Short progression-free survival predicts for poor overall survival in older patients with multiple myeloma treated upfront with novel agent-based therapy

Objectives: To assess the importance of the quality of response and of early relapse in unselected elderly patients with myeloma treated upfront with novel agents. Methods: We analyzed 135 unselected transplant-ineligible patients older than 65 yr who were treated upfront with novel agent-based regimens in a single center. Results: On intent to treat, 81% of patients achieved a response (28% sCR/CR, 23% VGPR, and 30% PR). Median progression-free survival (PFS) for patients who achieved sCR/CR was 31 vs. 20 months for VGPR and 23 months for PR (P = 0.048). Median overall survival (OS) for patients with sCR/CR was 62 months, 53 months for VGPR and 38 months for patients with PR (P = 0.028). Early relapse (PFS < 12 months) was more common in patients with PR (39% vs. 21% for VGPR vs. 3% for sCR/CR). Patients who relapsed or progressed < 12 months from initiation of treatment had a median OS of 15.4 months compared with 53 months (P < 0.001) for patients who had a PFS > 12 months despite the fact that after relapse or progression most patients were treated again with novel agents. In multivariate analysis, short PFS was the most significant adverse prognostic factor affecting OS, associated with a 7.25-fold (P < 0.0001) increase in the risk of death. Conclusion: In newly diagnosed patients over 65 yr, treated upfront with novel agents achievement of CR and a PFS 12 months is associated with improved outcome. Patients who fail to respond or experience early relapse after primary therapy with novel agent-based regimens should be encouraged to participate in clinical trials of novel agents and combinations.