Flott, Caitlin

Abstract Background: MM is the second most common hematologic malignancy, which despite significant therapeutic advancements, remains incurable. The complexity of MM and its intricate management creates substantial informational demands for patients navigating their care. Methods: A cross-sectional survey study (Mayo Clinic IRB # 25-004671) was conducted to assess MM patients’ awareness about disease basics. A voluntary English language survey (47 questions) encompassing multiple domains of patient MM awareness was administered (REDCap) via the patient EMR portal (Mayo Clinic) and MM support groups nationally. Responses were analyzed using descriptive and inferential statistics (R; Bluesky Statistics, V 10.3.4). Multiple model logistic regression was used for multivariate analysis using age (≤70 or >70 yrs), gender, education (high school or less vs bachelor's and above), income (≤$74999 vs ≥$75000) and insurance status (private vs public). Results: The survey was completed by 2353 patients (pts) with 2177 MM (83.4% active, 16.6% smoldering) and 176 MGUS. Among MM pts median age was 63 yrs with 52.5% males, 91.5% white and 95.7% non-Hispanic. 17.5% had a prior diagnosis of MGUS and 20.2% of smoldering MM prior to MM, and 79.5% were not aware of MM prior to their own diagnosis. Majority (77%) depended most on their doctors to gain MM information but 24.3% reported not having sufficient discussion about MM at diagnosis. 31.2% were not sure what type of MM they had, 22.9% could not correctly report the cell of MM origin (plasma cell), 40.6% did not receive MM stage information at diagnosis, 45.4% were either unsure or reported wrong risk factors for MM and 22% were unsure or mistaken about MM symptoms. Majority (62.9%) did not understand genetic risk categories of MM, 32.3% did not report adequate understanding of MM tests and 31.9% did not understand the difference between response and remission. 57.5% reported not understanding about MRD status and 57.1% never had MRD testing. Majority (86.8%) felt they got adequate opportunity to participate in treatment decisions but only 54.2% felt confident in managing MM with their current knowledge and 28.2% had not discussed their prognosis although 77.7% wanted to know about it. Majority (64.4%) felt they had knowledge gaps about MM and its management. Multivariate analysis showed that females were less likely (OR 0.67) while those with public insurance were more likely (OR 1.35) to report receiving adequate information at diagnosis. Older pts (OR 0.55), males (OR 0.43), with lower education (OR 0.5), lower income (OR 0.5) and public insurance (OR 0.72) were less likely to identify the cell of MM origin correctly. These same groups were significantly less likely to be aware of types of MM as well. Older pts (OR 0.73), with lower education (OR 0.6), lower income (OR 0.77) and public insurance (OR 0.76) were less likely to be aware of MM genetic risk categories. Females (OR 0.81), with lower education (OR 0.68) and lower income (OR 0.63) were less likely to understand MM lab tests. Females and those with lower income were significantly less likely to report receiving adequate information about treatment options. Females reported that they did not get adequate opportunities to participate in treatment decisions (OR 0.65). Older pts, and those with lower income, lower education or public insurance were less likely to understand minimal residual disease (MRD) and all these groups were less likely to have had MRD testing. Those with lower income (OR 0.75) and lesser education (OR 0.72) felt less confident in managing MM with current knowledge. Older pts, females and those with lesser education, lower income and public insurance were also significantly less likely to have discussed about MM prognosis. Conclusion: This study demonstrates substantial basic knowledge deficits integral to managing and prognosticating MM among patients. Patients from unfavorable sociodemographic-economic groups were more likely to have awareness gaps and report lack of information which is integral to having adequate understanding of MM being provided to them. These findings highlight the critical need for structured, comprehensive educational interventions that address fundamental disease concepts to empower pts, overcome healthcare disparities, and engage pts in shared decision-making.

Abstract Background: The phase II and III GRIFFIN and PERSEUS studies evaluated DVRd vs. VRd in NDMM pts that were transplant eligible (TE). These studies included consolidation (cons) and dual agent maintenance (maint) with dara and len (DR). Little is known about the efficacy of DVRd in RW practice including frequency of bor use, use of cons, use of DR maint, and subsequent treatment after progression (PD) on DVRd. We aim to evaluate the RW efficacy of NDMM pts treated with DVRd across the tri-site Mayo Clinic Comprehensive Cancer (MCCC). Methods: We retrospectively analyzed the medical records of pts treated with DVRd between June 2018 and June 2024 at the MCCC. Outcomes were estimated using the Kaplan-Meier method. Results: 464 pts were included; 278 pts were male, and the median (m) age of MM diagnosis was 64 years (yr). 114 pts had ISS III, 205 pts had R-ISS III, 266 pts had high risk (HR) FISH, 80 pts had extramedullary disease, 165 pts had ultra HR disease (dz) (as per 2025 IMS/IMWG consensus), and 47 pts had renal insufficiency (RI) with creatinine >2 mg/dL. Starting len dose was 25mg in 356 pts, 15 mg in 40 pts and ≤10mg in 65 pts. 399 pts received bor 1x per week and 63 2x per week, 91 pts received 1-2 cycles of a different regimen prior to DVRd due to hospitalization (n=23), RI (n=38), poor performance status (n=6), other (n=34). 315 (67.9%) pts underwent autologous transplant (ASCT). The m number of induction cycles was 5; 4 for pts who underwent ASCT and 6 for pts who did not. The best ORR to induction for pts who underwent ASCT was 98% with 247 (79%) achieving ≥VGPR, and 82 (26%) achieving minimal residual disease negativity (MRD-) to at least 10-5. The best ORR for pts who did not undergo ASCT was 87%. For those who underwent ASCT, (96% with melphalan 200mg/m2), the ORR at day 100 was 97% with 56% achieving MRD-. At 1-yr post ASCT, 30% (93/312) were MRD-. 42 pts (13%) received post ASCT cons with DVRd for a m of 2 cycles. 281 pts received post ASCT maint including 107 (38%) len, 53 (19%) bor-len, 91 (32%) dara-len, 14 (5%) dara, 16 (6%) other. 61(13%) pts had change in treatment, due to change to second line therapy (35; 55%), discontinuation (d/c) of len (11; 17%), d/c of dara (3; 5%), d/c of bor (15; 23%), d/c of dex (0; 0%). The m follow-up time for all pts was 26 months (mo) (17-39). The m PFS of pts who underwent ASCT was not reached (NR), and was 57 mo (52-NA) for pts who did not undergo ASCT. For pts who underwent ASCT, the PFS at 24mo for pts who did not have HR FISH was 93% (88-99%) compared to 80% (73-88%) for pts with HR FISH (p=0.12) and 77% (68-87%) for pts with ultra-HR dz (p=0.013).The PFS at 24mo of pts with RI who underwent ASCT was 81% (66-98%) compared to 86% (82-92%) for those without RI, p=0.57. The PFS at 24mo of pts with RI who did not undergo ASCT was 53% (28-100%) compared to 64% (55-75%) for those without RI, p=0.42. The ORR and MRD- rate for pts who received once-weekly bor was 94% and 24%, compared to 94% and 27% for pts who received 2x weekly bor (p=0.85, p=0.93). For pts who underwent ASCT, the PFS at 24mo for pts who received len maint was 91% vs. 83% for pts who receive dual agent maint (DR or VR) (p=0.25), although pts who got dual agent maint were more likely to have HR FISH than pts who received len maint (p<0.001). The PFS at 24mo for pts that received post-ASCT cons was 91% compared to 85% for those that did not (p=0.53); pts who got post-ASCT cons were more likely to have HR FISH (p=0.07). For pts that underwent ASCT, the 3 yr PFS rate is 85% and the 3 yrs OS rate is 96%. For pts that did not undergo ASCT the 3 yrs PFS rate is 60% and the 3 yr OS rate is 85%. 55 pts had functional HR (FHR) MM (relapse within 18 mo) and m PFS for FHR pts who underwent ASCT was 15 mo (11-NA), while m PFS was NR for pts without FHR MM (p<0.001). 79 pts relapsed after 1st line DVRd. The most common 2nd line therapies (tx) were dara-carfilzomib (K)-D, dara-pomalidomide(P)-D, KPD, and other. The m follow-up time from 2nd line tx was 10 mo, the best ORR to 2nd line tx was 76%, and the m PFS with 2nd line tx was 18 mo (7-NA). Conclusion: In this RW analysis, the efficacy and survival outcomes of NDMM pts treated with DVRd was comparable to that reported in the PERSEUS and GRIFFIN trials, although MRD- rates appear lower. DR maint and post-ASCT cons use was not common and was used more frequently in pts with HR FISH. Pts can be effectively salvaged following PD on front-line DVRd with available tx.

Introduction: Myeloma therapeutics have tremendously improved in recent times, leading to unprecedented outcomes. Timely initiation of effective treatment is vital to improving survival and quality of life. Patient refusal to receive treatment is infrequent but certainly leads to increased morbidity/mortality. We studied factors associated with treatment refusal. Methods: The National Cancer Database (NCDB) was queried for adult patients diagnosed with MM between 2004-2021. Those who refused treatment for initial management despite physician's recommendation were identified. Patients with multiple primary malignancies or unknown treatment status were excluded. Patients' demographics and socioeconomic factors were collected. Kaplan-Meier and multivariate Cox regression were used to evaluate the likelihood of treatment refusal in the whole cohort and in each racial/ethnic group. Results: Out of 86,350 eligible patients with MM who were recommended to initiate therapy, 2,508 (2.9%) did not receive any treatment due to refusal. Of these, 52.6% were females, 64% were non-Hispanic White (NHW), 21.3% were non-Hispanic African American (NHAA), and 5.2% were Hispanic. On multivariate analysis, patients who were treated at comprehensive and integrated facilities were more likely to refuse treatment as compared to those at academic facilities (OR=1.36; 95% CI: 1.22-1.52, p<0.001 and OR=1.22; 95% CI: 1.07-1.4, p=0.004, respectively). Patients on Medicare (OR=1.42; 95% CI: 1.16-1.73, p<0.001), and presence of higher Charlson Comorbidity Index (CCI) also had a higher likelihood of refusing treatment. Lower refusal rates were seen for male gender (OR=0.83; 95% CI: 0.76-0.91, p<0.001), NHW racial/ethnic group (as against NHAA; OR=0.34; 95% CI: 0.16-0.71, p=0.004), being insured (OR=0.69; 95% CI: 0.52-0.93, p=0.015), having private insurance (compared to Medicaid; OR=0.47; 95% CI: 0.38-0.59, p<0.001) and having a higher income level (OR=0.82; 95% CI: 0.70-0.96, p=0.013). Among NHAA patients, 2.8% refused treatment and were more likely to have Medicare (OR=1.4; 95% CI: 1.03-1.9, p=0.032). Having private insurance (compared to Medicaid; OR=0.61; 95% CI: 0.43-0.88, p=0.008) had a lower likelihood of refusing treatment. Among NHW, 2.9% refused treatment and they were more likely to be treated at community, comprehensive and integrated facilities compared to academic facilities (OR=1.39; 95% CI: 1.12-1.73, p=0.003, OR=1.54; 95% CI: 1.33-1.77, p<0.001 and OR=1.38; 95% CI: 1.16-1.64, p<0.001, respectively), be from rural areas (OR=1.43; 95% CI: 1.05-1.96, p=0.025), and have a higher CCI. On the other hand, male gender (OR=0.79; 95% CI: 0.72-0.89, p<0.001), private insurance (compared to Medicaid; OR=0.42; 95% CI: 0.30-0.59, p<0.001) and higher income level (OR=0.80; 95% CI: 0.66-0.98, p=0.029) had a lower likelihood of refusing treatment. Among Hispanic patients, 2.3% refused treatment and were more likely to have Medicare (OR=1.96; 95% CI: 1.13-3.4, p=0.016), while those with private insurance (compared to Medicaid; OR=0.32; 95% CI: 0.14-0.73, p=0.007) had a lower likelihood of refusing treatment. Conclusions: This large real-world analysis highlights the intricate sociodemographic and economic factors that affect the decision of a MM to not proceed with the recommendation for treatment. (1) NHW are less likely to refuse treatment as compared to NHAA. (2) Insurance status is an important driver of refusal and transcends race/ethnicity. Furthermore, in this study, we highlight characteristics that are specific to different racial/ethnic groups like CCI which affect only certain racial/ethnic groups. This provides an opportunity to develop targeted interventions such that the benefit of therapeutic advancements can be realized by all.

Introduction: Overall outcomes have improved significantly for MM with a 5-year relative survival rate currently of >60%. With effective treatments, patients from all clinical strata and age groups are expected to have meaningful benefit, but despite excellent therapeutic advancements, some patients continue to have early mortality. We conducted this study to investigate factors associated with early mortality. Methods: The National Cancer Database (NCDB) was queried for adult patients with NDMM between 2004 and 2021. We excluded patients with multiple primary malignancies or lost to follow-up (unknown vital status or last contact). Early mortality was defined as death within 6 months from MM diagnosis. Patient demographics and socioeconomic factors available in NCDB were collected. Kaplan-Meier and multivariate Cox regression were used to evaluate the likelihood of early mortality in this large cohort of MM patients using multi-variate analysis. Results: Out of 255,579 eligible patients with MM, 35,302 (13.8%) died within the first 6 months of diagnosis and 108,534 (42.5%) died after the first 6 months of MM diagnosis. The early mortality cohort had significantly higher mean age at MM diagnosis (73.9 vs. 68.5 years, p<0.001) but no significant differences were noted for gender distribution. There was a statistically significant difference for racial/ethnic distribution (p=0.019), but the percentages were very similar among non-Hispanic White (69% vs 68.1%), non-Hispanic African American (18% vs 18.7%) and Hispanic patients (4.7% vs 4.8%). Patients in the early mortality cohort were less likely to be treated at academic institutions (28.4% vs 37.8%, p<0.001) and have significantly different distribution by insurance type (less likely to have private insurance; 17.3% vs. 30%, more likely to have Medicare; 72.1% vs. 58.7%, p<0.001) although overall insurance access was similar between the two groups (95.3% vs 95.2%, p=0.283). Early mortality was associated with higher morbidity scores as per the Charlson-Comorbidity Index (CCI) (p<0.001) and were more likely to have not received any treatment for MM (53.2% in early mortality group vs. 28.4% in late mortality, p<0.001). Early mortality was also associated with a lower literacy rate (high school graduation rate 21.2% vs. 19.7%, p<0.001) and lower household income (<$46,277; 19.1% vs. 17.7%, p<0.001). Conclusion: This large real-world analysis shows that despite therapeutic advances in recent years, there is a significant percentage of patients with NDMM in the U.S. who suffer from early mortality. There are several sociodemographic and economic factors that were found to be associated with early mortality, with some showing clear trends (older age, treatment facility type, insurance type, income, education, CCI), while others like racial differences were significant but somewhat ambiguous. Identifying and addressing these factors at diagnosis will help provide personalized care plans and minimize early mortality.