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Background To compare the effectiveness of glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) versus bariatric surgery on cardiovascular outcomes in patients with heart failure (HF) with preserved ejection fraction and obesity. Methods Using the TriNetX research network, we conducted a retrospective cohort study of adults (aged ≥18 years) with HF with preserved ejection fraction and obesity (body mass index >30 kg/m 2 ) from 2017 to 2022. Patients were categorized into 2 cohorts: those receiving GLP‐1 RAs (semaglutide or tirzepatide) and those who underwent bariatric surgery. Propensity score matching (1:1) was used to balance baseline characteristics. Primary outcomes included acute HF events and all‐cause hospitalizations. Secondary outcomes included all‐cause death, myocardial infarction, stroke, and follow‐up body mass index. Cox proportional hazard models were used to estimate hazard ratios (HRs). Results A total of 2747 patients were included per cohort (mean age, 68 years). GLP‐1 RA therapy was associated with lower incidence of acute HF events (38.9% versus 44.6%; HR, 0.78 [95% CI, 0.72–0.85]), all‐cause death (11.1% versus 14.8%; HR, 0.71 [95% CI, 0.61–0.82]), and all‐cause hospitalizations (66.4% versus 77.3%; HR, 0.62 [95% CI, 0.58–0.66]). Rates of myocardial infarction (13.8% versus 13.4%; HR 0.99 [0.86–1.14]) and stroke (9.7% versus 10.7%; HR, 0.87 [0.74–1.02]) were similar between groups. Mean body mass index at follow‐up was 38.0 in the GLP‐1 RA cohort versus 37.7 after bariatric surgery ( P =0.34). Hemoglobin A 1c at follow‐up was higher in the GLP‐1 RA group (7.4 versus 6.8; P <0.001). Conclusions In patients with HF with preserved ejection fraction and obesity, GLP‐1 RA therapy was associated with improved outcomes compared with bariatric surgery, supporting the need for prospective trials to evaluate GLP‐1 RAs as a therapeutic alternative.

Abstract Multiple myeloma is a malignancy of clonally expanded plasma cells shaped by complex interactions with the immune microenvironment (IME). To investigate immune correlates of treatment response and disease progression, we conducted multi-omics profiling including CD138neg single-cell RNA sequencing of 243 bone marrow samples from 102 patients (631,226 cells) and CD138pos bulk RNA and whole-genome sequencing from 209 samples. In longitudinal analyses, interferon-γ signaling associated with markers of impaired T-cell memory after autologous stem cell transplant, whereas naïve B-cell abundance and immunoglobulin diversity correlated with improved progression-free survival (HR = 0.48; P = 2.3e−4). At disease progression, multiple myeloma cells upregulated cancer–testis antigens (CTAg) and immune effector genes, with concurrent B-cell depletion, enrichment of myeloid-derived suppressor cell expression, and phenotypic T-cell exhaustion. These findings highlight dynamic immune–tumor interactions, identifying naïve B-cell reconstitution as a biomarker of durable response and CTAgs as potential targets for high-risk disease at progression. Significance: Longitudinal profiling of multiple myeloma and the IME revealed dynamic immune–tumor interactions across the disease course. Altered expression in CD8+ T cells limited memory phenotype after transplant, whereas naïve B-cell recovery associated with sustained treatment response. At progression, CTAg expression associated with immunosuppression, revealing novel mechanisms of immune dysregulation.

Abstract Immune checkpoint inhibitor–associated immune thrombocytopenia (ICI-ITP) has been described in case reports and small case series, but comprehensive data on its incidence, risk factors, clinical features, treatment, and outcomes are lacking. We reviewed medical records of all adults initiating ICI therapy between 2016 and 2023 at 29 US hospitals across 7 major cancer centers to identify patients with ICI-ITP. Multivariable logistic regression was used to identify risk factors, and Cox modeling was performed to assess the association between ICI-ITP, its severity, and mortality. Among 86 467 patients, ICI-ITP occurred in 214 (0.25%). Independent risk factors included lower baseline platelet count, combination ICI therapy, stage IV cancer, and additional immune-related adverse events. ICI-ITP occurred at a median of 8 weeks (interquartile range [IQR], 4-18) after ICI initiation, with a median nadir platelet count of 41 × 109/L (IQR, 17 × 109/L to 64 × 109/L). Patients were treated with glucocorticoids (n = 106 [49.5%]), immune globulin (n = 39 [18.2%]), and thrombopoietin receptor agonists (n = 29 [13.6%]). Recovery occurred in 161 patients (75.2%) at a median of 2.3 weeks (IQR, 1.0-5.3). Of 76 patients rechallenged with ICIs, 23 (30.3%) developed recurrent ICI-ITP. ICI-ITP and its severity were associated with higher all-cause mortality, with a nearly threefold increase in risk among patients with severe ICI-ITP than those without ICI-ITP (adjusted hazard ratio, 2.96 [95% confidence interval, 2.14-4.08]). These findings establish ICI-ITP as a rare but clinically significant complication of ICI therapy, provide, to our knowledge, the first large-scale description of its risk factors and clinical course, and underscore the importance of timely recognition and management.

Introduction: This study investigated the association between capitate morphology and the success rates of non-vascularized bone graft (NVBG) and vascularized bone graft (VBG) operations for scaphoid nonunion. Methods: We retrospectively analysed 213 patients with established scaphoid non-union who underwent either non-vascularized bone graft ( n = 75) or vascularized bone graft ( n = 138). We analysed risk factors, including demographics, medical history, implant type, previous surgery, bone graft donor site and capitate morphology for their association with treatment outcome. We also assessed the relationship between capitate and scaphoid morphology in the uninjured wrists of 31 patients. Results: The overall success rate was 81% for NVBG and 86% for VBG, with no significant difference. For NVBG, Type II capitate, age 40 or older and tobacco use were significant risk factors for failure. For VBG, only previous surgery was a significant risk factor. In uninjured wrists, a Type II capitate was associated with a significantly thinner scaphoid waist and a lower waist index than a Type I capitate. Conclusion: Our study introduces a new radiographic classification of capitate morphology and establishes its significant association with scaphoid morphology. Beyond traditional factors, capitate morphology can help to assess scaphoid morphology and potentially infer vascularity, aiding the selection of the most appropriate bone graft type for treating scaphoid non-union. Level of evidence: III

Background: Endometriosis affects an estimated 10% of reproductive-aged women and is associated with increased ovarian cancer risk. While BRCA1/2 mutations are established risk factors for ovarian cancer, their association with endometriosis remains unclear. This study aimed to characterize the prevalence and clinical features of endometriosis within a large cohort of BRCA mutation carriers. Methods: A descriptive analysis was conducted using data from a multi-center longitudinal cohort of women with pathogenic BRCA variants. Reproductive history and related factors were collected through self-reported questionnaires and compared. Results: Among 16,950 BRCA carriers, the prevalence of endometriosis was 2.4%. Compared to BRCA carriers without endometriosis, those with endometriosis were more likely to carry a BRCA2 mutation, have post-secondary education, and experience earlier menarche. BRCA carriers with endometriosis had a lower ovarian cancer prevalence than those without (10% vs. 15%, p < 0.001). Conclusions: This is the first study of this scale to report the prevalence of endometriosis among BRCA mutation carriers, which was lower than previously reported in the general population. The association between endometriosis and ovarian cancer does not appear to be generalizable to this population. Further prospective studies are warranted to clarify this association among BRCA mutation carriers.

Abstract Introduction: Adult T-cell leukemia/lymphoma (ATLL) is a rare blood disorder associated with human T-cell leukemia virus type 1 (HTLV-1) infection. It is generally categorized into four subtypes: smoldering, chronic, lymphoma, and acute. Given the heterogeneity of these subtypes, there is a significant difference in outcomes. Robust and contemporary epidemiological data are lacking for this rare disorder. We present a retrospective cohort study of patients with ATLL, utilizing the National Cancer Database (NCDB) to better characterize the epidemiology and survival trends in the United States. Methods: This is a retrospective cohort study using the NCDB to identify ATLL cases diagnosed from 2004-2020. Descriptive statistics summarized baseline characteristics, while chi-square tests assessed group differences. Overall survival (OS) was estimated using Kaplan-Meier analysis and compared using log-rank tests. Multivariable Cox proportional hazards models identified independent prognostic factors (p &lt; 0.05 considered significant). Results: A total of 635 patients were identified with ATLL, including 344 (54%) males and 291 (46%) females, with a median age at diagnosis of 59 years (range: 19-90). Most patients came from the Middle Atlantic (NY, NJ, PA) region (33%), followed by the South Atlantic (DC, DE, FL, GA, MD, NC, SC, VA, WV) region (20%) and the East North Central (IL, IN, MI, OH, WI) region (8%). Of the 635 patients, 335 (52%) were Black, 247 (39%) White, and 26 (4%) Asian. Sixty-five (10%) patients were of Hispanic origin. Over half of patients with ATLL (54%) had a median income below $46,000. International Prognostic Index (IPI) score was only available for 16 patients: three (19%) patients were in the high-risk group, 7 (43%) in the high-intermediate group, and 6 (37.5%) in the low-intermediate group. Treatment groups included 357 (56%) patients treated with chemotherapy and 29 (4.5%) who received radiation therapy. Thirty-three (5%) patients underwent hematopoietic stem cell transplant (HSCT), including 27 autologous and 16 allogeneic transplants. The median survival time in the cohort was 9 months (95% CI 7.3-10.7). One-year OS rate in the cohort was 43%, while 2-year and 5-year OS rates were 31% and 23.5%, respectively. Patients over the age of 65 had a significantly shorter median OS than those under 65 (4 vs. 11 months, p=0.001) and were significantly less likely to undergo HSCT (p&lt; 0.001). Black patients had significantly shorter median OS compared to White patients (7.8 months vs 13.3 months, p=0.014), despite similar treatment rates with chemotherapy and HSCT. Median OS appeared to improve over time, from 8 months in patients diagnosed between 2004-2009 to 10 months for those diagnosed between 2016-2020, although this was not statistically significant (p=0.145). Treatment with allogeneic HSCT was associated with significantly prolonged median survival, compared to those who did not receive transplant (50 months vs. 7 months, p&lt;0.05). Additionally, receiving chemotherapy and/or radiation compared to not receiving treatment was also associated with significantly prolonged median survival (p&lt;0.05). Patients treated in the Middle Atlantic region had a median survival of 8.8 months, compared to 23.2 months in the West South Central (AR, LA, OK, TX) region (p&lt; 0.001). Increased education and income levels were not significantly associated with improved survival. There were no significant differences in survival between males and females. Conclusions: We provide contemporary estimates on the epidemiology of ATLL. Factors associated with improved prognosis included undergoing HSCT, radiation, or chemotherapy. We report that increased age and Black race are negative prognostic factors. Regional differences in incidence and survival persist in the US. Our study findings underscore the need for increasing access to treatment, including HSCT for those who are good candidates. Additionally, there remains work to be done to address racial disparities in the care of patients with ATLL.

Abstract Introduction: First-line therapy for mantle cell lymphoma (MCL) represents a critical opportunity for clinical benefit via sustained complete response. Multitargeted combinations, including optimized chemotherapy with novel agents targeted to MCL, may best address the biologic heterogeneity of this disease. Building on prior experience using modified VR-CAP and R-cytarabine, we enhanced this regimen by adding acalabrutinib while reducing cytarabine, aiming for improved efficacy and safety without impeding stem cell collection. To evaluate this regimen, we conducted a phase 2 multicenter trial at four centers in the Academic and Community Cancer Research United (ACCRU) network. Methods: CARiBOU (ACCRU-LY-1804) employs alternating VR-CAP and R-cytarabine with continuous acalabrutinib, in six 21-day cycles, for previously untreated MCL. Eligible patients (pts) were at least 18 years old with adequate organ function, measurable disease, no CNS involvement; and were ASCT-eligible per investigator. VR-CAP (cycles 1, 3, and 5) employed bortezomib 1.3 mg/m² subcutaneously days 1,8, and 15; rituximab 375 mg/m² day 1; cyclophosphamide 750 mg/m² day 1; doxorubicin 50 mg/m2 day 1; and prednisone 100 mg PO days 1-5. Cycles 2,4, and 6 used outpatient rituximab with cytarabine at 3 g/m² x 2 daily doses in the first 5 pts, after which the dose was reduced to 2 gm/m2 x 2 daily doses due to thrombocytopenia. Acalabrutinib 100 mg p.o. twice daily was given continuously but held for grade 4 thrombocytopenia or clinically significant toxicity. Growth factors and prophylactic antimicrobials were required. Responses were assessed after six cycles using FDG PET/CT, bone marrow aspirate/biopsy (BM Bx), and endoscopy when indicated (Lugano 2014). The primary endpoint was complete metabolic response (CMR) rate at end of treatment (EOT). Secondary endpoints included safety, feasibility of stem cell collection, proportion proceeding to ASCT, and progression-free (PFS) and overall survival (OS). Peripheral blood measurable residual disease (MRD) was evaluated using the ClonoSEQ assay (Adaptive Biotechnologies). A Simon two-stage design was used, targeting a CMR rate ≥ 70% versus a null rate of 50%, with a total sample size of 39 evaluable pts. Results: 41 pts were accrued from October 2021 through May 2025, 37 of whom completed all 6 cycles and are evaluable for response; two are still on therapy, and two discontinued therapy early for toxicity. Median age was 63 years (range 41-73), 22% were female, and 85% were White. MIPI risk groups were low (44%), intermediate (39%), and high (17%), and Ki-67 was ≥ 30% in 54% of pts. Three pts (7%) had known TP53 mutations by sequencing. At EOT, the CMR rate was 85.3% among all pts (35/41; 95% CI 67.9%-92.9%), or 94.5% among evaluable pts (35/37). BM Bx was performed in 31 pts at EOT, 30 of which (96.8%) were negative for MCL. Undetectable peripheral blood MRD using a 10^6 threshold (uMRD6) was achieved at EOT in 78.1% (25/32) of tested pts, and 93.8% (30/32) achieved uMRD5. Nine of 41 pts underwent ASCT; no patient failed stem cell collection. Maintenance therapy was not protocol-defined but included rituximab in 91.9% of pts and a BTK inhibitor in 21.6% of pts. With a median follow-up of 16.7 months, PFS and OS rates at 18 months were 76.7% (95% CI: 60.7%-96.9%) and 95.5% (95% CI: 87.1%-100%). Toxicities were primarily hematologic. Grade 3+ toxicities included thrombocytopenia (66.6%), neutropenia (28.2%), and anemia (25.6%). Grade 3+ febrile neutropenia was observed in 10.2% of pts. Peripheral neuropathy was seen in 20.5% of pts and all grade 1-2. Bleeding events included purpura in 2 pts (5.2%) and epistaxis in 1 patient (2.6%). One case of atrial fibrillation was observed. Eighteen pts required temporary dose hold of acalabrutinib for toxicity (mainly thrombocytopenia), and 2 had acalabrutinib dose reductions. Serious adverse events occurred in 6 pts, and no treatment-related deaths occurred. Conclusions: CARiBOU is an efficient, highly effective outpatient regimen for 1st line MCL, employing intermediate dose cytarabine with continuous acalabrutinib. With supportive care and platelet monitoring, this approach safely yielded high rates of CMR and uMRD6, supporting multitargeted induction therapy for appropriate pts with untreated MCL.

Abstract E1910 evaluated the addition of blinatumomab to chemotherapy in adults with B-acute lymphoblastic leukemia (ALL). The addition of blinatumomab in patients (pts) with measurable residual disease (MRD) negative (neg) B-ALL significantly improved both relapse-free and overall survival (NEJM 2024; 391: 320-33)1. Given the increasing use of blinatumomab and the E1910 backbone chemotherapy regimen, we evaluated &gt; Grade 3 toxicities on this trial in further detail. We assessed toxicity among the MRD-neg pts by age, gender, body mass index (BMI), combined cytogenetic-molecular risk, and number of cycles of blinatumomab received. We also evaluated toxicities during induction since this trial used a modified chemotherapy backbone. Methods: The eligibility, combined cytogenetic-molecular risk, and treatment have been previously described.1 All toxicities were &gt; Grade 3 by CTCAE version 4 with at least a possible relationship to treatment. Descriptive statistics were used to summarize the occurrence and rates of toxicities and Fisher's exact test was used to compare differences in proportions between groups. Analysis of induction included all pts who started treatment. Analysis of Step 3 toxicities included MRD-neg pts who started treatment on the blinatumomab (n=111) or chemotherapy only arm (n=112). Results: Pt characteristics: For induction (n=488), median age was 51 years (yrs) (range 30-70); 48.6% female. Combined cytogenetic-molecular risk: favorable (13.5%); intermediate (12.9%); no risk assigned (16.2%); unfavorable (57.4%). For induction, we compared toxicities for E1910 (n=488) to pts treated on a prior young adult study (n=289) (C10403) (Blood Adv 2021; 5(2): 504-12). The incidence of hyperglycemia (8% vs. 31.1%, p&lt; 0.001), aspartate aminotransferase (AST) increase (6.1% vs. 12.8%, p=0.002), alanine aminotransferase increase (ALT) (11.7% vs. 28.7%, p&lt; 0.001), and hyperbilirubinemia (11% vs. 19%, p=0.002) were significantly lower in E1910 pts. The incidence of pancreatitis (1.8%), thromboembolic events (4.5%), and febrile neutropenia (25.4%) in E1910 was similar to C10403. Toxicities in the MRD-neg pts in the blinatumomab arm (n=111): Despite a high incidence of neutropenia (74.8%) and thrombocytopenia (55.9%) in Step 3, there was a relatively low incidence of sepsis (7.2%), bacteremia (1.8%), cytokine release syndrome (CRS) (3.6%) and neurologic adverse events (0-6.3%). There was a higher incidence of neurological or psychiatric events in the blinatumomab arm (23%) versus chemotherapy arm (5%) (p &lt; 0.001) when all events were combined. There was a numerically higher incidence of ataxia (4.4% vs. %, p=0.16) and dysphasia (11.1% vs. 3%, p=0.12) in pts &gt; 55 yrs and a higher incidence of neutropenia (80.3% vs. 66.7%, p=0.12) and thrombocytopenia (62.1% vs. 46.7%, p=0.12) in the younger pts (age &lt; 55 yrs). In pts with a BMI &lt; 30 kg/m2 (vs. &gt; 30 kg/m2), there was a significantly higher incidence of leukopenia (51.7% vs. 26.4%, p=0.007) and thrombocytopenia (65.5% vs. 45.3%, p=0.037). However, this did not translate into an increased incidence of bleeding or infectious complications. By gender, females had a higher numerical incidence of AST increase (8.8% vs. 0%, p=0.057) and CRS (7% vs. 0% p=0.12); whereas males had a higher incidence of catheter- related infections (7.4% vs. 0%, p=0.05) and hyperglycemia (11.1% vs. 3.5%, p=0.16). A little more than half (56.8%) of pts received 4 cycles of blinatumomab with the remainder of pts receiving 1 (10.8%), 2 (28.8%), or 3 cycles (3.6%). Pts receiving 3-4 cycles of blinatumomab vs. 1-2 cycles of blinatumomab had a statistically higher incidence of anemia (38.8% vs. 6.8%, p&lt; 0.001), neutropenia (98.5% vs. 38.6%, p&lt; 0.001), and thrombocytopenia (83.6% vs. 13.6%, p&lt; 0.001), likely related to being on treatment for a longer period of time. Conclusions: Blinatumomab was well tolerated with no significant toxicity differences noted by age, gender, or number of cycles of blinatumomab received. Pts with a lower BMI did have an increased incidence of leukopenia and thrombocytopenia, possibly related to flat dosing of the drug. However, this did not translate into increased complications. Toxicites during induction were notably few, which suggests that this backbone with age adjustments may serve as a good backbone for future trials. Blinatumomab is being evaluated with low dose chemotherapy and other targeted agents in ongoing trials.

Abstract Background: MyeloMATCH is an NCI-sponsored initiative for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) employing a Master Screening and Reassessment Protocol (MSRP) to assign patients (pts) to a pt and disease biology-specific clinical trial. Several trials evaluating initial therapies are currently open, while subsequent trials dedicated to eradicating measurable residual disease during consolidation and including stem cell transplant are being developed. A pt enrolled at diagnosis may be followed longitudinally and be eligible for trials in sequential tiers throughout the treatment course. We report key data concerning the first cohort of pts enrolled on the MSRP. Methods: After pts with suspected AML or MDS consent for the MSRP, blood and marrow are sent to the myeloMATCH Molecular Diagnostics Network (MDNet) of central CLIA labs operating under a single Investigational Device Exemption to rapidly define molecular, cytogenetic, and immunophenotypic characteristics. These data are catalogued by a bioinformatics team (MATCHBox) and reviewed daily to assign participants to an available trial based on pt and disease features. A Tier Advancement Pathway (TAP) allows standard of care therapy with potential for assignment to subsequent myeloMATCH trials. Since activation in May 2024, 550 patients age≥18 were enrolled on the MSRP from 76 institutions: 48 Academic, 14 NCORP, 11 community, 3 VA. There are currently 4 open randomized AML trials (≥age 60 or unfit with mutant FLT3, ≥age 60 IDH2 mutant AML, fit age&lt;60 ELN 2017 intermediate-risk AML, fit age&lt;60 ELN 2017 adverse risk) and 1 MDS trial(IDH2 mutant). Patients not eligible for an open protocol were assigned to TAP. Results: Of the 550 pts consented, 491 completed screening assays; 49 had no or incomplete samples; 10 withdrew before completed analysis. Median cytogenetic turnaround time (TAT) was 69 hours (91% within 72 hours), and median Next Generation Sequencing (NGS) TAT from receipt was 49 hours (95% within 72 hours). Seventy-six pts (of 491 with assay data) were not assigned due to non-AML or non-MDS diagnoses, the most common being: B-ALL [n=11], MPN [9], benign marrow [9], APML [7], and MPAL [6]. The AML/MDS verified cohort was 415 pts, 366 (89.2%) patients with AML (45% age &lt;60) and 49 (11.8%) with MDS. The median age at screening was 63 years (range:18-95) and 186 (45%) were female. Eighty-two percent identified as White, 7.5% Black, 3% Asian, 7% unknown, and 9% as Hispanic. The most frequent mutations in the AML pts were NPM1 (24.0%), DNMT3A (22.7%), TET2 (19.9%), NRAS (18.0%), FLT3 (18.0% ITD, TKD 7.1%), TP53 (14.5%), and CEBPA (8.7%); IDH1/2 mutation rates were 8.2% and 13.7%, respectively. Co-mutations include FLT3/NPM1 (9.8%), NPM1/IDH2 (4.4%), IDH1/2 and any RAS (3.8%). Karyotypes were normal in 40.4%, complex 20.8%, inv(16) 6.0%, MLL/KMT2A 4.6% and t(8;21) 1.9%. 29% had favorable risk disease, 29% intermediate, and 42% adverse (ELN 2017). In MDS, mutations included: TP53 (36.7%), RUNX1 (20.4%) ASXL1 (20.4%), TET2 (18.4%), spliceosome mutations (SRSF2, SF3B1, U2AF1 and ZRSR2, 28.6%) andIDH1/2 in 4.1% and 6.1%, respectively. Karyotypes were normal in 24.5%; complex in 40.8%. By IPSS-R, 2.4% were low, 73.8% intermediate, 2.4% high, and 21.4% very high risk. 82/415 (20%) pts were assigned to initial therapy protocol, with an increase in assignment rate to 44% in the most recent two months. 71/415 pts (16%) were enrolled in one of the MyeloMATCH studies. Three-hundred forty-four pts (80%) were assigned and enrolled to TAP (296 AML, 48 MDS) for potential assignment to subsequent tier trials. In the TAP AML pts, 99 (33%) have completed initial treatment, including intensive chemotherapy (IC) in 62% of pts and hypomethylating agents/venetoclax (HMA/VEN) in 38%. In pts &lt;60 years of age, 87% received IC v. 13% with HMA/VEN, in &gt;60 34% IC v. 66% HMA/VEN and in age 60-75 42% IC v. 58% HMA/Ven. Conclusion: MyeloMATCH has screened over 500 pts from academic and community sites in the US and Canada in 14 months, meeting the TAT goal of sample acquisition to results of &lt;72 hours. Assignment to treatment protocols has substantially increased recently. As additional trials open (12 in development) we expect the percentage of pts enrolled on MSRP who go on to therapeutic trials will markedly increase, thereby allowing a personalized medicine approach for a broad group of US and Canadian adult pts with AML and MDS.

Abstract Introduction: The prognosis of patients (pts) with histological transformation (HT) of Waldenström macroglobulinemia (WM) remains dismal with standard chemoimmunotherapy. CD19-targeted chimeric antigen receptor T-cell therapies (CAR-T) can lead to durable responses in relapsed/refractory (R/R) large B-cell lymphoma (LBCL) and are approved in the second or third line settings. Pts with HT-WM were largely excluded from CAR-T trials. We previously reported high response rates in a series of 23 pts. The aim of the present study was to evaluate a larger cohort of pts with R/R HT-WM treated with CAR-T with a longer follow-up. Methods: We performed a multicenter retrospective study of pts with biopsy-proven transformed WM/lymphoplasmacytic lymphoma treated with CAR-T in the French DESCAR-T registry (NCT04328298), 4 centers from ECWM and 4 US centers. This study includes updated data from previously published cases (Durot et al, Blood, 2024). Responses were assessed according to the Lugano 2014 criteria. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded according to the ASTCT 2019 consensus criteria. Hematological toxicity and infections were graded according to the NCI CTCAE (version 5.0). Progression-free survival (PFS) and overall survival (OS) were calculated from the date of CAR-T infusion and estimated using the Kaplan-Meier method. Results: 50 pts were included (39 from DESCAR-T centers, 7 from US centers and 4 from ECWM centers). Median age was 60 (range: 32-72) and 68 (range: 42-82) years at WM diagnosis and CAR-T infusion, respectively. MYD88L265P and CXCR4 mutations were present in 79% (23/29) and 15% (2/13) of patients with available data, respectively. The median time from WM to HT diagnosis was 5.3 years (range: 0-32). Median prior lines of therapy was 1 (range: 0-9) for WM and 2 for HT (range: 0-4). Twenty (40%) pts previously received a BTK inhibitor for WM or HT, 12 (24%) underwent prior autologous SCT and 1 pt allogeneic SCT. 40% of pts presented primary refractory disease and 44% were refractory to last treatment before CAR-T. 40 pts (80%) received bridging therapy, of whom 17 (44%) responded (7 complete responses (CR)). 35 (70%), 10 (20%), and 5 (10%) pts received axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), and lisocabtagene maraleucel (liso-cel), respectively. The best overall response rate (ORR) was 94%, with 44 (88%) pts reaching CR. With a median follow-up of 25.7 months (range: 1-69) from CAR-T infusion, the median PFS was 1.2 years (95% CI: 0.5-4.5) and median OS was 4.2 years (95% CI: 1.2-not reached). Median duration of response was 1.5 years (95% CI: 0.4-4.4), with a median of 4 years (95% CI: 1.5-NR) for pts still in CR at 6 months after CAR-T. 22 pts experienced relapse/progression after CAR-T, 19 related to LBCL and 3 to WM. Median survival after relapse was 7.9 months (95% CI: 3.8-25.3). At LBCL relapse after CAR-T, salvage therapy consisted of CD20xCD3 bispecific antibodies for 9 pts, lenalidomide +/- anti-CD20 or anti-CD19 antibody for 6 pts, and BTKi for 3 pts. Among 19 pts who died, 14 (74%) were due to progressive disease and 5 (26%) from infections. 37 (76%) pts experienced CRS, including 2 (4%) grade 3 events, and 22 (45%) had ICANS, with 2 (4%) ≥ grade 3 events. 17 (35%) pts presented infections, including 12 ≥ grade 3. 21 (43%) pts developed ≥ grade 3 prolonged cytopenias (ie, not resolved within 30 days post infusion). CNS involvement due to LBCL was present in 11 pts (22%) at the time of CAR-T. 6 of them had ICANS, with 1 grade 4. The best ORR was 91% (best CR 91%). Only 1 patient did not obtain a response, with stable disease at 1 month and progression at 3 months. The median PFS was 1.2 year (95% CI: 0.2-NR) and median OS was NR (95% CI: 0.5-NR). On univariate analysis, only elevated LDH was correlated with worse PFS (HR 2.5, p=0.04) and OS (HR 3.3, p=0.04). Other variables, including number of prior lines of therapy, MYD88 mutation status, primary refractory disease, refractory to last treatment, CNS involvement before CAR-T, response after bridging therapy and type of CAR-T received, were not associated with inferior PFS or OS. Conclusion: This cohort represents the largest series of pts with transformed WM treated with anti-CD19 CAR-T. We confirm the high efficacy previously reported with an acceptable safety profile, including for pts with CNS involvement due to LBCL at CAR-T infusion.