At what COST?: A prospective longitudinal cohort assessment of financial toxicity, quality of life, and associated risk factors in patients with plasma cell disorders.

Financial toxicity is prevalent and harmful to patients with plasma cell disorders.

Association of Thrombocytopenia With Disease Burden, High-Risk Cytogenetics, and Survival in Newly Diagnosed Multiple Myeloma Patients Treated With Novel Therapies.

BACKGROUND: The effect of thrombocytopenia has not been studied in the era of novel treatments in multiple myeloma (MM). OBJECTIVE: To evaluate the clinical characteristics and outcomes in MM patients presenting with thrombocytopenia. MATERIALS: Newly diagnosed MM patients between 2008 and 2018 who received at least 2 novel agents at induction. Thrombocytopenia was defined as a platelet count of less than < 150,000/mm3. RESULTS: A total of 648 patients were identified. Thrombocytopenia was found in 120 patients (18.5%). Baseline disease characteristics associated with higher rates of thrombocytopenia at baseline included IgA myeloma, P < .01, ISS 3 versus 1 or 2, P < .01, R-ISS 3 versus 1 or 2, P < .01, renal failure (CrCl < 30 mL/min), P < .01, hypercalcemia (Ca > 11.5 mg/dL), P < .01, elevated LDH, P < .03, anemia (Hb < 10 g/dL), P < .01, higher serum monoclonal protein, P < .02, and > 60% plasma cells in the bone marrow, P < .01. Thrombocytopenia was more prevalent across patients with t(4;14) and t(14;16), but was not associated with an overall high-risk fluorescence in situ hybridization (FISH) classification. Median OS was significantly lower among patients with thrombocytopenia (64.4 vs. 145.0 months, P < .01). In multivariable Cox regression, thrombocytopenia was associated with mortality (HR = 2.45, 95% CI, 1.7-3.6) independently of age, sex, high-risk FISH, ISS stage, response at induction, percentage of plasma cells in the BM, and anemia. CONCLUSION: We found that thrombocytopenia was seen among one-fifth of MM patients and was more common in patients with (t[4; 14] and t[14; 16]). Thrombocytopenia had an independent association with worse survival.

Clinical features associated with poor response and early relapse following BCMA-directed therapies in multiple myeloma.

Three classes of BCMA-directed therapy (BDT) exist: antibody drug-conjugates (ADCs), CAR-T, and T-cell engagers (TCEs), each with distinct strengths and weaknesses. To aid clinicians in selecting between BDTs, we reviewed myeloma patients treated at Mayo Clinic with commercial or investigational BDT between 2018-2023. We identified 339 individuals (1-exposure = 297, 2-exposures = 38, 3-exposures = 4) who received 385 BDTs (ADC = 59, TCE = 134, CAR-T = 192), with median follow-up of 21-months. ADC recipients were older, with more lines of therapy (LOT), and penta-refractory disease. Compared to ADCs, CAR-T (aHR = 0.29, 95%CI = 0.20-0.43) and TCEs (aHR = 0.62, 95%CI = 0.43-0.91) had better progression-free survival (PFS) on analysis adjusted for age, the presence of extramedullary (EMD), penta-refractory disease, multi-hit high-risk cytogenetics, prior BDT, and the number of LOT in the preceding 1-year. Likewise, compared to ADCs, CAR-T (aHR = 0.28, 95%CI = 0.18-0.44) and TCEs (aHR = 0.60, 95%CI = 0.39-0.93) had superior overall survival. Prior BDT exposure negatively impacted all classes but was most striking in CAR-T, ORR 86% vs. 50% and median PFS 13-months vs. 3-months. Of relapses, 54% were extramedullary in nature, and a quarter of these cases had no history of EMD. CAR-T demonstrates superior efficacy and where feasible, should be the initial BDT. However, for patients with prior BDT or rapidly progressive disease, an alternative approach may be preferable.

Academic Promotions in Medicine: An Appraisal of Fairness.

OBJECTIVE: To investigate whether the process of conferring academic rank or components of the promotion packet contribute to the lack of parity in academic advancement for women and individuals underrepresented in medicine (URMs). PATIENTS AND METHODS: We retrospectively reviewed prospective promotion applications to the position of associate professor or professor at Mayo Clinic from January 2, 2015, through July 1, 2019. Individuals with doctorate degrees who applied for either rank were included in the study. Data collected included demographic characteristics, curriculum vitae at time of application, committee score sheets, and deferral and approval decisions. Deferral rates for women compared with men and for URMs compared with non-URMs was the primary outcome. RESULTS: Of 462 people who applied for associate professor, 10% (n=46) were deferred. Those promoted had worked longer at Mayo Clinic (median, 6 years vs 2 years; P=.01), had more mentees (median, 6 vs 4; P=.02), authored more publications (median [interquartile range (IQR)], 39 [32-52] vs 30 [24-35]; P<.001), and were more likely to be on a National Institutes of Health or institutional grant (P<.05). Of the 320 people who applied for professor, 8.8% (n=28) were deferred. Those promoted had authored more publications (median [IQR], 77 [60-99] vs 56 [44-66]; P<.001) and were less likely to hold an elected office to a professional society (22.6% vs 39.3%; P=.05). There was no significant association between deferral status and sex (P>.4) or race/ethnicity (P>.9) for either rank. CONCLUSION: The process for academic advancement for professorships does not contribute to the gap in promotion rates for women and URMs.

A Mixed-Method Approach to Explore Successful Recruitment and Treatment of Minority Patients on Therapeutic Cancer Clinical Trials at a Tertiary Referral Center Using Photo-Elicitation Interviews.

Introduction: Under-represented minority patients (URM) enroll in cancer clinical trials (CCT) at low rates. To gain insight into barriers and facilitators to CCT enrollment, we conducted a mixed method study of URM patients who were successfully treated on a therapeutic CCT from 2018-2021 at all institutional sites. Methods: A retrospective chart review of 270 minority patients was conducted to identify patient demographics and characteristics. All living URM patients were requested to participate in a survey and qualitative interview using a photo elicitation technique. Results: Most patients who participated in a CCT were patients with solid tumors, metastatic disease, and did not live in a rural area. Survey data showed that the two most significant drivers of CCT enrollment were potential of benefit to self and to others (altruism). Direct recommendation from a healthcare provider to participate in CCT was critical. URM patients enrolled on a CCT experience a significant burden of symptoms and financial distress. Key themes identified from the interviews that motivated patients to participate included chance for cure, staying positive, altruism and advancement of science, and having diverse representation in research. Patient-level facilitators to participation included social support, cost coverage, and limited treatment options. Sytematic facilitators identified included minimizing logistical barriers, decentralizing cancer clinical trials, increasing awareness via patient narratives, diversifying research staff, minimizing cost, and being clear on puropose and benefit of the trial. Conclusion: Success stories of minority recruitment can provide useful information to enhance minority accrual. Photo elicitation interviews provide rich narratives of patient experience.

Outcomes of patients with multiple myeloma refractory to standard dose vs low dose lenalidomide.

Refractoriness to lenalidomide is an important factor determining the choice of therapy at first relapse in multiple myeloma (MM). It remains debatable if resistance to lenalidomide varies among MM refractory to standard doses vs low dose maintenance doses. In this study, we assessed the outcomes with subsequent therapies in patients with MM refractory to standard dose vs low dose lenalidomide. We retrospectively reviewed all patients with MM at our institution who received first line therapy with lenalidomide containing regimens, and assessed progression free survival (PFS) and overall survival for these patients for second line therapy, and with lenalidomide retreatment. For second line therapy, we found no difference in the PFS between standard dose refractory and low dose refractory groups (median PFS 14 months vs 14 months, p = 0.95), while the PFS for both these groups was inferior to the not refractory group (median PFS 30 months, p < 0.001 for both pairs). Similar trends were seen among these groups on lenalidomide retreatment, and on multivariable analysis. These data suggest that refractoriness to lenalidomide is not dose dependent, and definition of lenalidomide refractoriness should not depend on the dose of lenalidomide to which the disease was considered refractory.

Mode of progression in smoldering multiple myeloma: a study of 406 patients.

The approach to patients with high-risk smoldering multiple myeloma (SMM) varies among clinicians; while some advocate early intervention, others reserve treatment at progression to multiple myeloma (MM). We aimed to describe the myeloma-defining events (MDEs) and clinical presentations leading to MM diagnosis among SMM patients seen at our institution. We included 406 patients diagnosed with SMM between 2013-2022, seen at Mayo Clinic, Rochester, MN. The 2018 Mayo 20/2/20 criteria were used for risk stratification. Median follow-up was 3.9 years. Among high-risk patients who did not receive treatment in the SMM phase (n = 71), 51 progressed by last follow-up; the MDEs included: bone lesions (37%), anemia (35%), hypercalcemia (8%), and renal failure (6%); 24% met MM criteria based on marrow plasmacytosis (≥60%) and/or free light chain ratio (>100); 45% had clinically significant MDEs (hypercalcemia, renal insufficiency, and/or bone lesions). MM diagnosis was made based on surveillance labs/imaging(45%), testing obtained due to provider suspicion for progression (14%), bone pain (20%), and hospitalization/ED presentations due to MM complications/symptoms (4%). The presentation was undocumented in 14%. A high proportion (45%) of patients with high-risk SMM on active surveillance develop end-organ damage at progression. About a quarter of patients who progress to MM are not diagnosed based on routine interval surveillance testing.

Daratumumab-lenalidomide and daratumumab-pomalidomide in relapsed lenalidomide-exposed or refractory multiple myeloma.

Daratumumab is an anti-CD38 mAb, used frequently in combination with lenalidomide and pomalidomide. No studies compared daratumumab plus lenalidomide and dexamethasone (DRd) to daratumumab plus pomalidomide and dexamethasone (DPd) in lenalidomide-exposed multiple myeloma. We identified 504 consecutive multiple myeloma patients who received daratumumab at Mayo Clinic between January 2015 and April 2019. We excluded patients who received daratumumab in the first line, received more than four lines of therapy prior to daratumumab use, did not receive lenalidomide prior to daratumumab, or had an unknown status of lenalidomide exposure, and patients who received daratumumab combinations other than DRd or DPd. We examined the impact of using DRd compared to DPd on progression-free survival (PFS) and overall survival (OS) in patients with relapsed/refractory multiple myeloma. Out of 504 patients, 162 received DRd or DPd and were included; 67 were lenalidomide-exposed and 95 were lenalidomide-refractory. DRd was used in 76 (47%) and DPd in 86 (53%) patients. In lenalidomide-exposed multiple myeloma, there was no difference in median PFS; 34.2 months [95% confidence interval (CI), 22.8-44.6] for DRd compared to 25.2 months (95% CI, 4.9-35.3) for DPd, P  = 0.2. In lenalidomide-refractory multiple myeloma, there was no difference in median PFS; 18.6 months (95% CI, 13-32) for DRd compared to 9 months (95% CI, 5.2-14.6) for DPd, P  = 0.09. No difference in median OS was observed in DRd compared to DPd. Our study shows combining daratumumab with lenalidomide in patients with prior lenalidomide use is a viable and effective treatment option.

Predictors and Impact of Timing of Disease Progression Following Primary Therapy in Multiple Myeloma.

In multiple myeloma (MM) significant variation in progression-free survival (PFS) and overall survival (OS) is observed. We examined the outcomes of 1557 MM patients stratified into short (<2 years), medium (between 2 and 5 years) and long (>5 years) PFS. Short PFS occurred in 758 patients (48.7%), medium in 561 patients (36.2%), and long in 238 patients (15.3%). Median post-progression PFS was 9.2 months (95% CI: 8.1-11.0) in the short PFS and 33.1 months (95% CI: 29.0-42.1; P < .001) in the long PFS group. Median post-progression OS was 26.6 months (95% CI: 23.9-29.8) in the short PFS and 87.8 months (95% CI: 71.3- NR; P < .001) in the long PFS. Worse survival in the short PFS was irrespective of high risk (HR) fluorescence in situ hybridization (FISH) features, defined as deletion 17p and/or translocation t(4;14), t(14;16), t(14;20). In a multivariable analysis short PFS was associated with HR FISH, extramedullary plasmacytoma, plasma cell labeling index ≥2% at diagnosis, nonimmunoglobulin G isotype, treatment without autologous stem cell transplantation and achieving less than very good partial remission. In conclusion, the duration of the PFS significantly influences survival, regardless of HR cytogenetic features. Therefore, it should be considered an important parameter for risk stratification in patients experiencing a relapse.

Muscle and fat composition in patients with newly diagnosed multiple myeloma.

Measures of muscle and adipose tissue mass have been associated with outcomes in several malignancies, but studies in multiple myeloma (MM) are inconsistent. The aim of this study was to evaluate the association between muscle and fat areas and radiodensity, and overall survival (OS) in patients with newly diagnosed MM. We included 341 patients diagnosed with MM from 2010-2019 who had an 18F-fluorodeoxyglucose positron emission tomography/computed tomography at diagnosis. A cross-sectional image at the third lumbar vertebrae was segmented into muscle and fat components. Median follow up was 5.7 years. There was no association between sarcopenia and baseline disease characteristics or OS. Low muscle radiodensity was associated with higher disease stage, anemia, and renal failure. OS was 5.6 vs. 9.0 years in patients with muscle radiodensity in the lower vs. middle/upper tertiles, respectively (P = 0.02). High subcutaneous adipose tissue (SAT) radiodensity was associated with higher stage, anemia, thrombocytopenia, hypercalcemia, renal failure, and high LDH. OS was 5.4 years vs. not reached in patients with SAT radiodensity in the upper vs. middle/lower tertiles, respectively (P = 0.001). In conclusion, sarcopenia was not associated with OS in MM patients. High SAT radiodensity and low muscle radiodensity were associated with advanced disease stage and adverse laboratory characteristics.

Mode of Progression in Smoldering Multiple Myeloma: A study of 406 patients.

The approach to patients with high-risk smoldering multiple myeloma (SMM) varies among clinicians; while some advocate early intervention, others reserve treatment at progression to multiple myeloma (MM). We aimed to describe the myeloma-defining events (MDEs) and clinical presentations leading to MM diagnosis among SMM patients seen at our institution. We included 406 patients diagnosed with SMM between 2013-2022, seen at Mayo Clinic, Rochester, MN. The 2018 Mayo 20/2/20 criteria were used for risk stratification. Median follow-up was 3.9 years. Among high-risk patients who did not receive treatment in the SMM phase (n=71), 51 progressed by last follow-up; the MDEs included: bone lesions(37%), anemia(35%), hypercalcemia(8%), and renal failure(6%); 24% met MM criteria based on marrow plasmacytosis (≥60%) and/or free light chain ratio (>100); 45% had clinically significant MDEs (hypercalcemia, renal insufficiency, and/or bone lesions). MM diagnosis was made based on surveillance labs/imaging(45%), testing obtained due to provider suspicion for progression(14%), bone pain(20%), and hospitalization/ED presentations due to MM complications/symptoms(4%). The presentation was undocumented in 14%. A high proportion (45%) of patients with high-risk SMM on active surveillance develop end-organ damage at progression. About a quarter of patients who progress to MM are not diagnosed based on routine interval surveillance testing.

Relationships Among Health Insurance Literacy, Financial Toxicity, and Sociodemographic Factors in Patients With Cancer.

PURPOSE: The objective of the study was to describe the prevalence of health insurance literacy (HIL) and investigate how patient-reported outcome measures assessing HIL are related to financial toxicity in patients with cancer. METHODS: We assessed HIL and financial toxicity in 404 patients enrolled between December 2019 and January 2021 at two medical centers in the United States. We conducted exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) to explore and test the relationships among the factors and items. We fit structural equation models (SEMs) to find the relationships among the factors and sociodemographic/clinical characteristics. RESULTS: The EFA revealed items loaded on four factors: knowledge about health insurance, confidence related to HIL (HIL confidence), information-seeking behavior related to health insurance, and financial toxicity. The four-factor CFA model had good fit statistics (comparative fit index, 0.960; Tucker-Lewis index, 0.958; root mean square error of approximation, 0.046; and standardized root mean square residual, 0.086). In SEM, income, education level, and race positively predicted knowledge about health insurance. Knowledge about health insurance and number of total lines of cancer treatment was positively associated with HIL confidence. Higher income, older age, and HIL confidence were associated with less financial toxicity. Higher levels of financial toxicity, HIL confidence, and knowledge were associated with greater information-seeking behavior. CONCLUSION: Our findings showed how different aspects of HIL are related to financial toxicity even after adjustment for sociodemographic and clinical characteristics. Future studies should investigate the longitudinal relationships among these factors to help develop interventions to mitigate financial toxicity.

Outcomes of patients with primary refractory multiple myeloma in the era of triplet and quadruplet induction therapy.

Patients with multiple myeloma (MM) who do not respond to initial therapy have worse outcomes than primary responders, and effective treatments are lacking in this population. However, the outcomes of primary refractory disease in the modern treatment era have not yet been studied. We reviewed patients with MM treated with triplet/quadruplet therapy at our institution to assess the incidence of primary refractory disease and the impact of salvage therapies in this population. We identified 1127 patients, of whom 1086 were evaluated for hematologic responses after 4 to 6 cycles. Of these, 93.3% (1013) had evidence of response, whereas 6.7% (73) had primary refractory disease. With a median overall survival (OS) of 51.3 months, patients with primary refractory disease had an increased risk of shorter survival in univariable and multivariable analyses (hazard ratio [HR], 3.5 [95% confidence interval (CI), 2.5-4.9]; HR, 4.3 [95% CI, 2.6-6.9], respectively). In the subgroup analysis of patients with primary refractory disease, those who received second-line autologous stem cell transplantation (ASCT) had increased second progression-free survival (20.9 vs 8.1 months; P < .01) and second OS (74.7 vs 31.3 months; P = .02) compared with patients who did not. We conclude that early progression remains a significant factor for shorter OS in the current era, and salvage ASCT could be the most beneficial option for this population.

Long-term outcomes of allogeneic stem cell transplant in multiple myeloma.

Allogeneic stem cell transplant (allo SCT) for multiple myeloma (MM) is potentially curative in some, while toxic in many others. We retrospectively analyzed 85 patients diagnosed with MM who underwent allo SCT as frontline or salvage therapy between 2000 and 2022 at Mayo Clinic Rochester and examined patient outcomes and prognostic markers. Overall survival (OS), progression free survival (PFS), treatment related mortality (TRM), and relapse rates (RR) were estimated using the Kaplan Meier method and competing risk models. Median follow-up was 11.5 years. Median OS and PFS were 1.7 and 0.71 years, respectively. Five-year OS and PFS were 22.2% and 15.1%, respectively. One-year TRM was 23.5%. Twelve patients demonstrated durable overall survival, living 10+ years beyond their allo SCT. This subgroup was more likely to have no or one prior auto SCT (p = 0.03) and to have been transplanted between 2000 and 2010 (p = 0.03). Outcomes were poor in this cohort with long follow-up, with few patients surviving 5 years or more, and most relapsing or dying within 2 years. We would expect better outcomes and tolerability with an expanded array of novel therapeutics and would prefer them to allo SCT.