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Efficacy and safety results from the primary analysis of the pivotal summit trial: Bezuclastinib in adults with non-advanced systemic mastocytosis
Rein, Lindsay , Boggs, Nathan A. , Yi, Cecilia Y. Arana , Elberink, Hanneke Oude , Radia, Deepti , Reiter, Andreas , Piris‐Villaespesa, Miguel , Dybedal, Ingunn , Panse, Jens , Vachhani, Pankit , Kirshenbaum, Arnold S. , Vaughn, Jennifer E. , Cerquozzi, Sonia , Fahrenholz, John M., Pomares, Helena , Üstün, Celalettin , Herrscher, Richard, Barète, Stéphane , Rivera, Candido E., Vadas, Peter , McCulloch, Derek, Keohane, Clodagh, Schafhausen, Philippe, Pilla, Amanda, Zhang, Jenna, Sun, Lei , Shah, Nisha , Jolin, Hina, Easton, Rachael, Sachs, Jessica, Bose, Prithviraj , Modena, Brian D. , Sabato, Vito , Hartmann, Karin , Akin, Cem , George, Tracy I. , Yi, Cecilia Arana , Oh, Stephen T. , Hunter, Anthony M. , Castells, Mariana , Livideanu, Cristina Bulai , Daele, Paul Van , Álvarez‐Twöse, Iván , Taparia, Minakshi , Mital, Andrzej , Hus, Marek , Romano, Alessandra , Lansigan, Frederick , Papayannidis, Cristina , Rondoni, Michela , Manning, Michael, Guilarte, Mar , Bernstein, Jonathan A. , Elena, Chiara , Orfali, Nina M. , Mannelli, Francesco , Shah, Nisha, Siebenhaar, Frank , DeAngelo, Daniel J.

Blood | December 4, 2025 | Volume: 146 | Issue: Supplement 1 | Pages: 80-80

10.1182/blood-2025-80 Get It

Abstract Background: Systemic mastocytosis (SM) comprises a spectrum of subtypes characterized by neoplastic mast cell (MC) infiltration of tissues and release of MC mediators. Non-advanced SM (NonAdvSM), including indolent SM (ISM), smoldering SM (SSM), and bone marrow mastocytosis (BMM) subtypes, is the most prevalent form of SM. NonAdvSM can be associated with debilitating symptomology which can significantly impair quality of life. The gain-of-function somatic KIT c.2447 C>T (p.D816V) mutation is found in up to 95% of patients with SM. Bezuclastinib (CGT9486) is an oral, potent, and selective type 1 tyrosine kinase inhibitor with activity against KIT D816V. Results from Summit (NCT05186753) Part 1 informed the recommended phase 2 dose (100 mg QD bezuclastinib) for Part 2. We report topline results from the 24-week assessment of Summit Part 2. Methods: Summit is a multi-center, randomized, double-blind, placebo (PBO)-controlled Phase 2 trial of bezuclastinib in patients with NonAdvSM who had inadequate symptom control despite best supportive care (BSC) medications. The primary endpoint was 24-week mean change from baseline in Mastocytosis Symptom Severity Daily Diary (MS2D2) total symptom score (TSS) (range 0–110), which is a fit-for-purpose patient-reported outcome measure of NonAdvSM symptom severity. Key secondary endpoints included the proportion of patients with ≥50% reduction in serum tryptase, KIT p.D816V variant allele frequency (VAF), bone marrow (BM) MC burden, and MS2D2 TSS, ≥30% TSS reduction. Patients were randomized 2:1 to receive 100mg QD bezuclastinib + BSC or PBO + BSC. Results: As of May 22, 2025, 179 patients were enrolled in Part 2: 119 were randomized to receive bezuclastinib and 60 to placebo. Patients enrolled were representative of the NonAdvSM population with moderate to severe symptoms. Median age (range) was 51 (23-78) years; 65.9% female; mean (SD) baseline MS2D2 TSS 55.6 (19.8); 82% of patients had ISM, 11% had BMM, and 7% had smoldering SSM. At baseline, median (range) KIT p.D816V VAF in whole blood, BM MC burden, and serum tryptase was 0.25% (0-34%), 10% (1-75%), and 40 (6-692) ng/mL, respectively. Bezuclastinib demonstrated statistically significant superiority to placebo on all primary and key secondary endpoints. At Week 24, bezuclastinib led to significantly greater symptom improvement vs placebo (LS mean [95% CI] MS2D2 TSS change: –24.3 [–27.6 to –21.1] vs –15.4 [–19.6 to –11.2]; placebo-adjusted difference: –8.9 points; P=0.0002). A ≥50% reduction in serum tryptase was achieved in 87.4% of bezuclastinib-treated patients vs 0% on placebo (P<0.0001). Significantly more patients receiving bezuclastinib achieved ≥50% reductions in KIT D816V VAF, serum tryptase, BM MCs (P<0.0001), MS2D2 TSS (P=0.01), and ≥30% reduction in MS2D2 TSS (P=0.0004). Most treatment-emergent adverse events (TEAEs) were low grade (gr; 70% Gr 1) and reversible. The most common TEAEs (≥10%) in any treatment group and occurring in greater frequency in the bezuclastinib arm were hair color changes (69.5% vs 5.0%), altered taste (23.7% vs 0%), nausea (22.0% vs 13.3%), increased ALT/AST (22.0% vs 6.6%), headache (17.8% vs 11.7%), alopecia (11.9% vs 3.3%), and increased ALP (10.2% vs 3.3%). TEAEs (≥10%) that occurred more often in the placebo group were diarrhea (13% vs 18%), dizziness (10% vs 12%), fatigue (7% vs 12%), and arthralgia (6% vs 15%). ALT/AST elevations ≥Gr 3 were experienced by 5.9% of patients. The only hepatic adverse events (AEs) reported were transient lab abnormalities; none required hospitalization. Treatment-related AEs requiring dose reductions occurred in 11% of patients receiving bezuclastinib. All discontinuations (5.9%) due to treatment-related AEs were due to transaminase elevations; all fully resolved. Conclusions: At 24-weeks, bezuclastinib 100 mg QD demonstrated statistically and clinically significant improvements in symptom burden and biomarkers of disease vs placebo in patients with NonAdvSM. The treatment was generally well-tolerated and effective across a population that is representative of the real-world NonAdvSM population, including SSM. These results support the use of bezuclastinib to reduce SM burden and symptoms in pts with NonAdvSM, and a potentially disease-modifying impact.
Real-world outcomes of immune checkpoint inhibitor rechallenge in patients with classical Hodgkin lymphoma
Maiocco, Giuseppe, Nishimura, Yoshito, Janda, Guneet, Han, Yiqun, Durani, Urshila, Nowakowski, Grzegorz, Paludo, Jonas, Ansell, Stephen, Abeykoon, Jithma, Maiocco, Giuseppe, Nishimura, Yoshito, Janda, Guneet, Han, Yiqun, Durani, Urshila, Nowakowski, Grzegorz, Paludo, Jonas, Ansell, Stephen, Abeykoon, Jithma

Blood | December 4, 2025 | Volume: 146 | Issue: Supplement 1 | Pages: 5395-5395

10.1182/blood-2025-5395 Get It

Abstract Background: Immune checkpoint inhibitors (ICIs) have been established as standard of care for patients with classical Hodgkin lymphoma (cHL), including relapsed or refractory (r/r) disease. However, ICIs discontinued in some patients due to treatment-related toxicities or disease progression may later be re-initiated. The outcomes of this common clinical practice of ICI re-initiation, or ‘rechallenge,‘ have not been evaluated. Here, we present real-world efficacy and safety data of ICI rechallenge in patients with cHL. Methods: We conducted a retrospective cohort study of patients with cHL treated with ICIs between 2015 and 2024 at Mayo Clinic sites. Patients were identified via institutional records using diagnostic and treatment codes. Included patients were adults ≥18 years with histologically confirmed diagnosis of cHL receiving ≥1 cycle of ICI therapy. Patients in the rechallenge cohort received a second course of ICI therapy following discontinuation of the initial ICI for any reason. The control cohort included patients with ICI discontinuation without subsequent rechallenge. Primary outcomes included progression-free survival (PFS), event-free survival (EFS), and duration of response (DOR), defined respectively as time from first ICI initiation to disease progression, time from first ICI initiation to disease progression, adverse events, treatment change, or death, and time from first recorded response per positron emission tomography–computed tomography until the occurrence of disease progression. Secondary outcomes included overall survival (OS), and incidence and severity of irAEs following ICI rechallenge. Survival outcomes were compared using propensity-score-matched (PSM) cohorts with a proportional Cox model. Results: A total of 145 patients were included. Of these, 30 (21%) underwent ICI rechallenge, while 115 (79%) received no subsequent ICI treatments. The median age was 40 years (interquartile range [IQR] 26-66). Most were male (59%), predominantly nodular sclerosis subtype (71%), Ann Arbor stage III-IV disease (65%), and ECOG ≤ 1 (96%). ICIs were utilized for r/r disease in 66%, with median 6 (IQR 4-13) cycles and follow up of 40.8 months (IQR 21.1–78.1). Patients received median 1 prior line of therapy (IQR 0-2.5). During initial ICI treatment, 34/145 patients (23%) experienced irAEs, including 17 patients (57%) in the rechallenge group and 17 (15%) in the non-rechallenge group. Most irAEs were of grade 1–2 severity, though 10 (30%) experienced grades ≥3 irAEs. irAE severity did not differ between groups. Among patients who underwent ICI rechallenge, the majority (53%) discontinued due to irAEs. The decision to pursue ICI rechallenge was driven predominantly by disease progression (63%). Among the 1:1 PSM cohorts using bone marrow transplant status and the International Prognostic Score, PFS did not significantly differ between rechallenged vs. non-rechallenged groups (HR 1.7, 95% CI 0.60–4.5, p=0.32). Similarly, no difference was noted among the groups in EFS and DOR using 1:3 PSM cohorts using the number of ICI cycles (HR 1.6, 95% CI 0.83–3.0, p = 0.16 and HR 1.6, 95% CI 0.37–7.0, p = 0.53, respectively). In the 1:1 matched cohort, ICI rechallenge was not associated with inferior OS compared to those without rechallenge (HR 1.6, 95% CI 0.48–5.4, p=0.43). irAE occurred in 20%, including pneumonitis (n=2), hepatitis (n=1), and pancreatitis (n = 1). Of the patients who had experienced irAEs during their initial ICI course, only two developed recurrent irAEs of the same type upon rechallenge, both at reduced severity. Overall, 80% of rechallenged patients did not experience any irAE with their second ICI course. Conclusions: ICI rechallenge was not associated with inferior PFS, EFS, DOR or OS compared patients without rechallenge. Among patients receiving ICI rechallenge after irAE, recurrence of same irAE was rare. ICI rechallenge may be a feasible and potentially effective strategy in selected patients with cHL.
A national cancer database study of survival trends in patients with classical Hodgkin lymphoma: Improved survival in the novel agent era
Wang, Julia, Hwang, Steven, Durani, Urshila, Thanarajasingam, Gita, Khurana, Arushi, Paludo, Jonas, Wang, Yucai, Nowakowski, Grzegorz, Habermann, Thomas, Witzig, Thomas, Ansell, Stephen, Abeykoon, Jithma, Wang, Julia, Hwang, Steven, Durani, Urshila, Thanarajasingam, Gita, Khurana, Arushi, Paludo, Jonas, Wang, Yucai, Nowakowski, Grzegorz, Habermann, Thomas, Witzig, Thomas, Ansell, Stephen, Abeykoon, Jithma

Blood | December 4, 2025 | Volume: 146 | Issue: Supplement 1 | Pages: 5399-5399

10.1182/blood-2025-5399 Get It

Abstract Introduction: Brentuximab vedotin (BV) was approved by the US FDA for relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL) in 2011 and for previously untreated advanced stage cHL in 2018. The immune checkpoint inhibitors (ICIs) nivolumab and pembrolizumab were approved for R/R cHL in 2016 and 2017, respectively. These novel agents have significantly changed the landscape of cHL management in recent years. In this study, we analyzed data from the National Cancer Database (NCDB) to investigate whether survival outcomes have improved in the novel agent era (2011 and beyond) for patients with cHL in the US. Methods: Patients diagnosed with cHL between 2004 and 2020 were identified in the NCDB. Those with missing survival data were excluded. Three treatment eras were defined based on the timing of FDA approval of novel agents: Chemo era (2004–2010), BV era (2011–2015), and ICI era (2016–2020). Patient and disease characteristics were compared using the Chi-square test. Survival analyses were conducted using the Kaplan-Meier method and Cox proportional hazards model. Results: A total of 85,488 patients with newly diagnosed cHL were identified: 36,150 in the Chemo era, 27,058 in the BV era, and 22,280 in the ICI era. Compared to the chemo era, the BV and/or ICI eras included slightly more patients aged ≥66 (17.3% vs 17.8% vs 19.5%), male (53.6% vs 54.6% vs 53.8%, p=0.042), Black (11.3% vs 12.9% vs 12.5%), Hispanic (9.0% vs 9.9% vs 10.9%), with Charlson-Deyo score ≥1 (14.2% vs 16.1% vs 17.2%), B symptoms (44.1% vs 46.9% vs 46.9%), treated at academic centers (32.4% vs 35.9% vs 36.4%), on Medicaid (9.5% vs 12.2% vs 13.7%) or Medicare (19.3% vs 20.3% vs 21.7%), and with higher income (≥4th quartile by 2008-2012 standard; 34.5% vs 34.3% vs 36.3%) (all p<0.001 except for sex, noted above). Ann Arbor stage data were not available in the ICI era. There were slightly more patients with advanced-stage disease in the BV era compared to the Chemo era (45.4% vs 40.3%, p<0.001). IPS scores were available for only 2,344 patients, with a similar distribution (0–2 vs 3–7) across the three eras (p=0.957). The median follow-up was 6.9 years (95% CI 6.9-7.0). Overall survival (OS) significantly improved in the novel agent eras: the 5-year OS rate was 79.8% (95% CI, 79.4%–81.2%) for patients diagnosed in the Chemo era, 81.9% (95% CI, 81.9%–82.4%) in the BV era, and 84.1% (95% CI, 83.5%–84.8%) in the ICI era (p<0.001). Statistically significant OS improvements were observed across all subgroups, including age (≤40: 92.8% vs 94.9% vs 96.5%, 41-65: 80.5% vs 81.8% vs 84.4%, ≥66: 41.4% vs 46.6% vs 52.7%), sex (male: 78.0% vs 80.0% vs 81.9%, female: 81.9% vs 84.1% vs 86.7%), race (White: 79.9% vs 81.6% vs 83.7%, Black: 77.2% vs 81.2% vs 84.6%, others: 84.5% vs 87.0% vs 89.3%), ethnicity (Hispanic 79.7% vs 82.3% vs 85.1%, Non-Hispanic 80.0% vs 81.9% vs 84.1%), Charlson-Deyo score (0: 83.5% vs 85.4% vs 87.9%, 1: 62.8% vs 68.2% vs 73.2%, 2: 42.5% vs 52.6% vs 58.3%, 3+: 49.0% vs 54.4% vs 51.7%), B symptoms (yes: 74.7% vs 78.9% vs 81.5%, no: 84.3% vs 85.1% vs 87.5%), treatment facility type (academic: 69.8% vs 74.0% vs 77.1%, non-academic: 66.4% vs 67.6% vs 70.2%, unknown: 92.9% vs 95.0% vs 96.5%), insurance type (private: 89.9% vs 91.2% vs 93.4%, Medicare: 46.5% vs 52.3% vs 57.2%, Medicaid: 79.1% vs 84.5% vs 87.7%) and income level (Q1: 74.1% vs 77.1% vs 81.1%, Q2 77.7% vs 80.1% vs 81.3%, Q3 79.8% vs 81.6% vs 85.2%, Q4: 82.8% vs 84.9% vs 87.0%) (all p<0.001). In multivariate Cox regression analysis adjusting for age, sex, race, ethnicity, Charlson-Deyo score, B symptoms, treatment facility type, insurance type, and income level, diagnosis in the BV era (HR = 0.856; 95% CI, 0.827–0.885; p<0.001) and ICI era (HR = 0.666; 95% CI, 0.636–0.698; p<0.001) was independently associated with improved OS compared to the Chemo era. Conclusions: In this large NCDB-based analysis, survival outcomes for patients with cHL significantly improved in the BV and ICI eras compared to the Chemo era. OS improvement was consistent across all subgroups and remained independent of age, sex, race, ethnicity, Charlson-Deyo score, B symptoms, treatment facility type, insurance type, and income level in multivariate analysis. These findings may reflect the positive impact of BV and ICIs on survival in patients with cHL.
Consensus recommendations from the 2024 International Follicular Lymphoma Scientific Workshop
Rutherford, Sarah C. , Ansell, Stephen M. , Armand, Philippe , Leonard, John P. , Smith, Sonali M. , Timmerman, John M. , Zelenetz, Andrew D. , Gutierrez, Meghan, Béguelin, Wendy , Nadel, Bertrand, Pasqualucci, Laura , LaCasce, Ann S. , Rutherford, Sarah C , Smith, Sonali M , Zelenetz, Andrew D , Béguelin, Wendy , Casulo, Carla , Cerhan, James R , Kridel, Robert , Link, Brian K , Maurer, Matthew , Radtke, Andrea J , Luttwak, Efrat , Salles, Gilles A , Pasqualucci, Laura , LaCasce, Ann Steward , Merryman, Reid W. , Nastoupil, Loretta J. , Casulo, Carla , Cerhan, James R. , Green, Michael Richard , Kahl, Brad S. , Link, Brian K. , Maurer, Matthew J. , Luttwak, Efrat , Salles, Gilles , Sehn, Laurie H.

Blood Advances | December 3, 2025 | Volume: 10 | Issue: 5 | Pages: 1591-1602

10.1182/bloodadvances.2025018079 | PMID 41337699 Get It

Abstract Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma. Although patients with FL have high response rates to therapy, most develop increasingly resistant disease. In addition, transformation into an aggressive lymphoma is associated with unfavorable outcomes. Many novel agents are under investigation, and early clinical data are encouraging. Aligning treatment with the underlying tumor biology and sequencing of therapies remain key clinical challenges. At the Lymphoma Research Foundation’s biannual 2024 Follicular Lymphoma Scientific Workshop, experts convened to discuss the role of chemotherapy in the context of new therapies, the impact of early progression on treatment sequencing, novel end points in clinical trials, disease biology and the tumor microenvironment, and new treatments on the horizon. This report focuses on updates in FL biology, first-line treatment, the role of progression of disease in 24 months, clinical trial design, and redefining cure in FL.
Prevalence and Clinical Implications of Excess Adiposity in Group 1 Pulmonary Hypertension
Reddy, Yogesh N.V. , Frantz, Robert P. , Hemnes, Anna R. , Hassoun, Paul M. , Horn, Evelyn M. , Leopold, Jane A. , Rosenzweig, Erika B. , Hill, Nicholas S. , Erzurum, Serpil C. , Beck, Gerald J. , Finet, J. Emanuel , Jellis, Christine , Mathai, Stephen C. , Group, the PVDOMICS Study, Rosenzweig, Erika B , Hill, Nicholas S , Erzurum, Serpil C , Beck, Gerald J , Finet, J Emanuel , Jellis, Christine L , Mathai, Stephen C , Tang, W H Wilson , Borlaug, Barry A , Nishimura, Rick , Frantz, Robert P , Hemnes, Anna , Horn, Evelyn M , Leopold, Jane A , Hassoun, Paul M , Rischard, Franz , Tang, W.H. Wilson , Borlaug, Barry A. , Group, the PVDOMICS Study

Circulation: Heart Failure | December 3, 2025 | Volume: 19 | Issue: 1 | Pages: No page available

10.1161/circheartfailure.125.013591 | PMID 41332382 Get It

BACKGROUND: Although obesity and insulin resistance (IR) are established risk factors for left heart dysfunction, their clinical impact in group 1 pulmonary hypertension (PH) remains unclear. We sought to determine the impact of excess adiposity versus IR on biventricular hemodynamic and functional reserve in group 1 PH. METHODS: Homeostasis model of insulin resistance and adiposity indices (body mass index [BMI], fat mass, waist circumference) were measured among group 1 patients with PH recruited to PVDOMICS (Redefining Pulmonary Hypertension Through Pulmonary Vascular Disease Phenomics). Functional capacity, and dynamic pulmonary capillary wedge pressure (PCWP) and right atrial pressure responses were compared stratified by obesity (BMI≥30 kg/m 2 ) and IR status (HOMA-IR≥2.6) using repeated-measure mixed models. RESULTS: Among patients with group 1 PH (n=418), 158 (38%) had BMI≥30 kg/m 2 (94 [60%] of whom had IR), and 260 (62%) had BMI<30 kg/m 2 (74 [28%] of whom had IR). Among those with waist circumference measurement (n=375), 287 (77%) had excess adiposity by elevated waist/height ratio, with 214 (57%) having elevated waist circumference. Patients with obesity had worse quality of life, exercise capacity and left heart remodeling, along with higher resting/dynamic PCWP, right atrial pressure and cardiac output ( P <0.0001 for all). Higher PCWP response with obesity persisted after adjusting for IR (IR-adjusted PCWP+2.5 mm Hg [95% CI, +1.4 to +3.6]; P <0.0001). All adiposity indices were consistently associated with PCWP response, but IR was not. Similar associations were observed between adiposity indices with higher right atrial pressure and cardiac output. Greater visceral adiposity as measured by body shape index (hazard ratio, 2.01 [95% CI, 1.16–3.47]; P =0.01) or weight-adjusted waist index (hazard ratio, 1.64 [95% CI, 1.10–2.46]; P =0.01) was associated with worse survival. CONCLUSIONS: Excess adiposity is common in group 1 PH, occurring in 4 out of 5 patients by the more sensitive waist/height ratio, in contrast to only 2 out of 5 patients having obesity by traditional BMI criteria. Excess adiposity is associated with higher biventricular filling pressures, cardiac output demand, worse functional status and reduced survival. These data support trials of adipose-reducing therapies in patients with group 1 PH and excess adiposity.
Safety and Efficacy in Pediatric Patients with Relapsed/Refractory Classic Hodgkin Lymphoma enrolled on an Intergroup Randomized Phase II Study of the Combinations of Ipilimumab, Nivolumab and Brentuximab Vedotin (E4412)
Wang, Victoria , Ansell, Stephen M. , Mehta-Shah, N, Amengual, Jennifer E. , Cole, Peter D. , Forlenza, Christopher J. , Jegede, O, Steidl, Christian , Natkunam, Yasodha , Scott, David W. , Kahl, Brad S. , Diefenbach, Catherine

Klinische Pädiatrie | December 3, 2025 | Volume: 237 | Issue: No issue available | Pages: No page available

10.1055/s-0045-1812988 Get It

Gene expression profiling reveals 2 overarching types of ALCL with distinct targetable biology: an LLMPP study
Feldman, Andrew L. , Dasari, Surendra, Scott, David W. , Oishi, Naoki , Hu, Guangzhen , Farinha, Pedro , Amador, Catalina , Campo, Elı́as , Cook, James R. , Fu, Kai , Greiner, Timothy C. , Iqbal, Javeed , Ondrejka, Sarah L. , Ott, G., Rosenwald, Andreas , Slack, Graham W. , Wright, George, Zeng, Yu , Yoshino, Tadashi, Wu, Xiaojun , Satou, Akira , Perry, Anamarija M. , Mou, Eric , Ko, Young Hyeh , Jiang, Liuyan , Gru, Alejandro A. , Chen, Weina , Chapman, Jennifer R. , Ansell, Stephen M. , Aljudi, Ahmed Assim , Scott, David W , Oishi, Naoki , Farinha, Pedro , Amador, Catalina , Campo, Elías , Cook, James R , Delabie, Jan , Greiner, Timothy C , Hilton, Laura K , Inghirami, Giorgio , Jaffe, Elaine S , Morin, Ryan D , Ondrejka, Sarah , Pittaluga, Stefania , Savage, Kerry J , Slager, Susan L , Wang, Hao-Wei , Wu, Xiaojun , Wilcox, Ryan A , Shi, Min , Miranda, Roberto N , Medeiros, L Jeffrey , Maurer, Matthew , Mou, Eric , Karube, Kennosuke , Gru, Alejandro , de Leval, Laurence , Chen, Weina , Cerhan, James R , Barrionuevo, Carlos , Aljudi, Ahmed Assim , Feldman, Andrew L , Iqbal, Javeed , Rimsza, Lisa M. , Chan, Wing C., Delabie, Jan , Hilton, Laura K. , Inghirami, Giorgio , Jaffe, Elaine S. , Pittaluga, Stefania , Raess, Philipp W. , Savage, Kerry J. , Slager, Susan L. , Song, Joo Y. , Wang, Hao‐Wei , Wilcox, Ryan A. , Wang, Xueju , Miranda, Roberto N. , Medeiros, L. Jeffrey , Maurer, Matthew J. , Karube, Kennosuke , Kahl, Brad S. , Jaye, David L. , Leval, Laurence de , Cerhan, James R.

Blood | December 2, 2025 | Volume: 147 | Issue: 11 | Pages: 1199-1214

10.1182/blood.2024027700 | PMID 41329859 Get It

Abstract Anaplastic large cell lymphomas (ALCLs) are CD30+ T-cell lymphomas that share pathologic features but differ in presentation, outcome, and genetics. Current classification incorporates clinical presentation and anaplastic lymphoma kinase (ALK) status but inadequately addresses molecular heterogeneity and therapeutic vulnerabilities. We studied 689 patients with ALCL in the LLMPP (Lymphoma/Leukemia Molecular Profiling Project) and performed expert consensus review, genetic subtyping (ALK, DUSP22, TP63, and triple negative), and immunohistochemistry for phosphorylated STAT3Tyr705. RNA sequencing with unsupervised gene expression profiling in 393 patients identified 2 main molecular types of ALCL that could be predicted with 91% accuracy based on the presence (type I) or absence (type II) of phosphorylated STAT3Y705 expression. Type I ALCLs included ALK+ ALCL and a subset of triple-negative ALCLs (TN-I); type II ALCLs included tumors with DUSP22 and/or TP63 rearrangements and the remaining triple-negative ALCLs (TN-II). Type I ALCLs were enriched for JAK-STAT3, whereas type II ALCLs were enriched for non–tyrosine kinase pathways, particularly epigenetic regulators such as EZH2. Immunohistochemistry showed overexpression of EZH2 and its trimethylated substrate H3K27. Prognosis in systemic ALCL was favorable for DUSP22-rearranged ALCL (5-year overall survival, 95%) and ALK+ ALCL (88%), intermediate for triple-negative ALCL (TN-I, 52% and TN-II, 37%), and poor for TP63-rearranged ALCL (0%). We introduce an integrated molecular classification that preserves currently diagnosed ALCL entities but identifies 4 molecularly distinct ALK− ALCL subtypes (DUSP22-rearranged, TP63-rearranged, TN-I, and TN-II). This classification can be easily implemented on paraffin tissue in routine practice or clinical trials, and stratifies ALCL into diagnostically, prognostically, biologically, and potentially therapeutically relevant subtypes.
Abstract 295: Prospective comparison of core and penumbra volumes from two CT perfusion quantification software packages
Wolfe, Jared , Mendis, D. A. , Beegle, Richard D. , Johnny, Shinn-Nan, Nord, Charisse A., Pahl, Elfriede , Wood, Stephen , FERNANDEZ, CLAIRE, English, S., Demaerschalk, Bart M. , Pahl, E., Wood, S., Woodhead, Zoe , Carone, Davide , Harston, George

Stroke: Vascular and Interventional Neurology | December 2, 2025 | Volume: 5 | Issue: S1 | Pages: No page available

10.1161/svi270000_295 Get It

Introduction Software packages for quantification of CT perfusion parameters allow quick visualization of perfusion deficits to support clinical decision making in acute ischemic stroke (AIS). Several packages are now commercially available for automated quantification of ischemic core, penumbra volumes, and mismatch ratios to indicate eligibility for reperfusion therapies. This study explored the agreement between two software packages, Brainomix 360 e‐CTP and Rapid CTP, in prospective, real‐world use. Methods Consecutive patients scanned for suspected stroke at three comprehensive stroke centers over 90 days from May to July 2024 were included in the study. Eligibility for the current analysis was limited to discharge diagnosis of AIS and CTP imaging processed by both Brainomix and Rapid software. Software processing was conducted in real time after image acquisition. The presence of large vessel occlusion (LVO) was determined from review of electronic medical records. CTP core (CBF<30%) and penumbra (Tmax>6s) volumes from Brainomix and Rapid were recorded for each case. Mismatch ratios were calculated (penumbra÷core volume); positive mismatch was defined according to DEFUSE‐3 criteria (core<70ml, penumbra>15ml, mismatch ratio > 1.8). The correlations and linear regressions between Brainomix and Rapid were computed for core, penumbra and mismatch ratios, and their concordance for mismatch positivity was assessed. Results 137 patients were scanned and received a final diagnosis of AIS. Of these, only 38 had imaging processed by both Brainomix and Rapid. Median age was 69 years (interquartile range: 57‐77.5y); 16 (42%) were female; 13 (34%) had LVO. Linear models between Brainomix and Rapid's outputs for CBF and Tmax volumes are shown in Figure 1a and 1b. The correlation between software outputs for CBF volume was r=0.70 (p<.001), and for Tmax volume was r=0.72 (p<.001). Mismatch ratios were calculated for the 13 cases with LVO (Figure 1c). The linear model between mismatch ratios was not significant, with four Rapid outputs showing infinite mismatch ratios (due to having CBF volumes of 0ml). Concordance between software for mismatch positivity was good; 8/13 cases showed mismatch on both softwares; 1 case showed mismatch on Brainomix only; 1 for Rapid only; and 3 cases showed mismatch on neither software. Conclusion This prospective study, despite limited sample size (N=38), showed good correlations between Brainomix 360 e‐CTP and Rapid CTP for calculation of both core and penumbra volumes. Although mismatch ratios showed less agreement, the categorization of mismatch positivity showed good concordance between software platforms. image
Abstract 245: Super‐Large‐Bore vs Large‐Bore Aspiration Catheters in Mechanical Thrombectomy: A Multicenter Propensity‐Matched Analysis
Chacon, Alexander , Inoa, Violiza , Cawley, M. F., Rai, Ansaar , Maier, Ilko , Dye, J. A., Ezzeldin, M., Matouk, Charles, Brinjikji, Waleed , Jabbour, Pascal , Almallouhi, E., Dağlıoğlu, Ergün , Spiotta, Alejandro M , Grossberg, Jonathan A , Chacon, A., Alawieh, Ali , Motiwala, Mustafa , Arthur, Adam Stephen , Cawley, M., Howard, Brian M , Siddiqui, F., Alaraj, Ali , Romano, Daniele Giuseppe , Fiorella, David , Dye, J., Wolfe, Stacey Q , Mascitelli, Justin R , Fragata, Isabel , Limaye, Kaustubh , Ogilvy, Christopher S. , Jabbour, Pascal , Almallouhi, Eyad , Park, M. S., Navía, Pedro , Grandhi, Ramesh , Altschul, David , Schirmer, Clemens M. , Paul, Alexandra R , Mokin, Maxim , Goyal, Nitin

Stroke: Vascular and Interventional Neurology | December 2, 2025 | Volume: 5 | Issue: S1 | Pages: No page available

10.1161/svi270000_245 Get It

Background Contact aspiration remains a frontline approach for mechanical thrombectomy (MT) in acute ischemic stroke (AIS). Early evidence correlates catheter size with procedural efficiency and clinical outcomes. Larger‐bore (LB) aspiration catheters may enhance clot ingestion, increase aspiration force, and facilitate faster and more complete recanalization. However, the transition from standard LB catheters (0.068‐0.072″) to super‐large‐bore (SLB, ≥0.080″) devices has raised questions regarding both safety and clinical benefit. Although the use of SLB catheters is increasing, comparative data on their performance versus LB catheters remain limited. This study aims to evaluate the safety and efficacy of SLB compared with LB catheters including data from a large multicenter international registry. Methods We retrospectively analyzed patients with AIS due to LVO treated at 46 international stroke centers between January 2013 and June 2025. Among eligible patients, propensity score matching (PSM) at a 5:1 ratio was used to balance baseline characteristics between those treated with standard LB catheters and those treated with SLB catheters. Safety endpoints included intraprocedural complications, symptomatic intracranial hemorrhage (sICH), distal embolization, and 90‐day mortality. Efficacy endpoints included functional independence at 90 days (modified Rankin Scale [mRS] 0‐2), successful recanalization (TICI ≥2b), first‐pass effect (TICI ≥2b on the first aspiration attempt), and procedural timing to TICI2b. Results A total of 3,100 patients were included (LB n=3,024; SLB n=67). After PSM (LB n=335; SLB n=67), safety outcomes were comparable between groups in terms of intraprocedural complications occurred (p=0.5), sICH (p>0.9), embolization to new territory (p=0.2), and 90‐day mortality (p>0.9). Efficacy outcomes were similarly consistent for functional independence (mRS 0‐2) (p>0.9), successful recanalization (p>0.9), first‐pass effect (p=0.5), and time to TICI ≥2b (27.6 vs. 24.5 minutes; p=0.9). These findings remained consistent in the subgroup with ICA and M1 occlusions, with no significant differences in safety (intraprocedural complications [p=0.4], sICH [p>0.9], embolization to new territory [p=0.6], or 90‐day mortality [p>0.9], nor in efficacy outcomes (functional independence at 90 days [p>0.9], successful recanalization [p=0.9], first‐pass effect [p=0.6], and time to TICI ≥2b [p=0.9]). Conclusion In this large multicenter analysis, the use of SLB aspiration catheters demonstrated comparable safety and efficacy to standard LB catheters for MT in AIS. Despite theoretical advantages in aspiration dynamics, SLB devices did not confer significant procedural or clinical benefit over LB catheters. These findings suggest that while SLB catheters are a feasible alternative, technical and clinical outcomes remain comparable to LB catheters. Further prospective studies are warranted to clarify potential clinical advantages. image
Abstract 073: Validation of the EMVision emu™ Brain Scanner for Intracranial Hemorrhage Detection in Suspected Stroke: Protocol for an International Diagnostic Performance Study
Shoirah, Hazem , Wight, C., Khandan, Nouna, Khandan, F., DeLeacy, R., Davis, Stephen C. , Santos, Angela Dos , Cordato, Dennis , Gusdon, Aaron M. , Freeman, William D. , Xu, Z., Crozier‬, ‪Stuart , DeLeacy, R., Donnan, Geoffrey A. , Davis, S.

Stroke: Vascular and Interventional Neurology | December 2, 2025 | Volume: 5 | Issue: S1 | Pages: No page available

10.1161/svi270000_073 Get It

Background Rapid stroke type identification is essential for time‐sensitive interventions, yet timely neuroimaging remains limited, especially in pre‐hospital and resource‐constrained settings. The EMVision emu™ Brain Scanner is a portable neurodiagnostic device using non‐ionizing electromagnetic signals to distinguish stroke subtypes. In an Australian prevalidation study enrolling 277 suspected stroke patients, it demonstrated diagnostic accuracy with sensitivity and specificity of 92% and 85% for hemorrhagic and 95% and 80% for ischemic strokes, respectively. Case studies and image reconstructions provided (figures 1 and 2). This follow‐up study aims to validate the diagnostic performance of emu™ for detecting intracranial hemorrhage in an international cohort, targeting ≥80% sensitivity and specificity. Methods A prospective, multi‐center, international, paired diagnostic accuracy study, with 4 US sites and 2 Australian sites. It will enroll 300 patients presenting within 12 hours of stroke onset. Patients will be stratified into two arms: intracranial hemorrhage, and ischemic stroke, TIA, or stroke mimic. Participants will undergo standard imaging, followed by non‐invasive scan by the emu™ device. Ground‐truth diagnoses will be adjudicated by a blinded expert panel. The primary endpoints are the sensitivity and specificity of the emu™ device for detecting hemorrhage, calculated against the reference standard. Statistical inference will rely on whether the lower bound of the 95% confidence interval for sensitivity and specificity exceeds 80%. Results First Australian and US enrollments occurred on June 11, 2025, and July 3, 2025, respectively. Latest progress in the study will be presented at the time of conference. Conclusion This is the first international validation study of a portable electromagnetic brain scanner for intracranial hemorrhage detection; a novel, non‐ionizing, diagnostic tool that can revolutionize acute stroke triage, enabling earlier treatment decisions, improved workflows, and equitable access to neuroimaging. image image