Aperna, Fnu

Cancer-associated venous thromboembolism (CA-VTE) is a leading, severe, and potentially life-threatening complication in patients with malignancy. Low–molecular-weight heparin has historically been the standard of care; however, direct oral anticoagulants, particularly direct factor Xa inhibitors, have emerged as effective alternatives. These agents offer the convenience of oral administration, predictable pharmacokinetics, elimination of routine laboratory monitoring, and improved adherence. Despite the expanding role of direct oral anticoagulants in CA-VTE management, concerns regarding bleeding risk—particularly in patients with gastrointestinal and genitourinary malignancies—remain central to clinical decision-making. In this narrative review, we evaluate the efficacy, safety, and clinical applicability of apixaban for the treatment and prophylaxis of CA-VTE. Current evidence from randomized controlled trials, including CARAVAGGIO and AMPLIFY, demonstrates that apixaban has noninferior efficacy compared with low–molecular-weight heparin and conventional anticoagulation strategies, with comparable or lower rates of recurrent venous thromboembolism. In addition, apixaban appears to have a favorable safety profile, with no statistically significant increase in major bleeding in selected cancer populations, including those without active gastrointestinal lesions. Apixaban’s pharmacokinetic properties, including limited renal clearance and stable drug exposure, further enhance its clinical utility in oncologic populations. However, evidence supporting apixaban use across all cancer subtypes remains limited and heterogeneous, highlighting the need for additional comparative and real-world studies.

Abstract Background: The International Consensus Classification (ICC) for systemic mastocytosis (SM) recognizes mast cell leukemia (MCL) and SM with associated myeloid neoplasm (SM-AMN) as distinct categories of advanced SM (SM-Adv; Arber et al. Blood 2022;140:1200). Contemporary risk models in SM, including the Mayo Alliance Prognostic System (MAPS), do not account for the prognostic heterogeneity among ICC-defined SM-Adv subcategories. Methods: Mayo Clinic databases were utilized to access patient information. Diagnoses of SM and its morphological subcategories were confirmed through clinical evaluations and review of BM pathology. Diagnostic criteria were retrospectively fitted to be consistent with those of the ICC (Arber et al. Blood 2022;140:1200); diagnosis of MCL required the presence of immature cytomorphology of mast cells and only myeloid neoplasms were listed under the category of SM-AMN.Next-generation sequencing and cytogenetic studies was performed in a subset of the study patients according to previously described methodologies. Statistical analyses were conducted on clinical and laboratory data collected at the time of initial diagnosis while survival analysis was censored at the time of allogeneic stem cell transplant (ASCT). Results: A total of 910 Mayo Clinic patients with SM (median age 56 years, range 12-89; males 50%) were accessed in order to conduct a series of multivariable analyses (MVA) in search of independent risk factors for transplant-censored overall survival (OS). All patients were evaluable for assignment to specific ICC categories of SM: indolent (ISM; N=553), aggressive (ASM; N=114), SM-AMN (N=235), and MCL (N=8); the AMN components in SM-AMN included acute myeloid leukemia (N=18), chronic myelomonocytic leukemia (N=70), myelodysplastic syndromes (N=32), MDS/myeloproliferative overlap (N=81), myelofibrosis (N=7), polycythemia vera or essential thrombocythemia (PV/ET; N=19), and others (N=8). In addition, subsets of patients were evaluable for hemoglobin level (N= 865), white blood cell count (WBC; N=858), platelet count (N= 859), serum alkaline phosphatase (ALP; N=761), serum tryptase level (N=706), karyotype (N=574), and mutations (N=240). Median follow-up for living patients was 70 months (range, 0-520); during this time 346 (38%) deaths, 16 leukemic transformations, and 20 ASCTs were documented. ROC analysis-determined optimal cutoff levels for predicting OS included age at ≥60 years, platelet count <150 x 109/L, tryptase level ≥100 ng/mL, WBC ≥10 x 109/L, hemoglobin below sex-adjusted lower limit of normal (anemia), and ALP >210 U/L in women or >170 U/L in men (increased). All except WBC ≥10 x 109/L retained significance during MVA that included ICC-specified SM categories: MCL (HR 74.8, 26.0-215.3; p<0.01); SM-AMN (HR 3.9, 2.5-6.0; p<0.01); ASM (HR 2.2, 1.4-3.5; p<0.01); age ≥60 years (HR 3.3, 2.2-4.7; p<0.01); platelets <150 x 109/L (HR 2.8, 2.0-3.9; p<0.01); tryptase ≥100 ng/mL (HR 2.1, 1.5-2.9; p<0.01); anemia (HR 1.7, 1.1-2.4; p<0.01); and increased ALP (HR1.5, 1.1-2.0; p=0.01). A subsequent HR-weighted risk model effectively delineated 5 risk levels ranging in median survivals from 11 months to 372 months (Figure 1). Figure 2 outlines complementary subtype-specific risk models; to that end, risk factors for ISM included age ≥60 years (HR 4.5, 2.5-7.9), tryptase ≥100 ng/mL (HR 3.5, 2.1-6.0); platelets <150 x 109/L (HR 3.4, 1.5-7.9), and anemia (HR 2.4, 1.2-4.8); for ASM age ≥60 years (HR 2.3, 1.3-4.3), platelets <150 x 109/L (HR 2.4, 1.4-4.0), and anemia (HR 2.0, 1.2-3.4); and for SM-AMN age ≥60 years (HR 2.9, 1.6-5.2), platelets <150 x 109/L (HR 2.5, 1.6-3.9), and tryptase ≥100 ng/mL (HR 2.5, 1.6-3.9) [Figure 2]. In SM-AMN, additional prognostic relevance from subcategorization into PV/ET vs. all other types of AMN was appreciated (Figure 3; HR 4.0, 1.6-3.9) and incorporated into the risk model for SM-AMN (Figure 2). Abnormal karyotype (AK) and high risk mutations(HRM; ASXL1, SRSF2, RUNX1, NRAS)clustered withSM-AMN with AK and ASXL1MUT displaying independent prognostic relevance that was most apparent in SM-AMN. Conclusions : MAPS-R relies on the prognostic eminence of ICC-defined morphologic subcategories and allows for additional SM subtype-specific risk stratification. SM associated with ET or PV is a prognostically unique subcategory of SM-AMN and should be recognized as such in future classification schemes. SM-AMN must be thoroughly ruled out in the presence of AK or HRM.

Abstract Background Nodal peripheral T-cell lymphomas (nPTCLs) are a challenging group of non-Hodgkin lymphomas that frequently recur after or are refractory to first line (1L) treatment. Chemotherapy options in the relapsed or refractory (R/R) setting are limited. The incorporation of non-cytotoxic agents including antibody drug conjugates, immune checkpoint inhibitors, epigenetic modifiers, and phosphatidylinositol 3-kinase inhibitors offers new therapeutic potential and possibly better outcomes. We report on outcomes for patients (pts) with R/R nPTCL enrolled in the multi-center LEO-MER prospective cohort study (NCT02736357) who received second line (2L) therapy. Methods Six hundred and three adult pts with newly diagnosed nPTCL were prospectively enrolled in the University of Iowa/Mayo Clinic MER observational cohort (2002-2015) or the expanded LEO cohort (2015-2020). Secondary overall survival (sOS) was calculated from date of 2L treatment initiation to date of death or last follow-up. Secondary event-free survival (sEFS) was calculated from date of 2Ltreatment initiation to disease progression, initiation of 3rd line therapy, or death from any cause. sEFS and sOS were evaluated using Cox model and Kaplan-Meier estimator. Log-rank test was used to test the significance of difference between groups. Pts with concomitant B-cell lymphomas were excluded from this analysis. Results Thus far, 169 pts with nPTCL initiating 2L therapy were evaluated. Of these, 75 (44.4%) had PTCL-NOS, 63 (37.3%) had angioimmunoblastic T-cell lymphoma (AITL, inclusive of nodal T-follicular helper cell lymphoma), 20 (11.8%) had ALK-negative anaplastic large cell lymphoma (ALCL), and 11 (6.5%) had ALK-positive ALCL. At 2L treatment initiation, the median age was 64 with 86.1% of pts having advanced stage disease. Of the 108 pts with available international prognostic index (IPI) scoring, 46.3% had an IPI of ≥3. Thirty-four (20.1%) pts had received a consolidative autologous stem cell transplant (ASCT) in the 1L. A total of 86 pts (50.1%) had primary refractory disease (partial response, stable or progressive disease as best response to 1L therapy), 45 (26.6%) experienced early relapsing disease within 6 months of 1L therapy, and 38 (22.5%) had relapsed disease >6 months from 1L therapy. After a median follow-up of 7.1 years (yrs), median sOS was 1.52 yrs, and sEFS was 3.2 months (mos). There was no difference in sOS or sEFS regardless of timing of relapse. In keeping with other studies, ALK-positive ALCL pts had the best 5-year OS (70.1%) compared to other subgroups (ALK-negative ALCL 45.0%, AITL 30.4%; PTCL-NOS 21.3%). Lymphoma was the leading cause of death following 2L therapy, with a 2-year cumulative incidence of 49.2%. Eighty pts (47.3%) received only cytotoxic chemotherapy as second line (2L) therapy; ICE (41 (51.3%)) and gemcitabine-containing regimens were most common (14 (17.5%)). Seventy-five pts (44.4%) were treated with non-cytotoxic agents given as monotherapy or in combination with chemotherapy. The most common non-cytotoxic therapies were brentuximab vedotin (33 (44.0%)), romidepsin (17 (22.7%)) and immune checkpoint inhibitors (9 (12.0%)). Fourteen pts (8.3%) underwent palliative interventions involving radiation, steroids, or cyclosporine alone. Intent to proceed to transplant in the 2L was known in 158 pts (101 (63.9%) not intended, 57 (36.1% intended)). Following 2L treatment, 18 (10.7%) pts proceeded to consolidative ASCT and 10 (5.9%) to allogeneic transplant. Only 21 (12.9%) were treated on a clinical trial. Pts who received a non-cytotoxic agent had superior outcomes compared to pts receiving only chemotherapy; the median sOS was 30.4 mos (95% confidence interval [CI] 15.3, 53.52 mos) vs 11.7 mos ((95% CI 7.95,19.58); p=0.04; HR 0.67) and the median sEFS was 4.83 mos (95% CI 3.38, 10.09) vs 2.33 mos ((95% CI 1.71,3.02); p=0.02; HR=0.65). Conclusions We report here one of the largest prospective cohorts in R/R nPTCL. The LEO-MER cohort, despite its association with academic centers, shows poor outcomes regardless of refractory or relapsed disease, frequent inability to proceed to intended consolidative transplant, and low clinical trial participation in 2L, which corroborates findings from other registries (Jain 2025, Stuver 2019). Outcomes improved for pts treated with non-cytotoxic agents. Updated data including additional pts and subgroup analyses will be reported at the meeting.

Hyperkalemia is a common and potentially life-threatening electrolyte abnormality in patients with heart failure, particularly among those with diabetes or chronic kidney disease. It often results from the use of renin–angiotensin–aldosterone system inhibitors, which, while improving survival, increase serum potassium levels. Elevated potassium produces cardiotoxic effects, often recognized by characteristic electrocardiographic changes. Acute management focuses on stabilizing cardiac membranes with intravenous calcium and shifting potassium intracellularly through insulin-dextrose, β₂-agonists, or sodium bicarbonate, with caution to avoid fluid overload. Potassium elimination may be achieved using diuretics or hemodialysis when refractory. For chronic management, newer potassium-binding agents such as patiromer and sodium zirconium cyclosilicate offer improved safety and efficacy compared with traditional resins, enabling the continuation and up-titration of renin–angiotensin–aldosterone system inhibitors. These therapies support optimal neurohormonal blockade, improve adherence, and reduce morbidity and mortality in heart failure.

ABSTRACTThe current study includes 910 patients with systemic mastocytosis (SM) seen at the Mayo Clinic from 1968 to 2024. The primary objective was to examine the prognostic contribution of the International Consensus Classification (ICC), in the context of the Mayo Alliance Prognostic System (MAPS) for SM. World Health Organization classification (WHO‐HAEM5) subcategories included (i) indolent/smoldering SM (ISM/SSM; N = 518), (ii) SM associated with another hematological neoplasm (SM‐AHN; N = 273), with the latter including both myeloid and lymphoid neoplasms, (iii) aggressive SM (ASM; N = 106), and (iv) WHO‐defined mast cell leukemia (MCL; N = 13), which included mast cells with both “mature” and “immature” morphology. The ICC‐defined subcategories were mostly similar with the exception that SM‐AHN was replaced by SM associated with another myeloid neoplasm (SM‐AMN; N = 235) and WHO‐defined MCL was replaced by ICC‐defined MCL (N = 8), which included only those with immature MC morphology. Overall survival (OS) was similar between WHO‐defined MCL (median 1.8 years) vs. SM‐AHN (median 2.3 years; p = 0.3) but significantly different between ICC‐defined MCL (median 0.08 years) vs. SM‐AMN (median 2.0 years; p < 0.01). Significant difference in OS was also apparent between ICC‐defined SM‐AMN and SM associated with lymphoid neoplasm (SM‐ALN; median 8.1 years; HR 3.4; p < 0.01). Multivariable analysis confirmed the inter‐independent prognostic contributions of both ICC‐defined morphologic subcategories and MAPS risk variables, including age > 60 years, anemia, alkaline phosphatase > ULN, and platelet count < 150 × 109/L (p < 0.03 in all instances); the same was not true for WHO‐HAEM5‐defined SM subcategories. The addition of mutational information into the multivariable model resulted in ousting anemia and inclusion of ASXL1 (p < 0.01), SRSF2 (p = 0.01), and NRAS (p = 0.01) mutations as additional risk factors. Classification of SM by ICC is prognostically more accurate, compared to WHO‐HAEM5, and strengthens the prognostic contribution of morphology to current clinical and molecular risk models.

6579 Background: Treatment strategies in chronic myelomonocytic leukemia (CMML) are not standardized and include hydroxyurea (HU) and hypomethylating agents (HMA). In a phase 3 study comparing HU and decitabine, in proliferative CMML, response rates were higher for decitabine (56% vs 31%; p<0.01) but overall survival was similar (p=0.67) between the two groups (Itzykson, R. JCO, 2023. 41:1888). In the current retrospective study, we examined the survival impact of different treatment strategies among 457 Mayo Clinic patients with CMML. Methods: The current study was conducted under institutional review board approved minimum risk protocols allowing retrospective patient data collection and analysis. Diagnostic criteria were according to the International Consensus Classification (Arber et al. Blood 2022. 140:1200). All statistical analyses were conducted using JMP 17 software. For survival analysis, patients were censored at time of allogeneic stem cell transplant (ASCT). Results: A total of 457 patients were considered (median age 72 years; 68% males). 209 patients received CMML-directed therapy: HU (N=102), HMA (N=78; azacitidine 32 and decitabine 46). Responses were adjudicated separately for leukocytosis and anemia; normalization of leukocyte count was achieved in 21% vs. 16 % (p<0.01) for HU vs. HMA and overall response in anemia in 1% vs. 9% (p=0.02), respectively. Overall survival did not appear to be impacted by different treatment strategies at any stage of CMML; (i) treated vs. untreated (p=0.3), (ii) HU vs. HMA for first-line therapy (p=0.3), and (iii) HU/HMAs vs. other drugs as first-line therapy (p=0.1). Blast transformation-free survival (BTFS) was also similar between HU vs. HMA as well as HU/HMA vs. other drugs. In univariate analysis, BTFS was inferior in patients receiving CMML-directed therapy (p<0.01); the particular association (HR 2; 95% CI 1.2-3.3) retained its significance in multivariable analysis that also included other risk factors for BTFS: bone marrow blast ≥10% (HR 4.3), circulating blast ≥2% (HR 2.7), WBC ≥13 x 10 9 /L (HR 1.8), and ASXL1 mutation (HR 1.7). Conclusions: In the current retrospective study that included a large number of patients with CMML, chemotherapy with HU or HMA did not appear to affect overall survival but might have increased the risk of blast transformation. The study also suggests superiority of HU for the treatment of leukocytosis and HMA for anemia. Predictors of blast transformation-free survival (BTFS) in 457 patients diagnosed with chronic myelomonocytic leukemia (CMML). BTFS Univariable analysis p-value (HR) Multivariable analysis p-value (HR) CMML-directed therapy <0.01 (2.9; 1.8-4.7) <0.01 (2; 1.2-3.3) Bone marrow blasts ≥10% <0.01 (12.4) 0.01 (4.3) Circulating blasts ≥2% <0.01 (5.2) <0.01 (2.7) WBC ≥13 x 10 9 /L <0.01 (2.9) 0.02 (1.8) ASXL1 mut <0.01 (2.1) 0.02 (1.7)

e18596 Background: The International Consensus (ICC), but not the 5 th edition of the WHO classification (WHO5), distinguishes mature from immature mast cell leukemia (MCL) and systemic mastocytosis (SM) associated with myeloid neoplasm (SM-AMN) from SM associated with myeloid or lymphoid neoplasm (SM-AHN). The objectives of the current study were i) to assess prognostic input from disease classification by ICC vs. WHO5, and ii) to compare the predictive performance of the Mayo Alliance Prognostic scoring (MAPS) with other prognostic models and its prognostic interaction with the ICC-based morphologic classification. Methods: Study patients met diagnostic criteria per ICC/WHO5. MAPS risk variables included i) age >60 years, ii) hemoglobin below sex-adjusted lower limit of normal, iii) platelets <150 × 10⁹/L, iv) alkaline phosphatase above upper limit of normal, and v) advanced, including MCL, SM-AMN, and aggressive (ASM) vs. indolent/smoldering (ISM/SSM) SM. ICC-defined MCL includes only MCL-immature whereas WHO-defined MCL includes both MCL-immature and MCL-mature. WHO-defined SM-AHN includes SM-AMN and SM associated with lymphoid neoplasm (SM-ALN). Results: 910 Mayo Clinic patients with SM were diagnosed between 1968 and 2024 (median age 56 years). ICC categories were ISM/SSM (N=552), ASM (N=115), SM-AMN (N=235), and MCL (N=8). At median follow-up of 4 years, 345 (38%) deaths and 35 (3.8%) leukemic transformations were documented. Overall survival (OS) predictive performance at 5 years was superior with ICC (AUC 0.85), compared to WHO5 (AUC 0.83); median survival was 24.3 years in ISM/SSM, 5.8 years for ASM, 2.0 years for SM-AMN, 2.3 years for SM-AHN, 1.8 years for MCL-mature and 0.08 years for MCL-immature; the difference in OS was significant between MCL-immature and SM-AMN (p<0.01) but not between MCL-mature and SM-AHN (p=0.3). Similarly, OS was similar between MCL-mature and ASM (p=0.8) and between SM-ALN and ASM (p=0.08) but different between MCL-immature and ASM (p<0.01), SM-AMN and ASM (p<0.01), and MCL-mature and MCL-immature (p<0.01). Predictive performance at 5 years was superior with MAPS (AUC 0.91) and MAPS-molecular (AUC 0.91), compared to the mutation-adjusted risk score (MARS; AUC 0.82). Median OS estimates were not reached, 24.2, 11.7, 5.7, 2.6, and 0.7 years, in the presence of 0, 1, 2, 3, 4, or 5 of the forementioned MAPS risk factors. Among informative cases, ASXL1 mutation was the only genetic risk factor with MAPS-independent prognostic relevance. Prognostic inter-independence between ICC and MAPS was confirmed by multivariable analysis. Conclusions: The current study confirms the superior performance of MAPS, in regard to survival prediction, with little additional contribution from mutations. SM sub-classification by the ICC is prognostically independent of MAPS and more valuable than classification by WHO5.

We sought to develop a survival model in chronic myelomonocytic leukemia (CMML) that is primarily based on clinical variables and examine additional impact from mutations and karyotype. 457 molecularly-annotated patients were considered. Multivariable analysis identified circulating Blasts ≥2% (1 point), Leukocytes ≥13 x 109/L (1 point), and severe (2 points) or moderate (1 point) Anemia as preferred risk variables in developing a clinical risk Stratification Tool for overall survival (OS), acronymized to "BLAST": low-risk (0 points; median 63 months); intermediate-risk (1 point; median 28 months; HR 2.2, 95% CI 1.6-3.0), and high-risk (2-4 points; median 13 months; 5.4, 4.1-7.3); the corresponding 3/5 year OS rates were 68%/53%, 43%/18%, and 12%/1%. BLAST model performance (AUC 0.77/0.85 at 3/5-years) was shown to be comparable to that of the molecular CMML-specific prognostic scoring system (CMML-mol; AUC 0.73/0.75) and the international prognostic scoring system-molecular (IPSS-M; AUC 0.73/0.74). Multivariable analysis of mutations and karyotype identified PHF6MUT and TET2MUT as being "favorable" and DNMT3AMUT, U2AF1MUT, BCORMUT, SETBP1MUT, ASXL1MUT, NRASMUT, PTPN11MUT, RUNX1MUT, TP53MUT, and adverse karyotype, "unfavorable". Molecular information was subsequently encoded in a combined clinical-molecular risk model (BLAST-mol; AUC 0.80/0.86 at 3/5-years) that included the aforementioned BLAST clinical risk variables and a 3-tiered molecular risk score. BLAST and BLAST-mol were subsequently validated by two separate external cohorts. Independent risk factors for blast transformation included DNMT3AMUT, ASXL1MUT, PHF6WT, leukocytes ≥13 x 109/L, and ≥2% circulating or ≥10% bone marrow blasts. The current study proposes an easy to implement, globally applicable, and molecularly adaptive risk model for CMML.

ABSTRACT Patients with newly diagnosed acute myeloid leukemia (ND‐AML) derive variable survival benefit from venetoclax + hypomethylating agent (Ven‐HMA) therapy. The primary objective in the current study was to develop genetic risk models that are predictive of survival and are applicable at the time of diagnosis and after establishing treatment response. Among 400 ND‐AML patients treated with Ven‐HMA at the Mayo Clinic, 247 (62%) achieved complete remission with (CR) or without (CRi) count recovery. Multivariable analysis–derived hazard ratios (HR), including 1.8 for European LeukemiaNet (ELN) adverse karyotype, 4.7 for KMT2Ar , 1.7 for TP53 MUT , 2.6 for KRAS MUT , and 2.1 for IDH2 WT were applied to develop an HR‐weighted risk model: low, intermediate, and high; respective median survival censored for allogeneic stem cell transplant (ASCT) (3‐year survival) were “not reached” (67%), 19.1 (33%), and 7.1 months (0%). In patients achieving CR/CRi, adverse karyotype, KMT2Ar , KRAS MUT , IDH2 WT predicted inferior survival, allowing for a complementary response‐stratified risk model. The model was externally validated and was shown to be superior to the ELN 2024 risk model (AIC 179 vs. 195 and AUC 0.77 vs. 0.69). Survival was inferior with failure to achieve CR/CRi or not receiving ASCT; 3‐year survival for high‐risk with or without ASCT was 42% versus 0% ( p < 0.01); intermediate 72% versus 43% ( p = 0.06); and low‐risk 88% versus 78% ( p = 0.53). The Mayo genetic risk models offer pre‐treatment and response‐based prognostic tools for ND‐AML treated with Ven‐HMA. The current study underscores the prognostically indispensable role of achieving CR/CRi and ASCT.