Wolf, Emily

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.

9029 Background: Addressing guideline concordant FP and TPP with cancer is challenging, especially for OT. SIM, a well-known education tool, has not been traditionally used to teach these topics. As part of the hematology/oncology fellowship curriculum, we designed a SIM applying LSP to bridge this educational gap. Methods: Applying LSP of contrasting cases, elaboration, feedback, generation and just-in-time telling, chief OTs and faculty designed a SIM with 3 clinical scenarios (CS) and 3 standardized pts (SP): FP for a female pt hospitalized for acute lymphoblastic leukemia tx, FP for a male pt in clinic for germ cell tumor tx, and breast cancer tx for a pregnant pt in 2 nd trimester. OT received written educational materials (WEM) and attended a lecture 1 week and 1 day pre SIM, respectively. OT were split into 2 groups; 1 started in the FP CS and 1 in the TPP CS, and then they switched. To reduce cognitive overload, each OT participated in 1 of 2 FP CS: half in the female FP CS and half in the male. Faculty and chiefs led debriefing sessions after all CS. The FP debrief ended with a special “learner as a teacher” part, where OT who attended the female CS taught those from the male CS about their topic and vice versa. The SIM concluded with "take-home" points. Pre (after having WEM) and post SIM anonymous surveys and verbal feedback assessed OT comfort, perceptions, and knowledge. Results: A 3 hour SIM with 14 OT and 5 faculty was completed successfully. SIM ended with all OT verbally sharing a learning point and positive feedback. All OT filled pre and post SIM surveys. Pre SIM, 17% reported having prior FP education, and 42% had prior TPP education. However, only 8% and 25% felt adequately prepared for FP and TPP discussions, respectively. Post SIM survey showed major improvement in comfort and knowledge about FP and TPP (see table 1). 75% of OT favored a combination of SIM and learning by teaching over other SIM formats. 83% supported having a TPP lecture before SIM. 100% reported satisfaction with FP and TPP SIM’s quality and wanted similar activities in the future. 92% were satisfied with the learner as a teacher tool. 100% felt education about FP and TPP with cancer should be part of fellowship training. Moral/cultural concerns were discussed as possible challenges in FP education. Conclusions: The application of LSP through SIM significantly increased OTs’ comfort discussing FP and TPP with cancer, and objectively enhanced their knowledge on these topics compared to after reading WEM. The SIM was largely perceived as a successful activity to educate about challenging topics and should become part of fellowship curriculum. Pre SIM % Post SIM % Comfortable addressing FP 17 92 Comfortable addressing TPP 8 100 Correct answers about female FP 63 83 Correct answers about male FP 67 94 Correct answers about TPP with cancer 68 98

e16610 Background: Adrenocortical carcinoma (ACC) is a rare malignancy with an incidence of 1-2 per million per year. The optimal treatment remains unclear as does the benefit of chemotherapy (chemo) in patients (pts) with resectable ACC. Methods: The SEER database (2000–2021) was used to identify ACC pts > 18 years. Variables of interest included age, race, household income, rural-urban classification, stage, chemo, radiation therapy (RT), and surgery. Statistical analyses were conducted using ANOVA, Kruskal-Wallis, and Kaplan-Meier methods to compare survival outcomes according to variables of interest. Results: Of the 2,598 pts identified, 1,564 (60%) were female. The majority of pts (85%) were white, followed by black (9%). Most pts (87%) resided in metropolitan areas. Pts with localized, regional, or distant metastatic disease comprised 25%, 17% and 36% of the group, respectively. 40% of pts underwent radical or total surgical removal of the primary site disease while 9%, 2%, and 1% underwent partial surgical removal, excision, or debulking surgery, respectively, and 30% did not undergo surgery. 34% of pts received chemo and 8% received RT. The median overall survival (mOS) for the entire cohort was 15 months (m) (95% CI: 14–17 m). No significant differences in OS were observed among pts of different races or household incomes. Distant metastatic disease was significantly associated with worse mortality when compared with regional or localized diseases (mOS: 5 m vs. 20 m vs 60.6 m, respectively, p < 0.001). Surgical intervention of any kind was associated with longer survival when compared to those who did not undergo surgery (18 m vs. 3 m, HR 0.33, p < 0.0001). Among the 971 pts with distant metastatic disease, pts who received chemo had a superior mOS compared to those who did not receive chemo or with unknown chemo status (8 m vs. 2 m, p < 0.0001). This OS advantage remained significant even after excluding pts who underwent surgery (5 m vs. 2 m, p < 0.0001). While chemo was also associated with longer mOS (29 m vs. 27 m, p < 0.0001) in localized disease, this survival advantage was not present in pts with localized disease managed with surgery (27 m vs. 27 m, p = 0.061). Although chemo was associated with numerically longer mOS in pts with regional disease, the difference was not significant. Conclusions: ACC with distant metastatic disease carries a poor prognosis yet demonstrates superior survival in pts who receive chemo. Surgery is associated with better survival outcomes, but there is no additive benefit from chemo in those with localized disease managed with surgical resection.

Lung cancer remains the leading cause of cancer-related mortality worldwide. Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer, with nearly half of all patients diagnosed at an advanced stage. Immune checkpoint inhibitors (ICIs) harness the host immune system to combat malignant cells. ICIs, which target programmed death-ligand 1 (PD-L1), programmed cell death 1 (PD-1), and cytotoxic T-cell lymphocyte-4 (CTLA-4), have transformed the treatment landscape for advanced NSCLC. While a subset of patients experiences a long-term durable response, most patients will develop disease progression. New drugs targeting novel pathways are being tested in clinical trials to improve the efficacy of immunotherapy and overcome resistance patterns. This review aims to summarize the currently available ICIs for advanced NSCLC and describe emerging immunotherapies with recently published data from phase I/II clinical trials.

Introduction: CAR-T (chimeric antigen receptor T-cell) therapy is known to be associated with immune-mediated toxicities including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). [18F]-Flurodeoxyglucose-positron emission tomography (FDG-PET) is frequently utilized for cancer staging before and after CAR-T therapy. Case series have demonstrated cerebral glucose hypometabolism (CGHM) on FDG-PET imaging in patients who developed CRS and ICANS. In this study, we aim to further characterize CART-CGHM. Methods: Patients who received CAR-T therapy at our institution from October 2019 to December 2023 were included. Clinical data was collected from retrospective review of the electronic medical record including patient age, sex, diagnosis, cancer stage, development of CRS or ICANS, and survival outcome. Standard of care whole body FDG-PET scans obtained before and approximately 30 days post CAR-T therapy were utilized. FDG-PET images of the brain were sub-selected and processed with dedicated imaging software (GE AW server 3.2 with Cortex ID, MIM Neuro, version 7.2.7). To identify CART-CGHM, visual and statistical comparison was made between the pre-CAR-T FDG-PET and the post-CAR-T FDG-PET using the age and gender matched normal cohort in the database as controls. Z-score changes &gt; 1.5 were considered significant. Baseline variables were reported as frequency (%) and compared between patients with and without CGHM using Chi-squared test. Kaplan-Meier method was used to estimate the overall survival rate (OS) at different time points and log rank test was used to compare survival rates between the groups with and without CGHM. Multivariable Cox regression model was performed to evaluate the association between CGHM and OS with adjustment for ICANS. All tests were two-sided with p&lt;0.05 considered statistically significant. Results: In total, 84 patients (41 women, 49%) were included. The median age at time of CAR-T therapy was 66 (33-85) years old. The most common diagnosis was multiple myeloma (n=39, 46%) followed by diffuse large B-cell lymphoma (n=33, 39%), follicular lymphoma (n=7, 8%), mantle cell lymphoma (n=3, 4%), and B-cell acute lymphoblastic leukemia (n=2, 2%). CART-CGHM was identified in 27 patients (32%). The pattern of CGHM was either global (n=15, 56%) or focal (n=12, 44%) with the prefrontal cortex predominantly affected. Of these 27 patients with CART-CGHM, 17 patients (63%) experienced ICANS and 23 patients (85%) experienced CRS. The diagnosis of lymphoma and development of ICANS were significantly associated with CGHM (p- 0.038 and &lt;0.001 respectively). On univariate analysis, CGHM and ICANS were associated with negative impact on OS. The post-CAR-T 12-month OS for patients with CGHM was 76% versus 84% without CGHM (p-0.016), and 12-month OS for patients with ICANS was 64% versus 91% without ICANS (p-0.001). The post-CAR-T median OS for patients with CGHM, patients with ICANS, and patients with both CGHM and ICANS were 17.1 months, 13.5 months, and 12.6 months, respectively. On multivariate analysis, after adjusting for ICANS, CGHM alone did not have an impact on OS [HR 1.76 (0.71, 4.37); p-0.2250] but ICANS continued to have a negative impact on OS [HR 3.03 (1.21, 7.57); p-0.0178]. Conclusions: Our study represents the largest study to date on CART-CGHM. CART-CGHM was seen in 32% of CAR-T patients and had a strong association with ICANS and lymphoma patients. ICANS was found in 63% of CART-CGHM patients. ICANS alone or CGHM with ICANS were associated with a negative impact on OS. Although the underlying biological mechanism of CART-CGHM is not clear, it likely represents a significant immune-mediated reduction in cerebral glucose uptake. We suggest that CGHM represents a novel metabolic complication of CAR-T therapy and significantly contributes to CAR-T therapy associated neuro-cognitive toxicity. Although CART-CGHM can resolve completely, our study also showed patients with persistent CGHM on post-CART follow up FDG-PET scans. As such, CART-CGHM can potentially result in chronic neuro-cognitive complications. The current therapeutic interventions for CRS and ICANS do not appear to be adequately effective for CART-CGHM. Further research, involving multiple institutions, is urgently needed for better understanding of CART-CGHM and to develop specific therapeutic interventions.

Niacin, an important component of a balanced diet, is central to lipid metabolism. Occasionally used to treat hyperlipidemia, niacin is widely available without a prescription, making its use often unknown to treating physicians. Severe hepatotoxicity has been reported with niacin use. In the following report, we describe a case of hospitalization for acute decompensated cirrhosis with cholestatic morphology in a patient taking self-initiated large quantities of extended-release niacin. Despite medical management and support, the patient unfortunately expired on day 16 of hospitalization. Given ease of access and unclear long-term benefit in hyperlipidemia, the current case serves to raise awareness of niacin’s potential hepatotoxicity through highlighting a severe outcome. Although mode of liver injury remains unknown, the use of extended-release niacin formulations and prolonged high-dose supplementation is associated with enhanced hepatotoxicity. Careful review and counseling of commonly available supplements remains an important task of both hospital and primary care physicians.

Factor VII (FVII) is an important, vitamin K-dependent clotting factor. Acquired FVII deficiency is a rare entity that is associated with serious bleeding complications. We report a case of acquired FVII deficiency in a patient with recurrent chronic myeloid leukemia in blast crisis who developed bilateral retinal hemorrhages. The coagulopathy was corrected with the initiation of chemotherapy and subsequent reduction in peripheral blast count.