Khera, Nandita

ABSTRACT Venetoclax (Ven) plus hypomethylating agents (HMA) is standard frontline therapy for newly diagnosed AML (ND‐AML) patients unfit for intensive chemotherapy and is also considered in younger, fit patients. However, consolidation with allogeneic stem cell transplant (ASCT) is often required to secure durable remission. The current study examines posttransplant outcomes in patients with ND‐AML treated with frontline Ven‐HMA who subsequently underwent ASCT. A total of 111 ND‐AML patients (58% male, 60% secondary/therapy‐related, median age 70 years [range, 37–80]) received a median of 3 cycles of Ven‐HMA. Mutations at the time of diagnosis included RUNX1 (18%), SRSF2 (17%), TP53 (16%), ASXL1 , IDH2 , K/NRAS , TET2 (14% each), STAG2 (11%), DNMT3A (8%). All patients were in CR/CRi at the time of transplant including 88% after Ven‐HMA. Measurable residual disease (MRD) by flow cytometry was detectable in 18/76 (24%) patients. Donors were mostly HLA‐matched unrelated (75%); 51% receiving fludarabine/melphalan conditioning and 67% posttransplant cyclophosphamide. At a median follow‐up of 15 months, 42 (38%) of patients have died and 18 (16%) experienced posttransplant relapse. Median posttransplant survival was not reached (NR), with 1‐, 2‐, 3‐year survival rates of 69%/60%/57%, respectively. On multivariate analysis, age ≥ 65 years, STAG2 mutation ( STAG2 MUT ) , and DNMT3A MUT were associated with superior posttransplant survival. Patients were stratified into low‐ (0–1 point), intermediate‐ (2 points), and high‐risk (3 points); age < 65 years, STAG2 wild type, and DNMT3A wild type, with 3‐year survival rates of 89%, 59%, and 19%, respectively ( p < 0.01). Taken together, age, STAG2 MUT and DNMT3A MUT stratified posttransplant survival in Ven‐HMA treated patients with ND‐AML.

Financial toxicity is a significant but often overlooked consequence of cancer for adolescents and young adults (AYAs, 15–39 years old), who face limited savings, unstable employment, and insurance gaps that heighten financial stress. As part of a larger initiative to determine whether our cancer center can use an existing social drivers of health (SDOH) screening process to identify patients who may benefit from targeted supportive interventions, we sought to characterize financial strain, toxicity, and SDOH needs in AYAs treated in our cancer center and compare them to both younger and older cancer patients. This is a cross-sectional observational study at Mayo Clinic of patients with an oncology-related department visit between 8 September 2023–4 June 2024 (N = 81,731) who completed routine institutional electronic screenings for financial strain and SDOH. Survey items assessed financial strain, transportation barriers, and food insecurity; institutional billing data captured financial toxicity (unresolved balances, collection referrals, write-offs). AYAs (n = 5655) were more likely than non-AYAs to report medium/high financial strain, have unpaid debt, or have an unresolved balance, referral to a collection agency, or bad debt write-off, with nearly double the odds of medium/high financial strain compared to patients over 40 (OR 2.02, 95% CI 1.84–2.23, p < 0.001). Within AYAs, ages 26–32 bore the greatest burden: 24.2% in the medium/high-risk category, 9.4% with unresolved billing issues or collections, and 11.6% reporting food insecurity. These findings identify AYAs—particularly those 26–32—as a distinct high-risk group for financial toxicity and health-related social needs, underscoring the need for targeted interventions, tailored financial navigation, and policy efforts to reduce economic barriers to care. Future research should evaluate the effectiveness of these interventions in mitigating financial toxicity, addressing health-related social needs, and improving patient outcomes in this population.

ABSTRACT The recently published BLAST clinical risk model for chronic myelomonocytic leukemia (CMML) and its molecular version (BLAST‐Mol) differentiate low, intermediate, and high‐risk groups. The objective of the current retrospective study was to examine the survival impact of allogeneic stem cell transplant (ASCT) in a consecutive series of Mayo Clinic patients ( n = 775; 68% males, median age 71 years) with CMML, overall and adjusted for baseline BLAST/BLAST‐Mol risk categories. At a median follow‐up of 77 months, 151 (20%) patients underwent ASCT. Overall survival (OS) was longer in the ASCT compared to the non‐ASCT cohorts (median 77 vs. 28 months; p < 0.01). The significant difference in OS between the ASCT and non‐ASCT cohorts was retained after adjusting for BLAST clinical risk groups: high‐risk (median 50 vs. 14 months; p < 0.01), intermediate‐risk (81 vs. 28 months; p < 0.01), and low‐risk (111 vs. 65 months; p = 0.04), respectively. The same was mostly the case when OS comparison was adjusted for BLAST‐Mol with respective p values of < 0.01, < 0.01, and 0.08, respectively. Time‐dependent cox models confirmed the favorable survival impact of ASCT in the BLAST/BLAST‐Mol high‐ and intermediate‐risk groups. The current study highlights the benefit of ASCT for BLAST/BLAST‐Mol high‐ and intermediate‐risk groups in CMML and its potential to overcome the adverse impact of some high risk cytogenetic or molecular abnormalities. These observations support the early use of ASCT in CMML, ideally before BT and regardless of genetic characteristics.

6530 Background: Venetoclax (Ven) plus hypomethylating agents (HMA) is standard frontline therapy for newly diagnosed AML (ND-AML) patients unfit for intensive chemotherapy and is also being considered in younger and fit patients (Fathi, Blood 2025). However, consolidation with allogeneic stem cell transplant (ASCT) is often required to secure durable remission. The current study examines predictors of post-transplant survival (PTS) in the particular scenario. Methods: ND-AML patients who received upfront Ven+HMA and underwent ASCT were retrospectively studied. PTS, relapse rate, and non-relapse mortality (NRM) were evaluated. Results: 111 ND-AML patients (58% male, 60% secondary/therapy-related, median age 70 [37-80 years]) received median 3 cycles of Ven-HMA. 22% had complex karyotype. Mutations at diagnosis included RUNX1 (18%), SRSF2 (17%), TP53 (16%), ASXL1 , IDH2 , K/NRAS and TET2 (14% each), STAG2 (11%), DNMT3A (8%) and at time of ASCT (N=78 evaluable); RUNX1 (8%), NPM1 (6%), TP53 and ASXL1 (5% each), and SRSF2 and TET2 (4% each). At ASCT, all patients were in CR/CRi; 88% after Ven-HMA and 12% after additional bridging therapy. MRD by flow cytometry was detected in 18 (24%) of 76 evaluable patients and complex karyotype in 8 (9%) of 94. Donors were mostly HLA-matched unrelated (75%), with 51% receiving fludarabine/melphalan conditioning and 67% post-transplant cyclophosphamide (PTCy). At a median follow-up of 30 months, 42 patients (38%) have died including 18 (40%) from relapse. Median PTS was not reached (NR) with 1-2-3-year survival of 69%/60%57%. On multivariate analysis, age ≥65 years (median NR vs 10 months p<0.01), STAG2 (NR vs 44 months; p=0.04), and DNMT3A mutations (NR vs.NR p=0.05) were associated with superior PTS. In analysis limited to variables at time of ASCT, age ≥65 years remained significant (p<0.01) while TP53 mutations, donor type, and MRD status were not (p>0.1). Patients <65 years more often received bridging therapy compared to ≥65 years (23% vs 7%; p<0.05); excluding salvage-treated patients did not change survival results. 18 patients (16%) experienced post-ASCT relapse with median RFS of 7 months. Relapse rates at 1/2/3 years were 22%, 30% and 31% and NRM 13%, 24%, 46%, respectively. Patients <65 years had a higher 1 yr relapse incidence than those ≥65 years (36% vs 18%; p=0.01), with similar NRM (p=0.58). PTCy was not associated with relapse (p=0.66) but showed a borderline association with higher NRM (1-/2-/3-year 17%/31%/58% vs 4%/7%/16% in non-PTCy recipients; p=0.06). GVHD rate was 44% (50% ≥grade 2) with no association with relapse (p=0.43) or NRM (p=0.99). Conclusions: In the current study, older age (>65 years), including >75 years, was independently associated with superior PTS in ND-AML patients receiving Ven-HMA. By contrast, PTS was not affected by genetic profile at the time of ASCT, donor type, conditioning regimen, or GVHD prophylaxis.

Telehealth may improve access to specialized oncology care for Medicaid beneficiaries with hematological malignancies who face geographic and financial barriers. During the COVID-19 public health emergency, telehealth use expanded rapidly, yet state policies governing telehealth coverage/payment parity varied. Evidence is limited on how these policy differences influenced oncology telehealth use for Medicaid patients. We conducted a cross-sectional analysis of 2020–2021 multistate Medicaid claims. Adult and pediatric oncology specialists were identified based on board certification data. Telehealth video visits were measured monthly at the extensive margin, defined as the proportion of specialists providing any telehealth, and the intensive margin, defined as average monthly telehealth visits among telehealth providing specialists. States were categorized by private insurance telehealth policy environment: coverage and payment parity, coverage parity only, or no or unspecified parity. Telehealth use increased sharply across all states in early 2020, rising from less than 1% of specialists before the pandemic to peak levels by April 2020. Specialists practicing in coverage and payment parity states demonstrated higher and more sustained telehealth use through 2021 compared with those in coverage only or no parity states. By December 2021, 15.1% of adult specialists in coverage and payment parity states provided telehealth, compared with 8.1% in coverage-only states and 7.8% in no-parity states. Pediatric specialists showed similar patterns, though overall telehealth use remained lower. Specialists in parity states also maintained higher monthly telehealth visit volumes over time. State-level coverage and payment parity policies may have been associated with greater and sustained telehealth provision by oncology specialists treating Medicaid beneficiaries with hematologic malignancies. Maintaining supportive telehealth policies may be essential for promoting equitable access to specialized cancer care and reducing disparities among underserved populations. These findings inform future telehealth policy decisions nationally statewide.

BACKGROUND: Patients with locally advanced rectal cancer face substantial costs related to multimodal therapy. However, the extent of this burden is poorly characterized. OBJECTIVE: To characterize the prevalence and predictors of patient-reported financial toxicity after treatment for locally advanced rectal cancer. DESIGN: Multicenter retrospective cohort study with a cross-sectional survey administered to assess patients’ financial concerns as well as clinicodemographic data. SETTING: Three high-volume tertiary academic centers. PATIENTS: Patients who completed treatment for pathological stage II to III rectal adenocarcinoma between 2000 and 2019 and were alive. MAIN OUTCOME MEASURES: Patient-reported financial toxicity and risk factors associated with financial toxicity. RESULTS: A total of 523 patients were identified, 190 (36.3%) responded to the survey, and 2 were excluded for incomplete surveys. Of the responders, 163 (86.7%) were identified as having financial toxicity related to their cancer diagnosis, and most (96.8%) had insurance. Patients with financial toxicity were less likely to have fully paid medical leave (39.8% vs 75%; p = 0.03) compared to patients without financial toxicity. They also reported increased difficulty paying bills ( p < 0.001) and decreased monthly household income ( p < 0.001) due to their diagnosis. Furthermore, these patients reported increased difficulty paying for transportation to medical appointments ( p = 0.002) and were less likely to be completely satisfied with their insurance coverage ( p = 0.003). Feeling well informed regarding treatment-related costs was associated with decreased odds of financial toxicity (OR 0.14; 95% CI, 0.02–0.78; p = 0.02), whereas taking unpaid leave for treatment was associated with increased odds of financial toxicity (OR 4.71; 95% CI, 1.36–16.34; p = 0.01). LIMITATIONS: Cross-sectional design and moderate response rate may introduce selection and recall bias. CONCLUSIONS: Patients undergoing treatment for locally advanced rectal cancer, including those insured, are at risk for financial toxicity due to direct and indirect costs. Effective communication between these patients and physicians regarding the economic implications of treatment is essential to reducing financial toxicity. See Video Abstract . TOXICIDAD FINANCIERA TRAS EL TRATAMIENTO DEL CÁNCER RECTAL LOCALMENTE AVANZADO ANTECEDENTES: Los pacientes con cáncer de recto localmente avanzado enfrentan costos sustanciales relacionados con la terapia multimodal. Sin embargo, la magnitud de esta carga está poco caracterizada. OBJETIVO: Caracterizar la prevalencia y los predictores de la toxicidad financiera reportada por los pacientes después del tratamiento para el cáncer de recto localmente avanzado. DISEÑO: Estudio de cohorte retrospectivo multicéntrico con una encuesta transversal para evaluar las preocupaciones financieras de los pacientes, así como datos clínico-demográficos. ESCENARIO: Tres centros académicos terciarios de alto volumen. PACIENTES: Pacientes que completaron el tratamiento para el adenocarcinoma de recto en estadio patológico II-III entre 2000 y 2019 y estaban vivos. PRINCIPALES MEDIDAS DE RESULTADOS: Toxicidad financiera reportada por los pacientes y factores de riesgo asociados con la toxicidad financiera. RESULTADOS: Se identificó a un total de 523 pacientes, 190 (36,3%) respondieron a la encuesta y 2 fueron excluidos por encuestas incompletas. De los encuestados, 163 (86,7 %) presentaron toxicidad financiera relacionada con su diagnóstico de cáncer, y la mayoría (96,8 %) contaba con seguro médico. Los pacientes con toxicidad financiera tuvieron menos probabilidades de tener licencia médica con goce de sueldo completo (39,8 % frente a 75 %; p = 0,03) en comparación con los pacientes sin toxicidad financiera. También informaron mayor dificultad para pagar facturas ( p < 0,001) y una disminución de los ingresos familiares mensuales ( p < 0,001) debido a su diagnóstico. Además, estos pacientes informaron mayor dificultad para pagar el transporte a las citas médicas ( p = 0,002) y menor probabilidad de estar completamente satisfechos con su cobertura médica ( p = 0,003). Sentirse bien informado sobre los costos relacionados con el tratamiento se asoció con una menor probabilidad de toxicidad financiera (OR: 0,14; IC del 95 %: 0,02-0,78; p = 0,02), mientras que tomar una licencia sin sueldo para el tratamiento se asoció con una mayor probabilidad de toxicidad financiera (OR: 4,71; IC del 95 %: 1,36-16,34; p = 0,01). LIMITACIONES: El diseño transversal y la tasa de respuesta moderada pueden introducir sesgos de selección y de recuerdo. CONCLUSIONES: Los pacientes en tratamiento para el cáncer de recto localmente avanzado, incluidos los asegurados, corren el riesgo de sufrir toxicidad financiera debido a los costos directos e indirectos. Una comunicación eficaz entre estos pacientes y los médicos sobre las implicaciones económicas del tratamiento es esencial para reducir la toxicidad financiera. ( AI-generated translation )

Introduction People most likely to be affected by Alzheimer’s disease and related dementias (ADRD) are underrepresented in clinical research. Identifying and addressing factors which may influence their research participation is important to advance science and promote diversity. We examined the influence of social determinants of health (SDOH) on research participation among people living with ADRD. Methods We included those age 55 years and older living with ADRD, followed in our community practice in Rochester, Minnesota, who completed a questionnaire assessing SDOH and had at least one clinic visit between June 1, 2019 and June 1, 2020. Demographic and SDOH factors were examined by research participation. Results Among 3273 people included, research participation was low overall (265/3273; 8.1%). People participating in research were more likely to be socially integrated and of higher educational attainment (p < 0.05). Conclusion Promoting social interaction is a potential area for focus to increase research participation in at risk populations.

Abstract The comparative value of liposomal cytarabine/daunorubicin (CPX-351) versus venetoclax plus a hypomethylating agent (Ven-HMA) in the frontline treatment of older adults with primary ( de novo ) or secondary acute myeloid leukemia (AML) remains uncertain. In the current study, we retrospectively examined outcomes of 600 patients with newly diagnosed AML treated with CPX-351 (N = 112) or Ven-HMA (N = 488). AML subtypes included de novo (46%), post-myelodysplastic syndrome (MDS) (19%), post-myeloproliferative neoplasm (MPN) (12%), post-MDS/MPN (6%), therapy-related (17%) and AML with myelodysplasia-related genetic abnormalities (AML-MR; 46%). Patients receiving CPX-351 were younger (median 65 vs. 73 years; p < 0.01), predominantly female (50% vs. 38%; p = 0.02), more likely to have secondary AML (68% vs. 51%; p < 0.01), and less likely to harbor NPM1 MUT (5% vs. 12%; p = 0.02). Rates of complete response with or without count recovery (CR/CRi) were comparable between CPX-351 and Ven-HMA (55% vs. 60%; p = 0.30), including in AML-MR (60% vs. 63%; p = 0.70). Ven-HMA use was associated with fewer infectious complications (62% vs. 83%; p < 0.01) and yielded higher CR/CRi rates in males (60% vs. 45%; p = 0.04), de novo AML (68% vs. 50%; p = 0.03), and in the presence of STAG2 MUT (86% vs. 44%; p = 0.02), or CEBPA MUT (88% vs. 50%; p = 0.03). Overall survival censored for transplant, was similar (median 10 vs. 13 months; p = 0.90), with Ven-HMA being superior in post-MDS AML (median 12 vs. 7 months; p = 0.02) and CPX-351 in the presence of SF3B1 MUT (not reached vs. 14 months; p < 0.01). Our findings suggest that Ven-HMA is as effective and less toxic than CPX-351 in newly diagnosed AML, including AML-MR, despite selection of younger, fitter patients for CPX-351.

Abstract Introduction Management of acute leukemia (AL) during pregnancy remains challenging. In the first trimester, chemotherapy is toxic to the fetus, while delaying treatment may endanger maternal health, often prompting recommendations for pregnancy termination. In later trimesters, although the risk of congenital malformations decreases, complications such as preterm labor remain prevalent. Delivery prior to chemotherapy may be considered in advanced gestation. This study aimed to describe maternal and fetal outcomes of patients diagnosed with AL during pregnancy. Methods Following institutional review board approval, we retrospectively identified pregnant patients diagnosed with AL between 1995 and 2025 across Mayo Clinic sites (Minnesota, Arizona, Florida). We recorded leukemia subtype, treatment course, maternal and fetal outcomes. Results We identified 18 patients diagnosed with AL during pregnancy, including 11 with acute myeloid leukemia (AML) and 7 with acute lymphoblastic leukemia (ALL). Ten were diagnosed in the first trimester, 3 in the second, and 5 in the third. In the AML group (n=11; median age 30 years, range 18-42), one patient had acute promyelocytic leukemia (APL). ELN 2022 risk stratification was favorable in 5 (45%), intermediate in 4 (36%), and adverse in 2 (18%). In the ALL group (n=7; median age 23 years, range 19-34), 5 had B-ALL (one Philadelphia chromosome-positive) and 2 had T-ALL. All ALL cases were diagnosed in the first trimester. Among first-trimester AMLs, 2 of 3 had core-binding factor (CBF) AML. All eight patients diagnosed in the second and third trimesters had AML (1 APL, 2 CBF AML, 1 KMT2A-rearranged, 1 with DEK::NUP214 fusion, 1 complex karyotype including t(8;21), 2 with normal karyotype). Overall, 15 (83%) patients achieved complete remission (CR) or CR with incomplete count recovery (CRi) after initial induction. One patient had refractory disease and achieved partial remission after salvage, another had refractory disease and achieved CR after multiple lines of therapy, and a third achieved CR after FLAG-idarubicin and revumenib. Five patients received chemotherapy during pregnancy (3 in the first trimester, 1 in the second, 1 in the third); two of these resulted in live births. Among the 10 patients diagnosed in the first trimester, all underwent therapeutic or spontaneous abortion. Of the 3 second-trimester diagnoses, 2 underwent spontaneous or therapeutic abortion at 15 weeks. The third received 7+3 induction at 24 weeks for KMT2A-rearranged AML, followed by preterm delivery at 26 weeks and re-induction with FLAG-idarubicin plus revumenib, achieving CR. Among the 5 third trimester diagnoses, 4 delivered preterm infants (median gestational age 33 weeks) prior to chemotherapy. One patient received 7+3 at 29 weeks and delivered a viable preterm infant at 36 weeks. At a median follow-up of 6.5 years, 5 of 11 patients with AML (45%) and 3 of 7 patients with ALL (43%) died, mostly due to disease progression. Median overall survival was not reached in either group. Causes of death were as follows: 1 of AML, 1 of ALL, 3 of acute stem cell transplant (SCT) complications, 1 of chronic SCT complications, 1 of Hodgkin lymphoma, and 1 of pneumonia. Among patients diagnosed in the second and third trimesters (n=8, all with AML), 6 (75%) resulted in live births: 5 of 5 (100%) third-trimester diagnoses and 1 of 3 (33%) second-trimester diagnoses. All received intensive induction: 7+3 (n=5), 7+3 + ATRA (n=1), 7+3 + gilteritinib (n=1), and 7+3 + nilotinib (n=1). Of the second-trimester group, only one received induction prior to delivery; she later achieved CR with FLAG-ida and revumenib. Among the third-trimester group, one patient received chemotherapy prior to delivery and achieved CR followed by SCT. All but one of the 8 AML patients achieved CR after initial therapy. Conclusions Successful pregnancy outcomes were achieved in 75% of patients diagnosed with AML during the late second or third trimester. Notably, 5 (28%) of patients received chemotherapy during pregnancy. Larger, multi-institutional cohorts are warranted to further characterize the incidence and outcomes of AL in pregnancy.