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

Abstract

BackgroundIxazomib-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.MethodsNinety 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.ResultsThe 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.ConclusionsIxazomib–thalidomide–dexamethasone followed by ixazomib maintenance therapy is active and well tolerated in patients with RRMM.Trial registration numberNCT02410694

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

“…Also, one should keep in mind that the EORTC instruments do not specifically capture satisfaction with sexual function, an item which is of importance to a proportion of patients with excellent control of their disease [31,32]. Furthermore, other instruments such as the FACT-MM PRO [33] or the FACT-G could have been used, but we selected the EORTC QLQ C30 and QOL-MY20 questionnaire for this study as the latter tools have uniformly been used in all of the recent MM trials [9,12,13,28,29,23] with QoL assessments, a fact which facilitates comparison of results.…”

“…In addition, as information regarding possible differences in QoL between myeloma patients and the general population is not available, we compared several dimensions of QoL between our patients with RRMM with that observed in the normal population of similar age from the same area. [13]. The trial protocol was approved by each study site's Independent Ethics Committee or Institutional Review Board, and the study was conducted in accordance with the Declaration of Helsinki.…”

Design and discovery of boronic acid drugs

“…Its mechanism of action was found to be nearly identical to that of Bortezomib, yet it was found to be more potent, less prone to inducing adverse side effects (higher specificity), and even to treat certain patients whose tumours have developed resistance to Bortezomib [34]. Although approved, Ixazomib is also under clinical trials as part of combination therapies to treat multiple myeloma [34,35].…”

A phase II trial of continuous ixazomib, thalidomide and dexamethasone for relapsed and/or refractory multiple myeloma: the Australasian Myeloma Research Consortium (AMaRC) 16‐02 trial

“…14,15 IXA has been evaluated in both newly diagnosed MM and relapsed and/or refractory MM (RRMM), as well as for maintenance therapy following autologous stem cell transplant (ASCT), both as a single agent and in combination with other anti-MM therapies, where it has been shown to improve progression-free survival (PFS). [16][17][18][19][20] IXA has been proven to be efficacious and tolerable when combined with immunomodulatory drugs (IMIDs), most notably in combination with lenalidomide (LEN). The TOURMALINE-MM1 trial (ClinicalTrials.gov Identifier: NCT01564537) demonstrated an improvement in PFS when IXA was added to LEN and dexamethasone (DEX) (Rd) when compared to Rd alone (20Á6 vs. 14Á7 months) in patients with one to three prior lines of therapy.…”