: 0.39, 0.82). In the absence of clinical trials with head‐to‐head comparison of these treatment regimens, these results could help inform the selection of optimal first‐line treatment for TIE NDMM patients.