Reduced alpha diversity of the oral microbiome correlates with short progression-free survival in patients with relapsed/refractory multiple myeloma treated with ixazomib-based therapy (AGMT MM 1, phase II trial).

Alterations in the human microbiome have been linked to several malignant diseases. Here, we investigated the oral microbiome of 79 patients with relapsed/refractory multiple myeloma (MM) treated with ixazomib-thalidomide-dexamethasone. Increased alpha diversity (Shannon index) at the phylum level was associated with longer progression-free survival (PFS) (10.2 vs 8.5 months, P = .04), particularly in patients with very long (>75% quartile) PFS . Additionally, alpha diversity was lower in patients with progressive disease (P < .05). These findings suggest an interrelationship between the oral microbiome and outcome in patients with MM and encourage a novel direction for diagnostic and/or therapeutic strategies.

Quality of life in patients with relapsed/refractory multiple myeloma during ixazomib-thalidomide-dexamethasone induction and ixazomib maintenance therapy and comparison to the general population.

This trial evaluated quality of life (QoL) using the EORTC QLQ-C30 and the EORTC QLQ-MY20 instruments in 90 patients with relapsed/refractory multiple myeloma during induction and maintenance therapy with eight cycles of ixazomib-thalidomide-dexamethasone, followed by 12 months of ixazomib maintenance therapy. When patient's baseline QoL was compared with data of the general population, a significant impairment in health-related QoL, physical, role, and social functioning and several other dimensions, as well as more pain and fatigue, was noted. Induction therapy resulted in significant improvement of pain and worsening of neuropathy, with no significant variation of other parameters. During maintenance treatment, scores for most dimensions including health-related QoL, physical functioning and pain, improved, while for neuropathy no improvement was observed. Time to deterioration (≥10 score points) of health-related QoL, physical functioning, pain, and neuropathy was distinctly shorter than time to progression. Health-related QoL and physical functioning at baseline correlated with overall survival.

Ixazomib-Thalidomide-Dexamethasone for induction therapy followed by Ixazomib maintenance treatment in patients with relapsed/refractory multiple myeloma.

BACKGROUND: Ixazomib-revlimid-dexamethason showed significant activity in relapsed/refractory multiple myeloma (RRMM). Here, we evaluate ixazomib in combination with thalidomide and dexamethasone for induction treatment followed by ixazomib maintenance therapy in RRMM patients. METHODS: Ninety patients have been included. Ixazomib-thalidomide-dexamethasone (4 mg, day 1, 8, 15; 100 mg daily; and 40 mg weekly) was scheduled for eight cycles followed by maintenance with ixazomib for one year. RESULTS: The overall response rate was 51.1%, 23.3% achieved CR or VGPR and 10% MR resulting in a clinical benefit rate of 61.1%. In patients completing ≥2 cycles, the rates were 60.5%, 27.6% and 68.4%, respectively. Median progression-free survival (PFS) was 8.5 months in all, and 9.4 months in those completing ≥2 cycles. Response rates, PFS and overall survival (OS) were similar in patients with and without t(4;14) and/or del(17p), but PFS and OS was significantly shorter in patients with gain of 1q21. Multivariate regression analysis revealed gain of 1q21 as the most important factor associated with OS. Ixazomib maintenance resulted in an upgrade in the depth of response in 12.4% of patients. Grade 3/4 toxicities were relatively rare. CONCLUSIONS: Ixazomib-thalidomide-dexamethasone followed by ixazomib maintenance therapy is active and well tolerated in patients with RRMM. TRIAL REGISTRATION NUMBER: NCT02410694.