Background: The standard of care for patients with monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) consists of watchful waiting until progression to clinically manifest multiple myeloma. While an increasing number of clinical trials are exploring the premise that early intervention in this MGUS/SMM patient population will prevent progression to multiple myeloma, little is known about how patients might balance the risks against potential benefits of early intervention.

Methods: To quantify preference for attributes of intervention in individuals with MGUS and SMM, we developed an online conjoint instrument with four attributes that we identified as being salient to clinical decision making: prevention of multiple myeloma, monthly cost, inconvenience, and risk of long-term side effects. We recruited individuals from two nationwide prospective cohorts to take the online instrument. To be eligible to participate, participants had to be age 18 or older, have a diagnosis of MGUS or SMM, and have no concurrent malignancy requiring active therapy. Logistic regression models were used to investigate the attributes that drive decisions of early treatment. In addition, we used a latent profile analysis to investigate latent classes defined by patient choices and assess patient characteristics that predict class membership.

Results: Participants (n=272) were 43% male, with a mean age of 64.1 (SD: 9.7) years. Logistic regression models suggest a strong preference for choosing interventions based on a higher likelihood of multiple myeloma prevention (odds ratio [OR] per 10% change:1.86, 95% confidence interval [CI]: 1.72, 2.00) and avoidance of side effects (OR: 0.10, 95%CI: 0.08, 0.13). Latent profile analysis identified three latent profiles: the first profile defines individuals who predominantly value avoidance of side effects, the second profile characterizes individuals who value keeping costs low, and the third profile of individuals values multiple myeloma prevention above other attributes. Mean age was similar across latent profiles. A higher proportion of individuals in profile two (group prioritizing cost) did not complete college and had a household income of less than $100,000. A similar proportion of individuals with SMM prioritized avoiding side effects as they did multiple myeloma risk reduction.

Conclusions: Overall, we found that low side effects and prevention of multiple myeloma are desirable intervention attributes in patients with MGUS and SMM. The prioritization of myeloma prevention vs low side effect profile was not perfectly coupled with an individual's disease burden. These findings reinforce the notion that a “one size fits all” approach to prevention and interception of multiple myeloma may not be suitable for all patients, and thus a diverse interventional portfolio may be needed to reach broad populations of patients with precursor conditions to multiple myeloma.

Marinac:Exact Sciences: Membership on an entity's Board of Directors or advisory committees. Ghobrial:Menarini Silicon Biosystems: Consultancy, Honoraria; The Binding Site: Consultancy; Pfizer: Consultancy, Honoraria; 10x Genomics: Honoraria; Regeneron: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Amgen: Consultancy; GlaxoSmithKline: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Disc Medicine: Other: Spouse is Chief Medical Officer and holds equity in the company; Vor Biopharma: Ended employment in the past 24 months, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Adaptive: Honoraria; Huron Consulting: Consultancy; Aptitude Health: Consultancy; Window Therapeutics: Consultancy; Oncopeptides: Consultancy. O'Donnell:Sanofi: Honoraria; BMS: Honoraria; Takeda: Honoraria; Janssen: Honoraria. Nadeem:GSK: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; GPCR Therapeutics: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

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