MM-431: A Comparison Between Daratumumab and Non-Daratumumab-Based Salvage Regimens Used at First Relapse Post-Lenalidomide Maintenance in Multiple Myeloma

Context Lenalidomide maintenance therapy after autologous stem cell transplantation (ASCT) is standard of care for patients with multiple myeloma (MM). However, most patients relapse, and the optimal choice of therapy at first-relapse post-lenalidomide maintenance is not established. Objective To compare the efficacy of salvage therapies at first relapse post-lenalidomide maintenance. Design Retrospective study of consecutive patients with MM seen at Mayo Clinic, Rochester between 1/1/2005–12/31/2016. Setting Tertiary referral center. Patients or Other Participants Two hundred thirteen patients treated with lenalidomide/lenalidomide-dexamethasone maintenance post-ASCT were screened; 136 patients experienced a first relapse. One hundred eighteen patients receiving salvage therapy were included in subsequent analyses. Interventions N/A Main Outcomes Measures The main outcome measure was second progression-free survival (2nd PFS), which was calculated from the start of therapy at first relapse after maintenance until therapy discontinuation. Results The median follow-up was 5.4 (95% CI: 4.9, 5.9) years from diagnosis. The median 2nd PFS was significantly longer in patients treated with daratumumab-based regimens [18.4 (95% CI: 10.9, 25.9) months; n=32] versus patients without daratumumab [8.9 (95% CI: 5.5, 12.3) months; n=86; p=0.006]. Adjusting for age, ISS stage 3, cytogenetic risk, Rd maintenance, and lenalidomide refractoriness at salvage, daratumumab-based therapy was associated with a significantly improved PFS [hazard ratio 0.31 (95% CI: 0.16, 0.61; p=0.001)]. The median 2nd PFS was superior in daratumumab + IMiD (n=16) compared to daratumumab + PI (n=15) [NR versus 1 yr (95% CI: 0.5, 1.5), respectively; p=0.004]. In patients not receiving daratumumab, median 2nd PFS was comparable between PI-based combinations [9.2 (95% CI: 6.6, 11.7) months; n=44], IMiD-based combinations [6.7 (95% CI: 0.82, 12.6) months; n=18; p=0.7], or PI + IMiD-based combinations [11.2 (95% CI: 0, 28.4 months; n=24; p=0.17]. Without daratumumab, there was also no significant difference in median 2nd PFS between patients who received lenalidomide-based combinations [6.7 (95% CI: 0, 15.4) months] compared with pomalidomide-based regimens [20.1 (95% CI: 0, 41.4) months; p=0.5]. Conclusions Daratumumab-based therapies at relapse are associated with improvement in 2nd PFS, and daratumumab-IMiD combination was superior to daratumumab-bortezomib combination. Without daratumumab, there was no significant difference between doublet versus triplet therapies, IMiD-versus PI-based regimens or lenalidomide versus pomalidomide-based combinations.