Impact of Treatment Sequencing on Overall Survival in Patients with Transplant-Ineligible Newly Diagnosed Myeloma

Abstract

Background Because patients with newly diagnosed multiple myeloma (NDMM) do not always receive any treatment beyond first-line (1L) therapy, it is imperative that patients receive the best treatment in the 1L setting. However, the optimal initial treatment remains to be identified. We performed a clinical simulation to assess potential outcomes with different treatment sequences. Patients and Methods We used a partitioned survival model to compare overall survival (OS) with (1) daratumumab, lenalidomide, and dexamethasone (D-Rd) in 1L followed by a pomalidomide- or carfilzomib-based regimen in second line (2L) versus (2) bortezomib, lenalidomide, and dexamethasone (VRd) in 1L followed by a daratumumab-based regimen in 2L versus (3) lenalidomide and dexamethasone (Rd) in 1L followed by a daratumumab-based regimen in 2L. Probabilities of transition between health states (1L, 2L+, and death) were based on published clinical data and real-world data from the Flatiron Health database. The proportion of patients discontinuing treatment after 1L (attrition rates) in the base case was estimated with a binomial logistic model using data from the MAIA trial. Results Using D-Rd in 1L conferred a longer median OS compared with delaying daratumumab-based regimens until 2L after VRd or Rd, respectively (8.9 [95% CrI 7.58-10.42] vs. 6.92 [5.92-8.33] or 5.75 [4.50-7.25] years). Results of scenario analyses were consistent with the base case. Conclusion Our simulation, which incorporates clinically representative treatments and attrition rates, supports the use of D-Rd as initial therapy, rather than delaying the use of daratumumab until later lines of therapy, in patients with transplant-ineligible NDMM.

New Strategies for the Treatment of Older Myeloma Patients

“…Moreover, a higher probability of being alive at 5, 10, and 15 years was associated with first-line D-Rd, as compared with first-line VRd or Rd. These data suggest the importance of first-line therapy and confirm that achieving the longest possible PFS in first-line therapy drives survival outcomes [53].…”

Daratumumab Treatment for “Truly Frail” Elderly Myeloma Patients

“…According to Fonseca et al, it has been demonstrated that a DARA-containing regimen applied as the initial treatment leads to a longer median OS compared to introducing a DARA-containing regimen as a secondary treatment following VRd or Rd [ 46 ]. In the absence of head-to-head trials comparing D-Rd to VRd or to BTZ and DEX (Vd), the PEGASUS study compared PFS in patients treated with D-Rd in the MAIA trial and patients treated with common standard-of-care regimens from the Flatiron Health electronic health record-derived deidentified database [ 47 ].…”

Mezigdomide—A Novel Cereblon E3 Ligase Modulator under Investigation in Relapsed/Refractory Multiple Myeloma

“…Over the past 40 years, multiple myeloma (MM) has evolved from an acute disease with a median overall survival (OS) of only ~3–4 years [ 1 ] to become a chronic disease in which the median OS is now 7–10 years [ 2 , 3 ], and patients can require multiple lines of therapy over their disease course [ 4 , 5 , 6 , 7 ]. In the context of a global annual incidence of approximately 180,000 new cases [ 8 ], including more than 35,000 in the United States alone [ 9 ], and the continuing increase in survival rates [ 10 ], there is a growing population of patients requiring additional treatment options.…”