MM-CARE: Cardiovascular Risk Assessment in Adults With Multiple Myeloma

MM-CARE is a prospective, pragmatic, open-label, randomized pilot feasibility study evaluating two approaches to cardiovascular risk assessment for adults with multiple myeloma who are starting a new line of systemic therapy.

After informed consent, eligibility confirmation, and completion of baseline study assessments, participants who do not require urgent inpatient treatment will be randomized 1:1 to the oncology-embedded pathway or the primary care provider (PCP)-directed pathway. Randomization will be stratified according to whether the participant's PCP practices within the University of Vermont Health Network. Participants and clinicians will know the assigned pathway.

Participants assigned to the oncology-embedded pathway will receive a focused cardiovascular risk-assessment visit with an internal medicine clinician who works with the oncology team. The assessment may be conducted in person or by secure video and will include review of cardiovascular history, symptoms, family history, medications, vital signs, relevant laboratory and electrocardiogram results, physical activity, diet, tobacco use, and medication adherence. The clinician may provide counseling or recommend additional clinical evaluation, referrals, or medications based on the participant's individual needs. Clinical follow-up will occur at approximately Months 3, 6, and 12.

For participants assigned to the PCP-directed pathway, the study team will send the participant's PCP a structured letter within five business days after randomization. The letter will request a focused cardiovascular risk assessment and will include relevant clinical information and available laboratory and electrocardiogram results. The PCP will be asked to complete the assessment as soon as feasible, preferably within 30 days after treatment initiation and no later than six months after treatment initiation. The study team will track whether the assessment occurred and collect information about recommendations, medication changes, and referrals.

Participants who are hospitalized because of a multiple myeloma-related emergency and must begin a new line of therapy in the hospital will enter a separate nonrandomized urgent-treatment cohort. These participants will receive the oncology-embedded cardiovascular assessment during the qualifying hospitalization and will be analyzed separately from the randomized groups.

The study does not require a specific cardiovascular medicine, test, referral, diet, exercise plan, or change to multiple myeloma treatment. All clinical decisions will be made by the participant and the responsible clinicians. Multiple myeloma treatment may begin before or after the cardiovascular assessment and will not be delayed to complete study activities.

Study assessments will occur at baseline and approximately Months 3, 6, and 12. Participants will complete questionnaires about physical function, quality of life, physical activity, diet, the perceived helpfulness of the cardiovascular assessment, and whether they followed recommendations. The study team will also review relevant medical information and available results from blood tests and electrocardiograms performed as part of usual clinical care. Participants may separately agree to provide an additional 10 mL blood sample at each of these four time points for storage and future research.

Active study participation will continue through Month 12. At Month 24, the study team will conduct a medical-record review for cardiovascular events, hospitalizations, new cardiovascular diagnoses, deaths, and cardiovascular-related changes or interruptions to multiple myeloma treatment. No participant visit or additional procedure is required at Month 24.

The primary purpose of this pilot study is to evaluate whether the cardiovascular assessment pathways can be implemented and completed within the planned timeframe. The study is not designed or statistically powered to establish that one pathway produces better clinical outcomes than the other. Findings will be used to inform the design of a larger future study.

Inclusion criteria

• Confirmed diagnosis of multiple myeloma.
• Age 18 years or older.
• Preparing to begin a new line of systemic multiple myeloma treatment in the newly diagnosed or relapsed or refractory setting.
• Planned ongoing oncology care with anticipated clinical visits sufficient to coordinate study assessments at Months 3, 6, and 12.
• For participants eligible for randomization, an established primary care provider who can be identified at enrollment and contacted by the study team if the participant is assigned to the primary care provider-directed pathway.
• Ability to understand the study and willingness to provide written informed consent.

Exclusion criteria

• An acute cardiovascular condition requiring emergency evaluation or specialty cardiology management rather than routine cardiovascular risk assessment, as determined by the treating clinician.
• Any condition that, in the investigator's judgment, would prevent meaningful participation in the study intervention or required assessments.
• Hospitalization or an urgent need to begin multiple myeloma treatment is not an exclusion.

Participants meeting the urgent-treatment criteria may enroll in the separate nonrandomized urgent-treatment cohort.