Evolving Areas of Consensus and Disagreement Among Experts in Treatment of Patients with Multiple Myeloma (MM)
Authors: Rosenthal Kristen M , Ghobrial Irene M. , Huff Carol Ann , Lonial Sagar , Raje Noopur , Obholz Kevin L , Kumar Shaji K. 
Published: October 2019

Abstract
From 2013-2017, numerous new approvals and expanded indications have dramatically changed the treatment (tx) landscape for MM. Since that time, experienced MM physicians from leading academic institutions and cancer centers (experts) have annually updated and contributed tx recommendations for an online decision support tool designed to provide healthcare providers (HCPs) with patient-specific tx guidance. This MM tool is freely available online at www.clinicaloptions.com/myelomatool and HCPs can use the tool to enter details of a patient case, indicate their intended tx plan, and then expert tx recommendations for that case are provided.
Methods
This study includes analysis of tx recommendations from 5 MM experts for 270 unique MM case scenarios made during development of the 2018 update to this tool. We also aim to compare the evolving tx recommendations among the experts over time, from 2013-2017, and to determine practice patterns of HCPs using the tool over the same time span.
Results
Based on analysis of these annually updated MM tools, consensus (≥ 3 of 5 experts choosing the same tx for the same case) among experts has been increasing for induction tx since 2013. In ASCT-eligible patients with no specific comorbidities, experts recommended bortezomib/lenalidomide/dexamethasone (VRd) in 100% and 90% of tool cases in 2018 and 2017, respectively, which increased from 65% to 75% consensus in 2013-2015. In previous analyses, the percentage of HCPs using VRd has also increased, albeit more slowly than with experts. In 2017, 42% of HCPs indicated that they are using VRd as induction in this setting compared with 22% in 2015-2016 and 9% in 2014-2015. For ASCT-ineligible patients with ECOG > 2 but no specific comorbidities, all 5 experts recommend triplet therapy for all cases regardless of risk in 2018, but in 2017, 3 of 5 recommended triplet therapy and 2 of 5 recommended doublets for normal-risk disease.
Expert recommendations for induction change, however, based on specific patient comorbidities. For patients with peripheral neuropathy, 4 of 5 experts recommended carfilzomib/lenalidomide/dexamethasone instead of VRd. For patients with renal insufficiency, 4 of 5 experts recommended bortezomib/cyclophosphamide/dexamethasone. For patients with cardiac dysfunction, all 5 experts continue to recommend VRd for patients with ECOG ≤ 2 while 2 of 5 change from VRd to Rd for patients with ECOG > 2.
For patients who achieve VGPR or better to induction, all 5 experts recommend lenalidomide maintenance for standard risk disease. But for patients with high risk disease who achieve VGPR or better to induction, 3 of 5 experts recommend bortezomib/lenalidomide combination maintenance therapy regardless of induction regimen, 1 expert recommends single-agent bortezomib regardless of induction regimen, and 1 expert recommends bortezomib after a PI-based induction regimen or lenalidomide for an IMiD or IMiD/PI-based induction regimen.
In the 2018 tool update, the number of R/R case scenarios with 100% expert consensus increased over previous years: 20% of cases had all 5 experts agreeing on tx vs 12% in 2017. In addition, 29% of cases had 3 of 5 experts agreeing and 8% had 2 pairs of experts agreeing in 2018 vs none with 3 of 5 experts agreeing and 21% with 2 pairs of experts agreeing in 2017. In 2018, experts recommended daratumumab/pomalidomide/dexamethasone all cases with 100% consensus, which comprises patients who are refractory to multiple agents including lenalidomide, bortezomib, and/or carfilzomib. Overall, 23 different regimens were recommended for R/R MM; and additional majority expert consensus included daratumumab/lenalidomide/dexamethasone, daratumumab/carfilzomib/dexamethasone, and carfilzomib/pomalidomide/dexamethasone (Table 1).
Conclusions
Practice patterns are changing rapidly and are more complex, particularly in the R/R setting, in response to the evolving tx landscape for MM. This analysis highlights several areas of expert consensus, but disparities remain for select cases. The newest approved therapies continue to have a strong impact on experts' recommendations as they have been fully integrated into their tx approaches. These analyses provide a real-time assessment of changing tx patterns among experts as well as HCPs.
We will present analyses of cases entered in the 2018 online tool by HCPs and detailed comparisons of expert and the intended tx of clinicians using the tool.

Disclosures
Ghobrial: Takeda: Consultancy; Janssen: Consultancy; Celgene: Consultancy; BMS: Consultancy. Lonial:Amgen: Research Funding. Raje:Research to Practice: Honoraria; Takeda: Consultancy; AstraZeneca: Research Funding; Celgene: Consultancy; BMS: Consultancy; Merck: Consultancy; Janssen: Consultancy; Amgen Inc.: Consultancy; Medscape: Honoraria. Kumar:Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding.