Shah, Surbhi

Abstract INTRODUCTION: Warm autoimmune hemolytic anemia (wAIHA) is a rare, autoimmune-mediated hematologic disorder associated with significant morbidity and mortality and may occur as a primary condition or secondary to an underlying disorder. It is the most common subtype of autoimmune hemolytic anemia (AIHA), accounting for 75-80% of AIHA cases. Older adults with wAIHA are particularly vulnerable, as they often have multiple comorbidities and are already at elevated risk of death. This study aimed to assess mortality associated with wAIHA. METHODS: Adults with wAIHA (wAIHA cohort) and without AIHA (non-AIHA cohort) were identified from the 100% Medicare Fee-for-Service database (10/01/2019–12/31/2023). Evidence of wAIHA was defined as one of the following: 1) a primary wAIHA diagnosis (International Classification of Diseases, Tenth Revision, Clinical Modification [ICD-10-CM]: D59.11) in the inpatient setting (first instance of wAIHA diagnosis defined the index date), 2) ≥2 wAIHA diagnosis in any setting ≥30 days apart (second instance of wAIHA diagnosis defined the index date), or 3) a wAIHA diagnosis preceded ≥30 days by any AIHA diagnosis (ICD-10-CM: D59.10, D59.19, D59.8, D59.9; first instance of wAIHA diagnosis defined the index date). Patients in the wAIHA cohort were excluded if they had a diagnosis for cold or mixed-type AIHA (ICD-10-CM: D59.12, D59.13) during the baseline period (12 months before index). The non-AIHA cohort had no diagnoses for any AIHA during the study period; a random index date during continuous Medicare eligibility was selected and patients were matched 1:10 with the wAIHA cohort based on age on index date. Using overlap weighting, age-matched cohorts were further weighted on sex, race, region, index year, and baseline comorbidities associated with mortality, excluding conditions defining secondary wAIHA. Mortality during the follow-up period was evaluated between the weighted cohorts using the Kaplan-Meier method and Cox proportional hazard models. Patients whose death was not observed were censored at the earlier of the end of continuous Medicare eligibility or data availability. RESULTS: 3,112 and 31,120 patients were included in the wAIHA and non-AIHA cohorts, respectively. After weighting, among the wAIHA vs non-AIHA cohorts, mean [standard deviation; SD] age was 74.4 [11.6] vs 74.6 [11.2] years, the proportion of female were 56.1% vs 56.1%, mean [SD] Quan-CCI without secondary wAIHA-defining conditions was 1.9 [2.0] vs 1.9 [2.1], and mean [SD] follow-up time was 17.2 [11.7] vs 14.9 [11.4] months, respectively. In addition, 53.7% of the wAIHA cohort had secondary wAIHA. The most common secondary wAIHA-defining conditions were autoimmune and inflammatory diseases (wAIHA cohort: 27.8%; non-AIHA cohort: 11.0%), hematologic and lymphoproliferative disorders (wAIHA cohort: 23.8%; non-AIHA cohort: 1.3%), and solid tumors (wAIHA cohort: 16.8%; non-AIHA cohort: 12.6%). The most common comorbidities for both cohorts were hypertension (wAIHA cohort: 77.4%; non-AIHA cohort: 78.3%) and dyslipidemia (wAIHA cohort: 72.2%; non-AIHA cohort: 74.7%). Survival rates in the wAIHA and non-AIHA cohorts were 80.3% vs 84.0% at 12 months, 70.7% vs 77.6% at 24 months, and 63.7% vs 73.1% at 36 months, respectively (all p<0.001). Patients with wAIHA were at 20%, 27%, and 30% higher risk of death at 12, 24, and 36 months, respectively, compared to patients without AIHA (hazard ratios: 1.20, 1.27, and 1.30; all p<0.001). CONCLUSIONS: This large retrospective study is the first to assess real-world incremental mortality associated with wAIHA among Medicare beneficiaries. Patients with wAIHA were at significantly greater risk of death following the initial diagnosis. These results may point to potential gaps in early diagnosis and effective disease management, which could contribute to increased mortality. Future research should focus on specific subgroups within the wAIHA cohort to identify differences in mortality as well as characteristics that may be associated with death.

Abstract Introduction: Warm autoimmune hemolytic anemia (wAIHA) is a rare, life-threatening, relapsing, autoantibody-driven disease associated with a significant physical, emotional, and quality of life burden on patients and caregivers. In rare diseases like wAIHA, patients more often rely on publicly available online disease information to improve their health literacy, however available data and educational resources on the internet are often limited. Rapidly evolving technology has led to a rise in patients and care partners utilizing online digital health resources to gather information and seek support. Developing patient-facing educational materials in collaboration with the end user may help increase utilization and engagement, which would facilitate improving patient health. This qualitative patient research aimed to gather feedback from individuals living with wAIHA on creative concepts for a disease state education website and to gain insight on proposed content areas for the educational resource. Methods: A wAIHA patient council was convened to better understand the perspective of individuals living with wAIHA. US-based adults with a self-reported diagnosis of wAIHA who were members of the patient council participated in a 2-hour virtual focus group to discuss a wAIHA disease state education website concept and provide insight into potential gaps in patient education. Participants were permitted to provide feedback in an online questionnaire as an alternative to joining the session. The session focused on reviewing the website design concept and four proposed content areas. Focus group discussions were audio-recorded and transcribed. Transcripts were qualitatively analyzed to identify key themes and insights. Results: Four individuals living with wAIHA participated in the virtual focus group and one gave feedback via the online survey. Most participants were female (80%) and White (60%). Participants expressed an unmet need for a reliable and easy to understand educational website that could be utilized by patients, care partners, and their loved ones throughout the wAIHA journey. The most important information for the wAIHA educational website, as identified by participants, included disease state information (ranging from basic disease explanations/definitions to comprehensive data on the disease), resources for patient support groups, and patient testimonials. Proposed content areas included suspected wAIHA, understanding wAIHA, living with wAIHA, and resources and support; these were all deemed valuable by participants. They recommended enhancements like creating a dedicated section for family and care partners, offering guidance on parenting with wAIHA, and providing further explanations of disease-related terms and resources. Insights gathered on the initial website design concept provided actionable changes to content such as alternative imagery to emphasize the wAIHA community and refinement of text to reinforce the website as a guiding tool for patients and care partners. Participant feedback was incorporated into the final concept resulting in a patient-centered digital resource. Conclusions: Including perspectives of individuals living with wAIHA in the development of patient-facing educational resources is key to creating impactful tools for the intended user. Insights collected from this exploratory research directly contributed to the improvement of the concept for a wAIHA disease state education website, making it more engaging and impactful. This research demonstrates the value of focus groups in gaining insight into patient preferences for educational resources and guiding their development to be customized for the end user.

Abstract Introduction A 2017 survey by the American Society of Hematology found a widespread perceived shortage of classical hematologists in the US, which was compounded by a low trainee interest in the field (<5%) (Masselink LE, Blood Adv 2019). Recently, we reported that among hematologist/oncologists at the 64 National Cancer Institute (NCI)-designated cancer centers with clinical programs, only ~5% identify as classical hematologists, despite 15% of them including classic hematology (CH) patients in their practice (Go LT, Blood Adv, in press). However, there remains limited data on CH consult volumes at NCI-designated cancer centers (West CV, JCO Oncol Pract 2023). This study aimed to evaluate the volume and nature of CH outpatient consults at the Mayo Clinic Comprehensive Cancer Center (MCCC). Methods We reviewed electronic medical records to identify all completed outpatient consults in CH, malignant hematology (MH), and solid tumor oncology at MCCC in Rochester, Minnesota from January 1 to December 31, 2024. Consults were defined as either external or internal referrals for new patients seen in CH outpatient clinic. CH consults were further categorized by referral reasons and the type of physician (CH, MH, or fellow) performing the consultations. CH physicians were defined as those whose clinical practice primarily focuses on non-malignant hematologic conditions; one advanced practice provider (APP) was included in this group. Inpatient consults, electronic consults, and return visits were excluded. Results In 2024, a total of 17,153 outpatient consults were completed. Of these, 13.4% were CH, 30.5% were MH and 56.1% were solid tumor oncology. Among CH consults, the most common referral reasons were abnormal blood counts (68.3%), bleeding disorders (10.6%), thrombosis (11.8%), and other hematologic diagnoses (9.3%). Within abnormal blood counts, the leading indications were anemia (50.7%), thrombocytopenia (15.3%), leukopenia (11.0%), leukocytosis (9.1%), and pancytopenia (7.0%). Among bleeding disorders, the top reasons included suspected bleeding diathesis (49.4%), von Willebrand disease (24.5%), Hemophilia A (4.1%), Factor VII deficiency (3.7%), and platelet qualitative defect (3.4%). Thrombosis-related consults were most often for pulmonary embolism or deep vein thrombosis (43.2%), antiphospholipid syndrome (17.7%), thrombophilia (16.2%), portal vein thrombosis (4.1%), and splenic infarct (2.6%). The top ten referrals for a specific hematologic diagnosis were iron deficiency anemia (29.2%), pulmonary embolism or DVT (13.5%), immune thrombocytopenic purpura (10.3%), von Willebrand disease (6.9%), hemoglobinopathy (5.5%), antiphospholipid syndrome (5.5%), thrombophilia (5.1%), anemia of chronic kidney disease (2.4%), aplastic anemia (1.5%), and hereditary spherocytosis (1.4%). Of the 114 physicians at MCCC during the study period, 55 (48.2%) were medical oncologists, 54 (47.4%) primarily practiced MH, and only 5 (4.4%) were dedicated CH physicians. Despite comprising only 4.4% of the hematology/oncology workforce, CH physicians or fellows completed the majority (86.1%) of CH consults; MH physicians completed 13.8%. Conclusion CH consults represent a substantial portion of outpatient hematology referrals at MCCC, primarily for diagnostic evaluation of cytopenias or thrombotic/bleeding symptoms. However, a striking mismatch exists between CH physician representation (4.4%) and CH consult volume (13.4%). This imbalance has implications for quality, timeliness, and continuity of care for patients with non-malignant hematologic conditions. Our findings underscore the urgent need to expand recruitment and career development pathways in CH to address a huge clinical demand.

Abstract Background: In 2022, Medicare alone spent $42.1 billion on prescription drugs, with antineoplastic and classical hematology drugs accounting for 44% and 8% of the total, respectively (2024 MedPAC Data Book). While antineoplastic drugs have been extensively studied, classical hematology drugs have received comparatively little attention. We analyzed US Food and Drug Administration (FDA) approvals of classical hematology drugs over the past 30 years and examined their per-patient costs and annual total US sales. Methods: We identified all classical hematology drugs (those prescribed by hematologist/oncologists for non-malignant indications) approved by the FDA from January 1, 1995 to December 31, 2024, including novel pharmaceuticals (synthesized from chemical compounds), biologics (derived from living organisms), and biosimilars (highly similar, but not identical, to biologics previously approved). Cost estimates for 2024 were based on wholesale acquisition costs (WAC), using annual WAC for continuous-duration treatments and typical course WAC for fixed-duration treatments. WAC and US gross sales data for 2024 were obtained from IPD Analytics (Aventura, FL). Results: A total of 98 classical hematology drugs were approved over the past 30 years—11% in 1995–2004, 26% in 2005–2014, and 63% in 2015–2024. These included pharmaceuticals (36%), biologics (54%), and biosimilars (10%). Six gene therapies received approval: 3 for hemophilia and 1 each for sickle disease, beta thalassemia, and sickle cell disease/beta thalassemia (dual indication). Common categories of indications included bleeding (31%), anemia (30%), neutropenia (9%), and thrombocytopenia (9%). Leading diagnoses were hemophilia (25%), chemotherapy-induced neutropenia (9%), thromboembolism (8%), paroxysmal nocturnal hemoglobinuria (PNH; 7%), anemia of chronic kidney disease (6%), iron deficiency anemia (6%), and immune thrombocytopenia (5%). The median cost for gene therapies was $2.9 million per treatment (range: $2.2 million–$3.5 million). Among non-gene therapies, median costs were $3,000 per course for fixed-duration treatments (range: $64–$378,000) and $467,000 annually for continuous-duration treatments (range: $2,400–$1.8 million). The most expensive fixed-duration treatments targeted hemophagocytic lymphohistiocytosis ($378,000/8-week course), while the most expensive continuous-duration treatments were for hemophilia (median: $630,000/year; range: $270,000–$853,000). Estimated 2024 US gross sales across all drugs exceeded $70 billion. Top-selling indications included thromboembolism ($43.5 billion), hemophilia ($6.9 billion), immune thrombocytopenia ($4.9 billion), PNH ($4.7 billion), chemotherapy-induced neutropenia ($2.8 billion), anemia of chronic kidney disease ($2.0 billion), and iron deficiency anemia ($1.8 billion). Total sales for all gene therapies combined were $143 million. Six drugs have been discontinued (year approved/year discontinued/reason): betrixaban (2017/2020/business), daprodustat (2023/2024/business), fidanacogene elaparvovec (2024/2025/business), oprelvekin (1997/2011/business), peginesatide (2012/2013/safety), and voxelotor (2019/2024/safety). There are limitations to our study. Some drugs have non-classical hematology indications (anticoagulants in atrial fibrillation; luspatercept in myelodysplastic neoplasm) and/or may also be prescribed by non-classical hematologists (erythropoiesis stimulating agents by nephrologists and medical oncologists). We were unable to disaggregate the sales data in these situations. Therefore, the annual sales for certain indications may be overestimated. Conclusions: Classical hematology drugs contribute substantially to US prescription drug spending, with over $70 billion in annual sales and medications for thromboembolism accounting for over half of the costs. Approvals have accelerated over the past three decades, doubling each decade. Biologics and biosimilars now represent two-thirds of approvals. Continuous-duration treatments, particularly for rare hereditary diseases like hemophilia, carry significant financial burden, with annual costs per patient often exceeding $0.5 million. In these conditions, if gene therapies demonstrate durable efficacy, they may prove to be cost-effective alternatives. As more gene therapies are developed, evaluating their long-term value relative to chronic high-cost treatments will be essential for shaping future reimbursement and access strategies.