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The MM Hub is pleased to share research findings from the 59th American Society of Hematology (ASH) Annual Meeting in Atlanta, Georgia. On Monday 11 December 2017, an evening oral abstract session took place: Session 653. Myeloma: Therapy, Excluding Transplantation II. This session was moderated by Kenneth H. Shain from the Moffit Cancer Center, Tampa, FL and Elisabet E. Manasanch from the MD Anderson Cancer Center, Texas. Several of the talks in this session covered treatment options for Newly Diagnosed Multiple Myeloma (NDMM) patients and are summarized below. The data is based on that presented at the live sessions and may supersede that in the pre-published abstracts.
The first talk in this session was delivered by Sara Bringhen from University of Torino, Torino, Italy, in which she presented updated data from the phase III EMN01 study. Continuous lenalidomide, induction and maintenance therapy has shown improvement in progression-free (PFS) survival for elderly, non-transplant eligible patients. Prior studies including MM-015 trial and the FIRST trial have both demonstrated this benefit. The aims of the current study were to assess the impact on outcomes for non-transplant eligible MM patients, comparing triplet versus doublet induction and single versus 2 drug maintenance therapy.
Professor Bringhen concluded that alkylator-based 3-drug regimens have a higher rate of grade 3/4 toxicities, and may be best suited for fit elderly patients. The added risk of toxicity from alkylator therapies does not offer significant improvements in PFS in this cohort of patients, based on the data presented. Mature data for OS is not available at this time.
Meletio Dimopoulos of National and Kapodistrian University of Athens, Greece presented an analysis of ixazomib maintenance therapy in NDMM patients not undergoing autologous stem cell transplant (ASCT). This summary of four studies prescribed standard MM therapy combinations of lenalidomide-dexamethasone (Rd), melphalan-prednisone (MP) or cyclophosphamide-dexamethasone (Cd) in addition to ixazomib induction and continued maintenance therapy. Ixazomib, the first oral proteasome inhibitor, was dosed once or twice weekly. This study examined the impact on progression-free survival (PFS) and overall survival (OS) with long-term ixazomib maintenance.
This analysis demonstrated good outcomes for NDMM patients with prolonged ixazomib maintenance therapy. Ixazomib provided good results in terms of response rate and survival, with an acceptable AE profile. Professor Dimopoulos concluded that his data provides support for the ongoing phase III trial of the safety of ixazomib in MM patients not undergoing ASCT.
The last talk in this series was given by Anjali Mookerjee from AIIMS New Delhi, India, who presented data from a phase III trial to determine differences in efficacy for a bortezomib triplet versus doublet therapy in NDMM patients. The triplet regimen was bortezomib-dexamethasone-lenalidomide (VRD) compared to lenalidomide-dexamethasone (Rd). Prior trials have compared Rd to thalidomide-dexamethasone and yielded no significant difference in clinical outcomes.
Patients included in this study had not received prior treatment with immunomodulatory agents or proteasome inhibitors, could not have diabetes, psychiatric disorders, active infections or be pregnant. The evaluation was after 4 cycles, each of 28 days in length.
This study adding bortezomib to induction therapy in NDMM patients demonstrated no difference in survival or disease progression outcomes and is consistent with other historical studies. The AE profile was tolerable, but a higher rate of VRD patients discontinued therapy due to secondary to toxicity.
References
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What is the most significant limitation you have identified when using lenalidomide or pomalidomide for the treatment of patients with multiple myeloma?