Relative efficacy of treatment options in transplant-ineligible newly diagnosed multiple myeloma: results from a systematic literature review and network meta-analysis

Abstract

Established treatments for transplant-ineligible (TNE) patients with newly diagnosed multiple myeloma (NDMM) include melphalan and prednisone (MP) combined with either bortezomib (VMP) or thalidomide (MPT), or lenalidomide plus low-dose dexamethasone (Rd). New treatments for TNE NDMM include Rd plus bortezomib (RVd) and daratumumab plus VMP (VMP þ D), daratumumab plus lenalidomide and dexamethasone (D þ Rd). Relative efficacy of these treatments was compared using a network meta-analysis. Eight trials identified by a systematic literature review were included in the primary analysis; hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were used. Rd was superior to other MP-based regimens for OS and PFS. There was strong evidence that, compared with Rd, both D þ Rd and RVd improved PFS (HR 0.57; 95% credible interval (CrI) 0.43, 0.73 and HR 0.72; 95% CrI 0.56, 0.91, respectively). However, there was strong evidence only for RVd in respect to OS (HR 0.72; 95% CrI 0.52, 0.96).

Treatment Regimens for Transplant-Ineligible Patients With Newly Diagnosed Multiple Myeloma: A Systematic Literature Review and Network Meta-analysis

“…A We found that both daratumumab-containing regimens evaluated (D-Rd and D-VMP) and VRd consistently had better PFS than Rd continuous; this finding was also seen in the simplified network of comparators relevant for Europe despite the different SOC options. These results are consistent with those of previous NMAs, including Cao et al [9], Ramasamy et al [13], and Xu et al [12] (D-Rd versus Rd PFS HRs, 0.57, 0.57, and 0.55, respectively). Cao et al also observed an advantage for D-VMP versus Rd (PFS HR, 0.59) [9], whereas the other studies were favourable but with different point estimators (PFS HRs, 0.73 and 0.71, respectively) [12,13].…”

“…These results are consistent with those of previous NMAs, including Cao et al [9], Ramasamy et al [13], and Xu et al [12] (D-Rd versus Rd PFS HRs, 0.57, 0.57, and 0.55, respectively). Cao et al also observed an advantage for D-VMP versus Rd (PFS HR, 0.59) [9], whereas the other studies were favourable but with different point estimators (PFS HRs, 0.73 and 0.71, respectively) [12,13]. This divergence in benefit is potentially attributable to the different data cut-offs for ALCYONE and VISTA used in the analyses.…”

“…In addition, since Cao et al [9] evaluated the full ITT population from the SWOG S0777 trial, their results may not accurately reflect the more vulnerable TIE patients. Ramasamy et al [13] performed a sensitivity analysis including ageadjusted data from SWOG S0777 that demonstrated results similar to their primary analysis.…”

“…Previous NMAs performed in this setting since 2019 have identified VRd, daratumumab in combination with VMP (D-VMP), and daratumumab in combination with Rd (D-Rd) as the most effective regimens in terms of progressionfree survival (PFS) and/or overall survival (OS) [8][9][10][11][12][13][14][15]. The results from these analyses also emphasize the benefits obtained from the use of triplet or quadruplet regimens.…”

Lenalidomide, bortezomib and dexamethasone induction therapy for the treatment of newly diagnosed multiple myeloma: a practical review

“…Specifically, RVD Lite demonstrated a VGPR rate of 66% and a median PFS of 41.9 months, which is comparable to 41 months in the updated analysis of the SWOG S0777 study 3,19 . A recent network meta‐analysis simultaneously assessing the comparative efficacy of several treatment options by direct and indirect comparisons showed that RVd was the only therapy with evidence of superiority over Rd in terms of OS 31 . Table 1 provides a summary of different induction regimens in the transplant‐ineligible patient.…”