Grant Number:	1U01CA319115-01 Interpret this number
Primary Investigator:	Chang, Su-Hsin
Organization:	Washington University
Project Title:	Comparative Modeling of Multiple Myeloma Prevention, Early Detection and Treatment Interventions
Fiscal Year:	2026

PROJECT SUMMARY/ABSTRACT Multiple myeloma (MM) is a common and lethal hematologic malignancy. Despite advances in treatment, MM remains incurable. Furthermore, MM management is the most costly among all cancer sites, primarily due to expensive multidrug regimens driven by rapidly emerging industry-sponsored trials that show promising results. In 2021, the MM Working Group (MMWG) was funded to develop natural history models of MM to fill a gap in the cancer sites covered by CISNET. While CISNET has used modeling to set policy goals and design interventions, these efforts have thus far been solely focused on solid tumors. Given that MM is the most burdensome liquid tumor, continued support is essential for MMWG to sustain their modeling efforts and further advance MM prevention and control. This U01 initiative will involve two modeling groups and expand the three independent, CISNET-standard natural history of MM models to conduct comparative modeling, coordinated by the coordinating center. MMWG will 1): study incidence trends of MM and its premalignant conditions. MGUS and smoldering MM (SMM), addressing critical questions like "To what extent has the rising prevalence of obesity contributed to the incidence of early-onset MM?" and “Can the updated SLiM-CRAB criteria improve MM survival?” 2): Evaluate novel strategies for managing SMM, including treatments for high- risk SMM and the use of GLP1-RA for non-high-risk SMM; 3) assess novel treatment regimens in MM; and 4) conduct participatory modeling to enhance MM care accessibility and affordability. MMWG is well-prepared to study these aims. First, MMWG has quantified the contribution of obesity on MM progression and estimated the associations of GLP1-RA use with MM progression. Second, MMWG has led studies on SMM using newly released registry data and leveraged NLP to identify SMM within a nationwide EHR system. Third, in a pilot community-based study, MMWG identified insurance, rural, and socioeconomic status as top barriers to MM care. The proposed U01 will address seven of the nine priority areas outlined in the RFA. It is significant in its capability to 1) expand CISNET-standard comparative modeling for MM, a cancer lacking such modeling to inform prevention and control policies, unlike those solid tumors already with such modeling to guide interventions and policies; 2) provide evidence-based evaluation even before the implementation of costly clinical trials; 3) explore novel interventions/treatments at various stages of MM; and 4) assess the value of novel therapies, thereby informing a shift in current clinical practice of SMM and MM management. The proposed U01 is novel in 1) incorporating the challenging SMM stage, enabling analyses across the entire spectrum of MM prevention and care continuum; 2) utilizing both comparative and participatory modeling to inform MM prevention and control strategies; and 3) applying novel calibration methods adapted for MM modeling. MMWG has demonstrated remarkable productivity within CISNET and is uniquely positioned to continue making impactful advances in MM prevention and control.





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