Background: The expansion of genomic testing in multiple myeloma (MM) has focused largely on targeted assays (e.g., FISH, NGS), which fail to capture genome-wide complexity. Whole genome sequencing (WGS) of circulating tumor cells offers a less invasive path toward identifying structural variants, copy number changes, and alterations in therapeutic targets (e.g., BCMA, GPRC5D) that may provide unprecedented guidance for personalized treatment selection - treatments with the greatest potential for efficacy. However, patient readiness and perceived utility of WGS remain largely unexplored, particularly in precursor disease states.

Methods: A 14-item cross-sectional survey was administered through the HealthTree Foundation platform to a cohort of 480 patients diagnosed with MGUS, smoldering myeloma, or MM. The survey was developed by authors JRH, JMA, FA, and a clinical researcher familiar with WGS in myeloma and reviewed by the HealthTree Patient Advisory Board. IRB exemption determinations were granted by Sterling IRB. The survey assessed prior genetic testing, perceived importance of WGS, treatment decision confidence, and willingness to undergo WGS via blood or bone marrow. After reviewing a brief educational passage about WGS (framed as a behavioral intervention) participants re-rated its clinical utility. Results were stratified by MM (85%) vs. precursor condition (15%) status.

Results: The median participant age was 68 years (IQR: 61–72). Overall 56% were female, however precursor patients were more often female (72% vs. 53%, p=0.02). No differences in race (87% non-Hispanic White) or education (43% held graduate/professional degrees) were detected. Patients with precursor conditions had lower levels of caregiver support compared to those with multiple myeloma (MM), with only 46% reporting an at-home caregiver versus 71% among MM patients (p < 0.001). Additionally, a higher proportion of patients with precursor conditions reported inadequate caregiver support, defined as difficulty finding a caregiver, at 15%, compared to 4% among MM patients (p < 0.001). However there were no differences observed for being a caregiver to someone else (16%) or cohabitance - 79% lived with a spouse and 14% lived alone.

Despite presenting clinical severity differences, both MM and precursors groups reported uncertainty in treatment selection: 29% of MM and 52% of precursor patients felt “not very” or “not at all confident“ about which therapies might work best (p < 0.001), with only 21% of MM and 10% of precursor patients feeling “very confident.”

Interestingly, 60% of participants reported having little or no familiarity with WGS. However, 77% of MM patients reported previously being tested for FISH, NGS, or exome sequencing, compared to 59% of precursors (p<0.001). With a majority (57%) agreeing that MM patients have fewer tools than those with solid tumors for selecting targeted treatments. Although 74% believed their doctors valued genetic testing, only 62% of MM and 56% of precursor patients rated WGS as “extremely important” pre-intervention.

After a short educational passage describing WGS as a comprehensive tool for identifying mutations beyond current diagnostics, ratings of WGS importance rose sharply: 74% of MM and 83% of precursor patients now considered it “extremely important,” with the greatest increase seen in the precursor group (+18% vs. +21%, p < 0.05). Additionally, 95% of respondents were willing to undergo a blood-based WGS test, compared to 70% for bone marrow biopsy (p<0.001). Furthermore, participants showed a strong interest in participating in future WGS research, 82% of MM and especially among precursor patients (93%, p < 0.05).

Conclusions: Patients living with a plasma cell disorder show strong interest in WGS as a precision oncology tool, with their interest being reinforced after brief education about its importance in their care. Notably, despite having less prior exposure to genetic testing, precursor patients were more influenced by the educational prompt and more likely to opt into research, which suggests high responsiveness and unmet need at earlier disease stages. These findings support the development of blood-based WGS tools for multiple myeloma and emphasize the promise of genomic personalization, especially for patients in early stages of disease where uncertainty is greatest.

This content is only available as a PDF.
2025
Sign in via your Institution