Hematological Oncology最新文献

{"title":"CD19 CAR-T CELL THERAPY IN RELAPSED/REFRACTORY SOLID ORGAN TRANSPLANT-RELATED LYMPHOPROLIFERATION: A LYSA ANALYSIS OF THE FRENCH COHORT DESCAR-T","authors":"E. Corvilain, R. Di blasi, C. Thieblemont, M. Cheminant, B. Guffroy, J. Decroocq, A. Campidelli, M. Rubio, F. Claves, S. Carras, M. Mothy, V. Dupont, R. Houot, S. Choquet","doi":"10.1002/hon.70094_381","DOIUrl":"https://doi.org/10.1002/hon.70094_381","url":null,"abstract":"<p><b>Introduction:</b> Post-transplant lymphoproliferative disorder (PTLD) is a rare but severe complication of solid organ transplantation (SOT). First-line treatment typically involves reducing immunosuppressive drugs (ID) alongside Rituximab, followed by maintenance for partial responders (PR) or immunochemotherapy for progression disease (PD). The management of refractory/relapsed (R/R) remains uncertain. The role of CD19 CAR-T cells is not established, though case reports and a series of 22 patients have been published.</p><p><b>Methods:</b> We conducted a retrospective analysis of the multicenter French DESCAR-T registry (NCT04328298) to identify patients treated by CD19 CAR-T cells for SOT-related PTLD. The study period spanned from July 2019 to September 2024. Survival analyses were performed using Kaplan-Meier models.</p><p><b>Results:</b> We identified 12 patients (5 males) treated by CD19 CAR-T cells. Prior SOTs included kidneys (<i>n =</i> 10), liver (<i>n =</i> 1) and lungs (<i>n =</i> 1). In all but one patient, lymphoproliferation occurred more than one year after SOT. All PTLD were classified as diffuse large B cell lymphoma (EBV-associated in 10/11, 1 not available (NA)), except one diagnosed as transformed marginal zone lymphoma. CAR-T cells were administered as second line treatment in 3 patients, and beyond second line in 9 patients. The median age at infusion was 41 years (IQR: 22–62). At diagnosis, performance status was 0-1 in 11/12, Ann-Arbor stage was III-IV in 8/12 and aaIPI score was 1-2 in 11/12 patients. The median lymphocyte rate at apheresis was 0.6G/L (IQR:0-3.4). CAR-T products used included axicabtagene ciloleucel (<i>n =</i> 9) and tisagenlecleucel (<i>n =</i> 3). Ten patients received cyclophosphamide-fludarabine as conditioning regimen (2 NA). ID was modified in all patients at diagnosis then before apheresis. At CAR-T infusion, patients were receiving corticosteroids alone (<i>n</i> = 8), m-TOR inhibitor (<i>n</i> = 1), corticosteroids and calcineurin inhibitor (<i>n =</i> 1), or no ID (<i>n =</i> 2). Cytokine-release-syndrome occurred in all patients with grade 3–4 in 2 cases. Immune-effector-cell associated neurotoxicity (ICANS) was observed in 7 patients with grade 3–4 in 2 cases. Hypogammaglobulinemia (< 5 g/L) was reported in 70% of patients (7/10) without need of immunoglobulins replacement. The best ORR was 82%, including 64% complete response, 18% PR and 18% PD. With a median follow-up of 12.9 months (mo) (95% CI: 4.5-(-)), median progression-free-survival and overall survival were both 16.6 mo (95% CI: 1.1-(-) and 2-(-), respectively) (Figure). Six patients died among which three due to PD and 2 from high grade ICANS (one acute, one late) (1 NA). Among the six surviving patients, one experienced kidney rejection requiring a return to dialysis.</p><p><b>Conclusion:</b> This is the second reported series of patients with R/R SOT-related PTLD treated with CD19 CAR-T cells. Our findings suggest that ","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70094_381","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IMAGING PITFALLS IN PEDIATRIC, ADOLESCENT, AND YOUNG ADULT HODGKIN LYMPHOMA: A SEARCH FOR CAYAHL INITIATIVE TO BRIDGE MULTIDISCIPLINARY PATIENT CARE","authors":"N. Dakhallah,&nbsp;J. Steglich,&nbsp;A. L. Alazraki,&nbsp;S. M. Castellino,&nbsp;K. Dieckmann,&nbsp;J. E. Flerlage,&nbsp;C. Gowdy,&nbsp;M. B. Heneghan,&nbsp;K. M. Kelly,&nbsp;H. A. Lai,&nbsp;C. Mauz-Körholz,&nbsp;K. M. McCarten,&nbsp;S. Milgrom,&nbsp;R. Pabari,&nbsp;M. Palese,&nbsp;S. D. Voss,&nbsp;L. Kurch,&nbsp;D. Stoevesandt,&nbsp;J. Seelisch","doi":"10.1002/hon.70094_374","DOIUrl":"https://doi.org/10.1002/hon.70094_374","url":null,"abstract":"<p>N. Dakhallah and J. Steglich equally contributing author.</p><p><b>Introduction:</b> Hodgkin lymphoma (HL) is a highly curable malignancy in children, adolescents, and young adults (CAYA), and current treatment strategies aim to minimize adverse late effects. Many patients are enrolled in clinical trials that include centralized review for both initial and interim staging. While academic guidelines provide a structured framework, real-world clinical scenarios sometimes present imaging pitfalls that require nuanced judgment.</p><p><b>Methods</b>: The Staging, Evaluation and Response Criteria (SEARCH) for CAYAHL initiative was established in 2011 to harmonize staging and response criteria in HL in CAYA. However, applying these published criteria can present challenges in situations where imaging pitfalls are encountered. This SEARCH for CAYAHL project is a transatlantic collaboration among experts in diagnostic radiology, nuclear medicine radiology, radiation oncology and pediatric oncology. A working group first identified the most frequent and relevant imaging pitfalls in HL. Through literature review, imaging and clinical experience, and the use of specific real-word cases, this effort defines and describes imaging pitfalls in HL in CAYA.</p><p><b>Results</b>: Morphologic and metabolic imaging pitfalls in HL refer to the misinterpretation of findings that can occur during staging, disease evaluation, or post-treatment surveillance. These radiological findings are not indicative of disease but are rather manifestations of other causes that are specific to each tissue or organ. In this work, we explore pitfalls resulting from suboptimal imaging conditions, concurrent inflammatory, infectious, or other causes. We discuss organ specific pitfalls involving the lymph nodes, lungs, bone, bone marrow, spleen, liver and Waldeyer’s ring and present important considerations on imaging following the completion of therapy.</p><p><b>Conclusions</b>: This collaborative effort aims to disseminate insights gained from decades of centralized review experience in North American and European trials to optimize patient care by integrating imaging and clinical expertise. Although not intended as a comprehensive staging guide, it highlights recurrent imaging pitfalls that may lead to diagnostic uncertainty. By encouraging interdisciplinary exchange, this work seeks to complement existing literature and serve as a troubleshooting guide for situations where clinical realities diverge from academic paradigms, ultimately paving the way for improved patient outcomes.</p><p><b>Keywords:</b> Hodgkin lymphoma (pediatric, adolescent, and young adult)</p><p><b>Potential sources of conflict of interest:</b></p><p><b>C. Mauz-Körholz</b></p><p><b>Employment or leadership position:</b> Institutional research grant Merck</p><p><b>Consultant or advisory role:</b> Merck advisory board</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70094_374","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MULTICENTER REAL-WORLD OUTCOMES OF FRONTLINE POLA-R-CHP IN TREATMENT NAÏVE DLBCL","authors":"S. K. Thiruvengadam,&nbsp;L. Chen,&nbsp;S. Buller,&nbsp;V. Iyengar,&nbsp;G. Pelaez,&nbsp;V. Pizzuti,&nbsp;A. Major,&nbsp;Y. Youssef,&nbsp;Y. Sawalha,&nbsp;D. Wallace,&nbsp;M. Masterson,&nbsp;N. Birrer,&nbsp;A. Bock,&nbsp;A. Nedved,&nbsp;Y. Wang,&nbsp;T. Lucido,&nbsp;J. Rhodes,&nbsp;J. Crombie,&nbsp;D. Montana,&nbsp;M. Stanchina,&nbsp;J. P. Alderuccio,&nbsp;A. Gibson,&nbsp;P. A. Riedell,&nbsp;T. Jain,&nbsp;B. Heyman,&nbsp;H. Rasmussen,&nbsp;C. Ujjani,&nbsp;P. Gould,&nbsp;H. Cherng,&nbsp;A. Bahnasy,&nbsp;T. Hilal,&nbsp;B. Parker,&nbsp;M. A. Moustafa,&nbsp;S. Pak,&nbsp;M. Okwali,&nbsp;J. Chicola,&nbsp;J. M. Manzano,&nbsp;C. Goth,&nbsp;D. Russler-Germain,&nbsp;P. Torka,&nbsp;A. F. Herrera","doi":"10.1002/hon.70094_289","DOIUrl":"https://doi.org/10.1002/hon.70094_289","url":null,"abstract":"&lt;p&gt;&lt;b&gt;Introduction:&lt;/b&gt; Incorporation of polatuzumab vedotin into initial therapy of diffuse large B-cell lymphoma (DLBCL) became a standard of care (SOC) based on the POLARIX trial, which demonstrated improvement in progression free survival (PFS) with pola-R-CHP compared to R-CHOP. In this study we evaluate the safety and efficacy of SOC frontline pola-R-CHP for treatment naïve DLBCL.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; We performed a multicenter retrospective study including patients (pts) from 17 US centers. Pts with treatment naïve DLBCL who received pola-R-CHP as frontline therapy outside of the setting of a clinical trial were eligible. The primary objective was to evaluate the PFS of SOC pola-R-CHP in frontline DLBCL. Secondary objectives included evaluating the safety of the regimen as well as secondary measures of efficacy such as overall response rate (ORR), complete response rate (CRR), overall survival (OS), and time to next treatment (TTNT).&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; A total of 535 pts treated with pola-R-CHP between August 2021 to September 2024 were included. At least one cycle of alternate treatment was given in 28% pts before switching to pola-R-CHP (78% of these pts received R-CHOP). The median age was 67 years (range 22–90), 41% were female, 17% had ECOG ≥ 2, 89% had advanced stage, 45% had &gt; 1 extranodal site, 63% had elevated LDH, 63% had an IPI of 3–5, 33% had bulky disease (≥ 7.5 cm), 3.3% had central nervous system involvement, 29% were double expressor, 3.9% were double/triple hit, 34% had germinal center B-cell subtype (GCB) and 59% had non-GCB subtype by Hans.&lt;/p&gt;&lt;p&gt;ORR was 92% with a CRR of 80% in all pts; ORR was 93% versus 92% (CRR 77% vs. 81%) for GCB versus non-GCB. At a median follow up of 11 months (range 0.5–32), 1-year PFS was 81% (95% CI: 77%–84%) among all pts, 78% for GCB versus 82% for non-GCB; 1-year OS was 91% (95% CI: 87%–93%) among all pts and 91% for both cell of origin (COO) subgroups. Subsequent treatment was given in 16% pts with median TTNT 5.8 months (range 0.8–18).&lt;/p&gt;&lt;p&gt;With respect to safety, 37% developed any grade neuropathy with 1.1% grade ≥ 3, 20% had grade ≥ 3 infection, 3.4% had cardiomyopathy, 31% had grade ≥ 3 neutropenia, 15% had grade ≥ 3 febrile neutropenia, and 15% had grade ≥ 3 thrombocytopenia. 31% were hospitalized and 6.0% had ICU admission for treatment-related adverse events. Treatment was discontinued in 13% due to toxicity (4.5%), progression (3.6%), or other reasons (4.7%). Seven deaths (1.3%) were deemed to be related to pola-R-CHP.&lt;/p&gt;&lt;p&gt;In univariate Cox models, &gt; 1 extranodal sites, bulky disease, CNS involvement, and double/triple hit were associated with inferior PFS (&lt;i&gt;p&lt;/i&gt; &lt; 0.05) and ECOG ≥ 2, elevated LDH, and IPI 3–5 were associated with inferior OS and PFS (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). COO was not significantly associated with PFS or OS.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusion:&lt;/b&gt; The results of our study suggest that SOC pola-R-CHP is safe and effective for treatment naïve DLBCL, with outcomes","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70094_289","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"OUTCOMES IN AN INTERNATIONAL MULTICENTRE STUDY OF 600 PATIENTS WITH CNS RELAPSE OF LARGE B CELL LYMPHOMA: COMPARTMENT OF RELAPSE IS PROGNOSTIC","authors":"D. Baggio,&nbsp;S. Han,&nbsp;P. Ghione,&nbsp;I. Okcu,&nbsp;J. Okosun,&nbsp;M. Kamdar,&nbsp;A. Kuhnl,&nbsp;N. Grover,&nbsp;H. Cherng,&nbsp;A. Olszewski,&nbsp;P. Ramakrishnan Geethakumari,&nbsp;J. Smith,&nbsp;A. Prica,&nbsp;J. Khwaja,&nbsp;W. Osborne,&nbsp;J. Koff,&nbsp;D. El-Sharkawi,&nbsp;N. Wagner-Johnston,&nbsp;J. Munoz,&nbsp;A. Desai,&nbsp;N. Epperla,&nbsp;F. Baidoun,&nbsp;T. Moyo,&nbsp;M. Narkhede,&nbsp;A. Barrett,&nbsp;K. Linton,&nbsp;D. Wallace,&nbsp;N. Elmusharaf,&nbsp;J. Sandoval-Sus,&nbsp;A. Danilov,&nbsp;J. Rhodes,&nbsp;A. Santarsieri,&nbsp;F. Karim,&nbsp;J. Calabrese De Feo,&nbsp;R. Tavarozzi,&nbsp;I. Nizamuddin,&nbsp;N. Dong,&nbsp;A. Saha,&nbsp;W. Hann,&nbsp;Y. Wang,&nbsp;R. Treitman,&nbsp;A. Maraj,&nbsp;S. Tolu,&nbsp;T. Ollila,&nbsp;C. Abeyakoon,&nbsp;V. Calvert,&nbsp;A. Ayers,&nbsp;A. Hilali,&nbsp;I. Trutzer,&nbsp;S. Monick,&nbsp;J. Sharp,&nbsp;H. Tun,&nbsp;N. Ghosh,&nbsp;G. P. Collins,&nbsp;V. Deshani,&nbsp;J. Can,&nbsp;A. Kallam,&nbsp;B. Kahl,&nbsp;J. Chavez,&nbsp;K. Cwynarski,&nbsp;J. P. Alderuccio","doi":"10.1002/hon.70094_339","DOIUrl":"https://doi.org/10.1002/hon.70094_339","url":null,"abstract":"&lt;p&gt;D. Baggio, S. Han, K. Cwynarski, and J. P. Alderuccio equally contributing author.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Background&lt;/b&gt;: Secondary central nervous system lymphoma (SCNSL) is a rare disease defined by involvement of the CNS concurrent to or following a diagnosis of systemic large B-cell lymphoma (LBCL). This international multicentre cohort study aimed to determine survival outcomes in patients (pts) with isolated CNS relapse (RI-SCNSL) and synchronous systemic/CNS relapse (RS-SCNSL).&lt;/p&gt;&lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; Pts ≥ 18 years treated 2001–2023 at 35 US, UK and Canadian centres were included. CNS involvement was categorised as: brain parenchyma, spine, leptomeninges, vitreoretinal, or &gt; 1 compartment. The primary outcomes were time-to-CNS event from LBCL diagnosis, and progression-free and overall survival (PFS and OS) from time of CNS involvement.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Six hundred pts were included: 393 RI-SCNSL and 207 RS-SCNSL. Prior systemic LBCL treatment was RCHOP (450; 75%) or REPOCH (82; 14%) in the majority; median age at LBCL diagnosis was 62 (range 53–69); and CNS IPI was 4–6 in 139 (23%). Intrathecal and systemic methotrexate prophylaxis was delivered in 40 (10%) and 44 (11%) RI-SCNSL, and 29 (14%) and 33 (16%) RS-SCNSL respectively. Of RI-SCNSL, involvement of parenchyma (&lt;i&gt;n&lt;/i&gt; = 257; 65%), leptomeninges (62; 16%), spine (14; 3.5%), vitreoretinal (11; 2.8%) and &gt; 1 compartment (49; 2.5%) were observed. Of RS-SCNSL, these represented 77 (37%), 77 (37%), 15 (7.2%), 2 (1.0%) and 36 (17%), respectively.&lt;/p&gt;&lt;p&gt;Median time-to-CNS event was 10.3 months (range 6.6–25.6) for RI-SCNSL and 8 months (5.5–16.5) for RS-SCNSL (&lt;i&gt;p&lt;/i&gt; = 0.0001). Median PFS and OS were superior for RI-SCNSL (14.7 and 22.6 months) compared to RS-SCNSL (6.8 and 8.2 months, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001). Median time-to-CNS event was longer in both RI-SCNSL (&lt;i&gt;p&lt;/i&gt; &lt; 0.0001) and RS-SCNSL (&lt;i&gt;p&lt;/i&gt; = 0.019) for parenchymal (13.1 and 10.9 months for RI and RS-SCNSL) and vitreoretinal disease (10.8 and 27.1 months for RI and RS-SCNSL) than leptomeningeal disease (6.9 months in both groups). In RI-SCNSL, CNS compartment was prognostic of PFS (&lt;i&gt;p&lt;/i&gt; = 0.023), longest for vitreoretinal (median 117.4 months) and shortest for leptomeningeal disease (median 7.6 months). Outcomes were poor irrespective of CNS compartment in RS-SCNSL.&lt;/p&gt;&lt;p&gt;Comparing 139 patients with leptomeningeal to 257 with parenchymal involvement, leptomeningeal disease was enriched for &lt;i&gt;MYC/BCL2&lt;/i&gt; double-hit status (20% versus 6.3% of parenchymal, &lt;i&gt;p&lt;/i&gt; = 0.0002), ≥ 3 extranodal sites at LBCL diagnosis (17% versus 9.3%, &lt;i&gt;p&lt;/i&gt; = 0.013), and bone marrow involvement (37% versus 17%, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001). Conversely, isolated parenchymal involvement was enriched for a history of testicular LBCL (12% versus 3.6%, &lt;i&gt;p&lt;/i&gt; = 0.017).&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusion:&lt;/b&gt; Compartment of relapse holds prognostic significance in SCNSL. PFS and OS are significantly better for RI-SCNSL compared to RS-SCNSL. Isolated vitreoretina","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70094_339","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"THE ROLE OF STEM CELL TRANSPLANTATION IN PATIENTS WITH R/R CLASSICAL HODGKIN LYMPHOMA TREATED WITH CHECKPOINT INHIBITORS: ITALIAN MULTICENTER EXPERIENCE","authors":"E. Lucchini,&nbsp;R. Sciarra,&nbsp;V. Tomarchio,&nbsp;S. Pelliccia,&nbsp;M. Marangon,&nbsp;E. Maiolo,&nbsp;M. Novo,&nbsp;L. Schiattone,&nbsp;M. Farina,&nbsp;G. Scapinello,&nbsp;F. M. Quaglia,&nbsp;J. Olivieri,&nbsp;L. Pagliaro,&nbsp;P. Angelillo,&nbsp;L. Mannelli,&nbsp;C. Ghiggi,&nbsp;F. Zaja","doi":"10.1002/hon.70094_364","DOIUrl":"https://doi.org/10.1002/hon.70094_364","url":null,"abstract":"&lt;p&gt;There is no agreement on the role and positioning of stem cell transplantation (SCT) in patients (pts) with relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL) who undertake treatment with checkpoint inhibitors (CPI). The aim of this study is to evaluate the real-world outcomes of R/R cHL pts treated with CPI, particularly the use of consolidation with autologous (autoSCT) and allogeneic SCT (alloSCT). Observational, retrospective, multicenter study which enrolled consecutive pts with R/R cHL aged 18–70 years, treated with CPI monotherapy in Italy from January 2016 to June 2023. Primary objective was the proportion of pts who received consolidation with alloSCT.&lt;/p&gt;&lt;p&gt;We enrolled 126 pts from 15 Italian centers. Median age at CPI start was 36 years (18–70), 54% males, 95% received first-line ABVD, 51% previously received autoSCT and 98% brentuximab vedotin. Eighty-six pts (68%) were treated with pembrolizumab, 40 (32%) with nivolumab. Overall response rate to CPI was 81%, with 49% complete responses (CRs). 107 pts (85%) were considered fit for alloSCT, of those 62 (58%) were planned to receive alloSCT. Ultimately, 41 pts (32%) received alloSCT, 36 (29%) autoSCT and 49 (39%) received no consolidation. Reasons for not performing alloSCT in candidates were progressive disease (PD) (&lt;i&gt;n&lt;/i&gt; = 9), donor unavailability (&lt;i&gt;n&lt;/i&gt; = 4), patient’s refusal or comorbidities (&lt;i&gt;n&lt;/i&gt; = 4), others (&lt;i&gt;n&lt;/i&gt; = 4). Twenty-nine out of 41 allo-transplanted pts (70%) had already received an autoSCT before CPI. Reasons for not administering a consolidation after CPI were age/comorbidity (&lt;i&gt;n&lt;/i&gt; = 19), center’s choice (&lt;i&gt;n&lt;/i&gt; = 9), alloSCT refusal or donor unavailability (&lt;i&gt;n&lt;/i&gt; = 9), PD (&lt;i&gt;n&lt;/i&gt; = 7), other (&lt;i&gt;n&lt;/i&gt; = 5).&lt;/p&gt;&lt;p&gt;In pts who consolidated with alloSCT or autoSCT, median PFS and OS were not reached at a median follow-up of 27 (range 7–90) and 47.5 months (range 4–99) from CPI treatment, respectively. 48-months PFS probability were 80.6% and 81% for alloSCT and autoSCT recipients. Transplant-related mortality after alloSCT was 14.6%. In non-consolidated pts, at a median follow-up of 21 months, median PFS was 27 months. Seventeen pts (35%) were still receiving CPI at last follow-up; the main reason for interruption was PD, in 18/32 pts (56%). In pts who received SCT consolidation there was no difference in terms of PFS according to the obtainment of a CR with CPI (&lt;i&gt;p&lt;/i&gt; = 0.93 for alloSCT and &lt;i&gt;p&lt;/i&gt; = 0.6 for autoSCT). Instead, pts who didn’t consolidate had a significantly poorer outcome if they didn’t obtain a CR with CPI (median PFS not reached versus 11 months; &lt;i&gt;p&lt;/i&gt; &lt; 0.001)—Figure 1.&lt;/p&gt;&lt;p&gt;Outcomes after autoSCT and alloSCT consolidation are excellent, regardless of the response achieved with CPI; alloSCT was burdened by higher toxicity. Pts who achieved a CR with CPI showed good outcomes even without consolidation, however autoSCT should be considered if not performed before. Pts who do not achieve/loss the CR and hav","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70094_364","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ANBALCABTAGENE AUTOLEUCEL (PD-1 AND TIGIT KNOCKDOWN CD19 CAR-T) FOR RELAPSED/REFRACTORY LARGE B-CELL LYMPHOMA (CRC01-01)","authors":"W. S. Kim,&nbsp;S. J. Kim,&nbsp;D. H. Yoon,&nbsp;H. W. Cho,&nbsp;S. E. Yoon,&nbsp;D. H. Yang,&nbsp;H. Shin,&nbsp;H. S. Eom,&nbsp;E. Y. Lee,&nbsp;J. M. Byun,&nbsp;Y. I. Koh,&nbsp;D. Y. Shin,&nbsp;J. Hong,&nbsp;H. W. Lee,&nbsp;J. H. Jung,&nbsp;S. S. Yoon,&nbsp;G. Y. Song,&nbsp;D. Y. Kim","doi":"10.1002/hon.70094_319","DOIUrl":"https://doi.org/10.1002/hon.70094_319","url":null,"abstract":"&lt;p&gt;&lt;b&gt;Introduction:&lt;/b&gt; Anbal-cel is CD19 CAR-T with PD-1, TIGIT knockdown to reduce the negative impact on response. This approach is expected to exert a stronger and more sustained effect on tumor cells.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; In this multicenter, phase 2 trial, we enrolled adult patients with relapsed or refractory large B-cell lymphomas including DLBCL-NOS, HGBL, PMBCL, FL3B. Lymphodepletion was performed with cyclophosphamide 500 mg/m&lt;sup&gt;2&lt;/sup&gt; and fludarabine 30 mg/m&lt;sup&gt;2&lt;/sup&gt;, administered for three days (-5, -4, -3 days). The median dose was 2.2 ×10&lt;sup&gt;6&lt;/sup&gt;cells/kg (range, 0.2–2.61 (×10&lt;sup&gt;6&lt;/sup&gt;cells/kg)). The primary endpoint is ORR by independent review committee. The secondary endpoints are PFS, OS and safety.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Between January 2022 and September 2023, 91 patients underwent leukapheresis to manufacture and 79 patients received anbal-cel. Most patients were DLBCL, NOS (94.9%) and 65 years or older accounted for 53.2%. The patients who had received up to second-line chemotherapy was 70.9%. The IPI score was distributed as follows: low in 31.6%, low-intermediate in 25.3%, high-intermediate in 34.2%, high in 8.9%. The median SPD was 1858 mm&lt;sup&gt;2&lt;/sup&gt; (range, 150–13,724), and the median TMTV was 63.3 ml (range, 0–3603). 26.3% of patients had GCB phenotype, and 61.8% were classified as double expressors.&lt;/p&gt;&lt;p&gt;73 patients included in an efficacy analysis set. The ORR was 75.3% and CR rate was 67.1%. The median f/u time was 8.5 months (range, 0.2–22.6). The median PFS was 6.0 months (95% CI: 4.3–16.5 months), with 12-month and 18-month PFS rates of 41.1% and 35.2%, respectively. The median OS was not reached, and the 12-month and 18-month OS rates were 66.6% and 57.3%, respectively. Regarding CAR-T cell expansion, the responder group exhibited a significantly higher peak expansion (median C&lt;sub&gt;max&lt;/sub&gt;: 22,281 copies/µg) compared to the non-responder group (median C&lt;sub&gt;max&lt;/sub&gt;: 9781 copies/µg).&lt;/p&gt;&lt;p&gt;We categorized patients into long-term responders (LR) and non-long-term responders (non-LR) based on whether they maintained CR at 6 months. FACS analysis showed that PD-1 and TIGIT expression on anbal-cel was significantly lower in the LR group compared to the non-LR group, with this difference persisting at days 14. Additionally, CAR-T cells in the LR group displayed a less activated memory phenotype, characterized by lower expression of CD39 and Tim-3 and higher expression of CD127, compared to those in the non-LR group. Consistent with this, the non-LR group exhibited an increased frequency of terminally differentiated and functionally senescent CAR-T cells, marked by the expression of CD57, CD38, and HLA-DR.&lt;/p&gt;&lt;p&gt;CRS and neurologic events occurred in 57.0% and 13.9%, respectively. Grade 3 CRS occurred in 8.9% with no cases of grade 4. Neurologic events of grade 3 or higher were reported in 3.8%. The rate of serious infections was 25%, prolonged cytopenia was reported in 44% of patients.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclus","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70094_319","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"OUTCOMES OF PATIENTS WITH PRIMARY REFRACTORY AND EARLY RELAPSING LARGE B CELL LYMPHOMA ARE INFERIOR IN THE CD19 CAR T CELL THERAPY ERA","authors":"I. Y. Gong,&nbsp;M. Marinoni,&nbsp;M. Azab,&nbsp;T. Aoki,&nbsp;S. Bhella,&nbsp;C. Chen,&nbsp;R. Kridel,&nbsp;V. Kukreti,&nbsp;A. Prica,&nbsp;A. Vijenthira,&nbsp;C. Yang,&nbsp;D. Hodgson,&nbsp;N. Malik,&nbsp;D. Rodin,&nbsp;W. Wells,&nbsp;M. Crump,&nbsp;J. Kuruvilla","doi":"10.1002/hon.70094_311","DOIUrl":"https://doi.org/10.1002/hon.70094_311","url":null,"abstract":"&lt;p&gt;&lt;b&gt;Introduction:&lt;/b&gt; Although early relapse in relapsed/refractory (R/R) large B cell lymphoma (LBCL) is associated with worse outcomes, the definition of primary refractory disease (PRD) has varied. This study aimed to evaluate the association of time to relapse (TTR) on the trajectory of second line (2L) treatments and outcomes.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; This retrospective study included pts aged ≥ 18 with R/R LBCL at Princess Margaret Cancer Centre (2017–2024, follow-up 01/25). TTR was categorized as PRD (progression during or at end of 1L treatment or &lt; 3 mos), early relapse within 3–12, 12–24, or ≥ 24 mos of 1L rituximab-based therapy. Univariate and multivariable Cox regression analyses assessed the association between TTR and overall survival (OS) and progression-free survival (PFS) from first (OS1, PFS1) and second progression (OS2). Covariates included age, diagnosis, rIPI, and LDH.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Of 367 pts (median age 61, 63% male) included, pts with PRD were more likely to have HGBL and GCB subtype. There were no significant differences in characteristics between relapse groups at first progression (Table 1). For 2L treatment, 86% received platinum-based salvage chemotherapy (SC), and 48% underwent ASCT. Response rates were significantly higher in TTR ≥ 24 mos (81%) compared to PRD (50%), 3–12 mos (60%), and 12–24 mos (68%) (&lt;i&gt;p&lt;/i&gt; &lt; 0.001). At median follow-up of 41 mos, 245 (67%) of pts progressed, and 154 (42%) died. The 5-y OS1 was 45%; median OS1 for PRD and early relapse (3–12 mos) was 23 and 24 months, respectively, compared to not reached for relapse ≥ 24 mos (12–24 mos 56 mos). Cox analysis showed PRD and early relapse ≤ 12 mos were associated with inferior OS1 and PFS1 (OS1: PRD aHR 3.8: 95% CI: 2.1–7.2, &lt;i&gt;p&lt;/i&gt; &lt; 0.001; 3–12 mos aHR 3.3: 1.7–6.5, &lt;i&gt;p&lt;/i&gt; &lt; 0.001), while 12–24 mos was not (aHR 1.7: 0.7–4.1, &lt;i&gt;p&lt;/i&gt; = 0.25) (Figure 1). Sensitivity analysis in de novo LBCL pts did not change these findings. Of the 245 patients who progressed after 2L, 120 (49%) had PRD after 1L. PRD and early relapse were associated with refractoriness to 2L treatment (92% and 67%, vs. 50%; &lt;i&gt;p&lt;/i&gt; &lt; 0.001). The 5-y OS2 was 34% (median 14 mos). Cox analysis showed PRD and early relapse were associated with worse OS2 compared to ≥ 24 mos (PRD aHR 2.3: 1.3–4.3, &lt;i&gt;p&lt;/i&gt; = 0.008; 3–12 mos aHR 2.0: 1.0–3.8, &lt;i&gt;p&lt;/i&gt; = 0.043; 12–24 mos aHR 1.4: 0.6–3.5, &lt;i&gt;p&lt;/i&gt; = 0.43) (Figure 2). For 3L treatment, 215 pts were considered for CAR-T (85% apheresed), and 154 (72%) were CAR-T infused. Multivariable analysis showed the combined cohort of pts with PRD/early relapse &lt; 12 mos was associated with worse OS2 compared to relapse &gt; 12 mos (aHR 2.2: 1.1–4.4, &lt;i&gt;p&lt;/i&gt; = 0.022; mOS2 for early relapse 31 mos vs. NR for late relapse).&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Our study shows that early relapse, particularly pts with PRD, continues to be associated with inferior outcomes even with 3L CAR-T. The association of relapsing timing on 2L","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70094_311","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CIRCULATING TUMOR DNA SEQUENCING REVEALS RAPID RESPONSE KINETICS TO ANTI-PD1 BASED FIRST-LINE TREATMENT OF HODGKIN LYMPHOMA: MOLECULAR INSIGHTS FROM THE GHSG NIVAHL TRIAL","authors":"J. Heger,&nbsp;J. Mattlener,&nbsp;P. Herhaus,&nbsp;J. Meissner,&nbsp;K. Trautmann-Grill,&nbsp;C. Voltin,&nbsp;J. Schneider,&nbsp;J. K. Schleifenbaum,&nbsp;S. Heidenreich,&nbsp;C. Kobe,&nbsp;H. Kaul,&nbsp;W. Klapper,&nbsp;B. von Tresckow,&nbsp;P. J. Bröckelmann,&nbsp;S. Borchmann","doi":"10.1002/hon.70093_43","DOIUrl":"https://doi.org/10.1002/hon.70093_43","url":null,"abstract":"&lt;p&gt;P. J. Bröckelmann, S. Borchmann equally contributing authors.&lt;/p&gt;&lt;p&gt;Anti-PD1 immune checkpoint blockade (ICB) has been incorporated into first-line treatment of classic Hodgkin lymphoma (HL) in several clinical trials recently. The GHSG NIVAHL trial demonstrated high response rates to both sequential and concomitant treatment with ICB and chemotherapy (Bröckelmann, &lt;i&gt;JCO&lt;/i&gt;, 2023). However, it remains unclear whether some patients might achieve long-term remission following ICB alone and how to identify them without risking treatment failure. Recently, two studies established a circulating tumor (ct)DNA-based biologic classification of HL including subtypes with an immune escape phenotype that might be particularly sensitive to ICB (Alig, &lt;i&gt;Nature&lt;/i&gt;, 2024; Heger, &lt;i&gt;JCO&lt;/i&gt;, 2024). Despite these advances, the role of biologic HL classifiers and ctDNA-based minimal residual disease (MRD) kinetics during anti-PD1 first-line treatment have not yet been studied.&lt;/p&gt;&lt;p&gt;The multicenter, randomized GHSG phase II NIVAHL trial evaluated an either sequential or concomitant combination of AVD with the anti-PD1 antibody nivolumab (N) in 109 patients with previously untreated, early-stage unfavorable HL. ctDNA sequencing was applied to plasma samples obtained at baseline, one week after treatment initiation and at all three imaging response assessments as previously described (Heger, &lt;i&gt;JCO&lt;/i&gt;, 2024).&lt;/p&gt;&lt;p&gt;Samples were available from 69 (baseline), 23 (after 1xN-AVD or 1xN), 30 (first restaging after 2xN-AVD or 4xN), 24 (end of systemic therapy after cumulatively 4xN-AVD) and 24 (following 30 Gy IS-RT) patients, respectively. Patient characteristics of this subset were representative of the whole study cohort. Strikingly, 6/19 (31.6%) patients achieved MRD negativity following just one infusion of nivolumab. Patients with &lt;i&gt;Inflammatory immune escape HL&lt;/i&gt; or &lt;i&gt;Virally-driven HL&lt;/i&gt; had higher rates of MRD negativity after just one infusion of nivolumab compared with patients with &lt;i&gt;Oncogene-driven HL&lt;/i&gt; (50% versus 23.1%, Figure 1A). At later timepoints, assessment of MRD allowed for the detection of complete molecular response also in patients with remaining metabolic activity by Deauville-score based PET assessment: At the end of systemic therapy, 8/24 (33.3%) patients were PET positive, while MRD indicated complete molecular remission in 24/24 (100%) of patients (Figure 1B). Importantly, with a median follow-up of 41 months, none of the 8 PET positive patients relapsed or died.&lt;/p&gt;&lt;p&gt;Here, we present the first study evaluating the impact of biologic HL classifiers and very early MRD kinetics in HL patients receiving ICB first-line treatment. Our results suggest that molecular risk stratification might allow to select HL patients with exceptional benefit from anti-PD1 ICB alone. In these patients, chemotherapy might be reduced or omitted in future clinical trials. At the end of systemic anti-PD1 based first-line treatment, MRD might allow fo","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70093_43","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LONG-TERM SURVIVAL TRENDS IN ADVANCED-STAGE MANTLE CELL LYMPHOMA: A POOLED ANALYSIS OF SIX RANDOMIZED PHASE III TRIALS FROM 1996 TO 2020","authors":"L. Jiang,&nbsp;M. Ladetto,&nbsp;O. Hermine,&nbsp;J. C. Kluin-Nelemans,&nbsp;M. Unterhalt,&nbsp;M. Dreyling,&nbsp;E. Hoster","doi":"10.1002/hon.70093_133","DOIUrl":"https://doi.org/10.1002/hon.70093_133","url":null,"abstract":"&lt;p&gt;&lt;b&gt;Introduction:&lt;/b&gt; Mantle cell lymphoma (MCL) remains a challenging disease with a poor prognosis, despite advancements in treatment strategies. Since 1996, the German Low-Grade Lymphoma Study Group (GLSG, now German Lymphoma Alliance) and the European MCL Network have conducted six landmark randomized phase III trials—GLSG1996, GLSG2000, European MCL trial 1, MCL Younger, MCL Elderly, and TRIANGLE, which have transformed the standard of care for advanced-stage MCL patients. This study aimed to evaluate survival trends in advanced-stage MCL patients over the past three decades, focusing on the impact of evolving first-line treatments.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; We performed a pooled analysis of six randomized phase III trials including treatment-naïve, advanced-stage MCL patients enrolled between 1996 and 2020. Patients were grouped into four eras (1996–2000, 2000–2004, 2004–2014, 2016–2020) based on trial enrollment periods. Overall survival (OS) was compared across eras using Kaplan-Meier methods and Cox regression models adjusted for MCL International Prognostic Index (MIPI) and treatment regimens. Additionally, we analyzed dynamic survival trends on a continuous time scale using penalized splines.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Among 2541 MCL patients, survival outcomes have improved steadily since 1996. In younger patients (&lt; 60 or ≤ 65 and suitable for high-dose treatment), median OS significantly increased from 4.9 years (5-year OS: 49%) in 1996–2000 to 6.4 years (60%) in 2000–2004, to 13.8 years (73%) in 2004–2014 and was not yet reached (84%) in 2016–2020, with nearly doubled OS in 2004–2014 (vs. 2000–2004: MIPI-adjusted HR [aHR] = 0.56, 95% CI: 0.44–0.72, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001) and 2016–2020 (vs. 2004–2014: aHR = 0.52, 0.41–0.65, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001) (Figure A). In older patients (&gt; 65 or ≥ 60 and ineligible for high-dose treatment)), median OS improved albeit to a less extent from 3.8 years (5-year OS: 40%) in 1996–2000 to 4.3 years (43%) in 2000–2004, and to 4.8 years (49%) in 2004–2014, with improved OS in 2000–2004 (vs. 1996–2000: aHR = 0.70, 0.51–0.96, &lt;i&gt;p&lt;/i&gt; = 0.025) and 2004–2014 (vs. 2000–2004: aHR = 0.80, 0.64–1.02, &lt;i&gt;p&lt;/i&gt; = 0.070) (Figure B). In younger patients, dynamic modeling revealed a sharp decline in mortality risk between 2000 and 2005, followed by sustained improvements (Figure C). In older patients, dynamic modeling showed a constant decrease in risk from 1996 to 2014 (aHR = 0.95, 0.93–0.97, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001) (Figure D). Patients receiving the same treatment regimens had comparable OS across different eras. Adjusting for treatment regimens eliminated most survival trends, underscoring the impact of ASCT, immunochemotherapy, rituximab maintenance, high-dose cytarabine-containing regimen, and ibrutinib on survival improvements.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Survival outcomes in MCL have substantially improved over the past three decades, especially in younger patients, driven largely by advancements in first-line trea","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70093_133","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RITUXIMAB AND EPCORITAMAB AS FIRST-LINE THERAPY FOR PATIENTS WITH HIGH-TUMOR BURDEN FOLLICULAR LYMPHOMA: FIRST RESULTS OF A MULTICENTER PHASE II TRIAL","authors":"R. Merryman,&nbsp;D. S. Wallace,&nbsp;R. Redd,&nbsp;H. A. Walker,&nbsp;R. Tringale,&nbsp;V. Kats,&nbsp;A. Sigmund,&nbsp;I. E. Ahn,&nbsp;A. Bessnow,&nbsp;J. R. Brown,&nbsp;J. L. Crombie,&nbsp;M. S. Davids,&nbsp;D. C. Fisher,&nbsp;C. K. Hahn,&nbsp;E. D. Jacobsen,&nbsp;C. A. Jacobson,&nbsp;A. I. Kim,&nbsp;A. S. LaCasce,&nbsp;O. O. Odejide,&nbsp;E. M. Parry,&nbsp;D. Qualls,&nbsp;C. E. Ryan,&nbsp;A. Sekar,&nbsp;S. Devata,&nbsp;C. Casulo,&nbsp;K. Maddocks,&nbsp;M. Murakami,&nbsp;P. Armand,&nbsp;Y. Sawalha","doi":"10.1002/hon.70094_227","DOIUrl":"https://doi.org/10.1002/hon.70094_227","url":null,"abstract":"&lt;p&gt;R. Merryman and D. S. Wallace equally contributing author.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Introduction:&lt;/b&gt; Patients (pts) with follicular lymphoma (FL) would benefit from chemotherapy-free frontline treatments that provide high response rates, durable remissions, and a favorable safety profile. Epcoritamab (epco) is a CD3xCD20 bispecific antibody (BsAb) approved in multiply relapsed FL where it results in high overall response rates (ORRs). In other settings, debulking therapy before BsAb treatment appears to reduce the risk of cytokine release syndrome (CRS). We hypothesized that treatment with rituximab (R) for debulking before initiation of full dose epco could lower the risk of CRS and deepen responses based on its distinct mechanism of targeting CD20. Here we present the first results of a phase 2 multicenter trial (NCT05783609) of time-limited therapy with R+epco.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; Eligibility criteria include: age ≥ 18, stage II-IV, grade 1–3A FL, requirement for therapy based on modified GELF criteria, and ECOG PS 0–2. In cycle 1 (C1), pts receive 4 weekly doses of R (D −14, −7, 1, 8) and weekly subcutaneous epco on D1 (0.16 mg), D8 (0.8 mg), and D15/D22 (48 mg). Epco is dosed weekly in C2–3 and biweekly in C4–9. After 26 pts enrolled, a 3&lt;sup&gt;rd&lt;/sup&gt; epco step-up dose (D15, 3 mg) was added and inpatient observation for C1D15 was no longer required. Responses are evaluated based on Lugano 2014 criteria after 2, 5, and 9 cycles.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; As of 1/31/2025, 31 of 35 planned pts had enrolled. The median age was 57 (range 28–78). At study entry, 30 pts (97%) had stage III/IV, 8 (26%) bulky disease (≥ 7 cm), 7 (23%) grade 3A FL, and 17 (55%) a FLIPI score of 3–5.&lt;/p&gt;&lt;p&gt;Among 25 response-evaluable pts (6 pts awaiting 1st response assessment), the best ORR and complete metabolic response (CMR) rates were 100% and 92%, respectively. Rapid responses were observed (22 CMRs, 3 partial metabolic responses [PMRs] after 2 cycles of therapy). 1 PMR subsequently converted to a CMR and the other 2 pts have not yet been restaged. With a median follow-up of 6.0 months (m) (range 0–17.6), no pts have relapsed, yielding a 6 m PFS estimate of 100%.&lt;/p&gt;&lt;p&gt;Among 31 safety-evaluable pts, the most common adverse events (AEs) were CRS (48%; G1 39%; G2 6%, no G3+), fatigue (39%), injection site reactions (39%; G1 35%, G2 3%), and infections (39%; G1 6%, G2 23%, G3 10%). G3 infections include bacteremia, COVID-19, and lung infection. In each case, the infection resolved and the pt restarted study treatment. Other common grade 3+ AEs included neutropenia (16%) and lymphocytopenia (6%). 3 pts discontinued treatment due to an AE (persistent G1 rhinovirus, recurrent G1-G2 viral respiratory infections, G3 eosinophilia). All 3 pts were in a CMR at the time of treatment discontinuation.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusion:&lt;/b&gt; R+epco achieves high CMR rates in patients with high tumor burden FL, and debulking therapy with R may lower the risk of grade 2+ CRS. Based on these encouraging resul","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70094_227","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}