Impact of 1q gains on treatment outcomes of patients with newly diagnosed multiple myeloma in a real-world Swedish population receiving modern treatment.

BACKGROUND: Amplification of 1q (amp(1q); ≥4 1q copies) has repeatedly been reported to predict a worse outcome in multiple myeloma (MM), whereas the impact of gain of 1q (gain(1q); three 1q copies) is less clear. METHODS: We investigated survival of MM in relation to amp(1q) and gain(1q) by retrospectively analysing 346 consecutively newly diagnosed MM (NDMM) patients. Of these, 62 (18%) had amp(1q), 97 (28%) gain(1q) and 187 (54%) a normal number of 1q copies (no1q). RESULTS: The patients with amp(1q) had a shorter median progression-free survival than those with gain(1q) or no(1q) (13.1 months, 95% confidence interval [CI] 8.2-18.1 months vs. 36.1 months, 95% CI 23.1-49.1 months vs. 25.4 months, 95% CI 19.8-31.1 months, p = .005). The 3-year overall survival (OS) was 56% for amp(1q), 76% for gain(1q) and 80% for no1q (p = .003). In the multivariate analysis, the presence of amp(1q) was independently associated with a shorter OS (hazard ratio 1.99, 95% CI 1.03-3.82, p = .039), whereas gain(1q) had no negative effect on survival. CONCLUSION: Our results thus suggest that amp(1q) should be considered a high-risk abnormality in NDMM and that new treatment strategies should be explored to mitigate its negative effect on survival.

Ixazomib, Lenalidomide, and Dexamethasone (IRD) Treatment with Cytogenetic Risk-Based Maintenance in Transplant-Eligible Myeloma: A Phase 2 Multicenter Study by the Nordic Myeloma Study Group.

Scarce data exist on double maintenance in transplant-eligible high-risk (HR) newly diagnosed multiple myeloma (NDMM) patients. This prospective phase 2 study enrolled 120 transplant-eligible NDMM patients. The treatment consisted of four cycles of ixazomib-lenalidomide-dexamethasone (IRD) induction plus autologous stem cell transplantation followed by IRD consolidation and cytogenetic risk-based maintenance therapy with lenalidomide + ixazomib (IR) for HR patients and lenalidomide (R) alone for NHR patients. The main endpoint of the study was undetectable minimal residual disease (MRD) with sensitivity of <10-5 by flow cytometry at any time, and other endpoints were progression-free survival (PFS) and overall survival (OS). We present the preplanned analysis after the last patient has been two years on maintenance. At any time during protocol treatment, 28% (34/120) had MRD < 10-5 at least once. At two years on maintenance, 66% of the patients in the HR group and 76% in the NHR group were progression-free (p = 0.395) and 36% (43/120) were CR or better, of which 42% (18/43) had undetectable flow MRD <10-5. Altogether 95% of the patients with sustained MRD <10-5, 82% of the patients who turned MRD-positive, and 61% of those with positive MRD had no disease progression at two years on maintenance (p < 0.001). To conclude, prolonged maintenance with all-oral ixazomib plus lenalidomide might improve PFS in HR patients.