Practice Patterns in Newly Diagnosed Multiple Myeloma in the Prospective Observational Commpass Trial

Introduction:The management of multiple myeloma has become increasingly complex, given late age of onset, underlying co-morbidities, plethora of drugs, and variable clinical presentation and natural history. Practice patterns likely vary based on practice type, physician experience, and geographic distributions. The Multiple Myeloma Research Foundation's (MMRF) CoMMpass Trial (Relating Clinical Outcomes in Multiple Myeloma to Personal Assessment of Genetic Profile) is a prospective, longitudinal, observation trial in NDMM with the primary goal of correlating patient data and response with molecular profiles. Here, we evaluate practice patterns in NDMM the CoMMpass Trial based on staging, high-risk features, and demographics.

Methods: Clinical data were derived from MMRF's CoMMpass IA8, accessed in late July 2016 on https://research.themmrf.org/rp/explore. Independent categorical variables analyzed include International Staging System (ISS), Revised-ISS (R-ISS), LDH (normal vs. above upper limit of normal), Fluorescence-In-Situ Hybridization (FISH) (standard vs. high risk (t(4;14), t(14;16), t(14:20), del17p)), race, performance status (PS) (0-1, 2, 3-4), age (>65, 65-75, 76-80, >80 years), and gender. Dependent variables include use of doublets vs. triplets, the use of triplets using combined immunomodulatory/proteosome inhibition (IMID/PI), receiving or not receiving an autologous stem cell transplantation (ASCT), and timing of transplant (<10 vs. >10 months). For high-risk MM, defined as ISS 3, R-ISS 3, elevated LDH, or high risk FISH, patients receiving doublet therapy without an autologous stem cell transplantation were further analyzed for performance status and age. Descriptive statistics were used. Chi-square testing was used to compare variables, using STATA v14.1.

Results: Data on 921 patients has been released and was reviewed. Although men and women had similar upfront therapy, including the use of triplet (57% vs. 61%, p=0.483) and IMID/PI combinations (56% vs. 62%, p=0.181), women were more likely to have an ASCT (44% vs. 34%, p=0.002). When compared to European Americans (EA), African-Americans (AA) were less likely to receive triplets (47% vs. 61%, p=0.004), IMID/PI combination (55% vs. 59%, p=0.001), and ASCT (30% vs. 40%, p=0.034). Patients with high-risk disease were not more likely to be treated more aggressively. Patients with ISS Stage 3 disease were less likely to receive triplets (50% vs. 64%, p=0.002), IMID/PI combinations (51% vs. 66%, p=0.001), or an ASCT (26% vs. 48%, p=<10^-3). When comparing standard-risk MM, as defined by LDH or FISH, high-risk patients were not more likely to receive triplet therapy or ASCT. Performance status did not correlate triplet use, but lower rates of IMID/PI combinations and ASCT were noted in those with worse PS.

We subsequently reviewed patients with high-risk features who were treated with doublet therapy and without ASCT, specifically looking performance status and age. Of those with elevated LDH, 12 (46%) were younger than 65 years and 12 (46%) had PS<1. Of those with high risk FISH, 20 (49%) were younger than 65 years and 37 (76%) had PS<1. Of those with ISS 3, 24 (26%) were younger than 65 years and 49 (56%) had PS<1. Of those with R-ISS 3, 12 (44%) were younger than 65 years and 17 (63%) had PS<1.

Conclusions: The MMRF CoMMpass trial allowed assessment of practice patterns in the United States both inside and outside of academic medical centers. AA appear to be treated less aggressively, possibly explaining shorter survival despite more favorable cytogenetics. Second, high-risk disease does not appear to be treated more aggressively, even in younger patients with excellent performance status. This presented data must be interpreted with caution since this trial does not capture the treating physician's decision-making, nor survival data.