Hematological Oncology最新文献

{"title":"PATIENT REPORTED OUTCOMES FROM BRUIN CLL-321: PHASE 3 TRIAL COMPARING PIRTOBRUTINIB TO IDELALISIB/RITUXIMAB OR BENDAMUSTINE/RITUXIMAB IN COVALENT BTKi PRETREATED CLL/SLL","authors":"P. Barr, P. Ghia, D. Rossi, E. Ferrant, F. De la Cruz Vicente, D. Maruyama, V. Banerji, P. Cobb, S. Namburi, R. Greil, A. Loubert, K. Creel, L. M. Hess, N. Payakachat, A. S. Ruppert, D. Wang, P. Abada, C. C. Leow, M. Hill, C. C. Coombs, J. P. Sharman","doi":"10.1002/hon.70094_219","DOIUrl":"https://doi.org/10.1002/hon.70094_219","url":null,"abstract":"<p><b>Introduction:</b> The phase 3, randomized trial BRUIN CLL-321 assessed the safety and efficacy of pirtobrutinib compared to investigators choice (IC) of idelalisib plus rituximab (IdelaR) or bendamustine + rituximab (BR) in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) previously treated with a covalent BTK inhibitor (cBTKi). BRUIN CLL-321 showed significantly improved progression-free survival and longer time to next treatment or death with pirtobrutinib compared to IdealR/BR. Exploratory endpoints of the trial assessed changes from baseline in patient reported outcomes (PROs) through week 25 for patients treated with pirtobrutinib compared to IdelaR/BR.</p><p><b>Methods:</b> Patients with relapsed/refractory CLL/SLL, who received at least one prior cBTKi, were enrolled in BRUIN CLL-321. Endpoints included the evaluation of PROs between groups, as measured by three tools: the EORTC QLQ-C30 physical function (PF) scale, a CLL/SLL-related symptoms scale, and a fatigue scale expanded from the QLQ-C30 fatigue scale. PROs were collected every 4 weeks during study treatment. A positive least square means difference (LSM<sub>d</sub>) PF score reflected PF improvement from baseline in the pirtobrutinib group, while a negative change in symptoms or fatigue LSM<sub>d</sub> reflected improvement in the pirtobrutinib group from baseline compared to IdelaR/BR. Longitudinal analyses used mixed model for repeated measures adjusted for baseline PRO scores. Thresholds for clinically meaningful between-group differences were defined a priori from Cocks et al. (<i>JCO</i> 29 (1):89–96, 2011). The statistical testing of PRO endpoints was not type-1 error controlled and thus descriptive in nature.</p><p><b>Results:</b> A total of 119 patients were randomized to each treatment arm (<i>N</i> = 238). PRO completion rate was 82.1% at baseline and remained above 80% at each subsequent assessment through Week 25. CLL/SLL-related symptoms were clinically meaningfully lower in the pirtobrutinib group versus IdelaR/BR at Week 9 (LSM<sub>d</sub>, −7.3 [standard error (SE), 2.2]), Week 13 (LSM<sub>d</sub>, −6.7 [SE, 2.3]), Week 17 (LSM<sub>d</sub>, −4.6 [SE, 2.3]), and Week 21 (LSM<sub>d</sub>, −7.0 [SE, 2.3]). Patients in the pirtobrutinib group reported lower fatigue scores versus those receiving IdelaR/BR at Week 9 (LSM<sub>d</sub>, −9.0 [SE, 2.9]), Week 13 (LSM<sub>d</sub>, −6.7 [SE, 3.0]), and Week 21 (LSM<sub>d</sub>, −6.9 [SE, 3.1]). Patients in the pirtobrutinib group also reported better PF versus IdelaR/BR at Weeks 13 (LSM<sub>d</sub>, 5.6 [SE, 2.4]) and 21 (LSM<sub>d</sub>, 5.9 [SE, 2.5]).</p><p><b>Conclusions:</b> These analyses suggest a meaningful and clinically relevant improvement in CLL/SLL-related symptoms, physical functioning, and fatigue at most assessments between baseline and Week 25 in the pirtobrutinib group compared to IdelaR/BR. Most PRO assessments met clinically meaningful thresholds, and for those that did n","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70094_219","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300164","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":"LISOCABTAGENE MARALEUCEL IN R/R FL (TRANSCEND FL): IMPACT OF PRIOR LINES OF THERAPY, BENDAMUSTINE EXPOSURE, AND DISEASE PROGRESSION ≤ 24 MONTHS OF INITIAL SYSTEMIC THERAPY","authors":"S. Ahmed, J. L. Reguera Ortega, F. Morschhauser, G. Cartron, A. P. Rapoport, K. Izutsu, H. Ghesquieres, M. L. Palomba, H. Goto, J. Kuruvilla, J. S. Abramson, P. Borchmann, U. Jäger, M. Kamdar, M. Bar, M. Strocchia, M. Raggi, R. Nishii, A. M. García-Sancho","doi":"10.1002/hon.70093_142","DOIUrl":"https://doi.org/10.1002/hon.70093_142","url":null,"abstract":"<p><b>Introduction:</b> In the TRANSCEND FL primary analysis, lisocabtagene maraleucel (liso-cel) showed an ORR of 97%, CR rate of 94%, and favorable safety in patients (pts) with second-line (2L) and third-line or later (3L+) R/R FL. In pts with R/R FL, increasing lines of therapy (LOT), progression of disease ≤ 24 mo from initial immunochemotherapy (POD24), and recent exposure to bendamustine (benda) before CAR T cell therapy may impact pt outcomes. We report results in these pt subgroups with R/R FL from TRANSCEND FL.</p><p><b>Methods:</b> Pts had 3L+ R/R FL or 2L R/R FL after prior treatment (tx) with an anti-CD20 antibody and alkylator. All pts with 2L R/R FL had PD ≤ 24 mo of diagnosis (dx) and tx ≤ 6 mo of FL dx, and/or modified GELF criteria. Post hoc subgroup analyses were performed by number of prior LOTs (4L+, 3L, 2L), POD24 (yes, no), and benda exposure (< 12 mo, 12–24 mo, or > 24 mo before leukapheresis or no benda). Outcomes included ORR, CR rate, duration of response (DOR), and PFS (all by IRC), OS, time to next tx (TTNT), and safety. In the benda subgroups, cellular kinetics were assessed.</p><p><b>Results:</b> Of 130 liso-cel–treated pts, 59 (45%) received liso-cel as 4L+ tx, 48 (37%) as 3L tx, and 23 (18%) as 2L tx; 73 (56%) had POD24 and 56 (43%) did not; 11 (8%) had prior benda < 12 mo, 11 (8%) within 12–24 mo, 49 (38%) > 24 mo, and 59 (45%) had no benda. Median on-study follow-up was 29.7 mo (range, 0.3–39.6). There were no major differences in demographics or baseline characteristics among subgroups.</p><p>ORR was ≥ 96% across subgroups (Table). CR rate was similar across prior LOTs and POD24 subgroups, but lower in pts with prior benda < 12 mo (75%) versus other benda subgroups (≥ 95%), though pt numbers were small in the < 12-mo group (<i>n</i> = 8). Median DOR was not reached (NR) in all but 4L+ and POD24 subgroups (30.9 mo each); median PFS was NR in all but 4L+, POD24, and no benda subgroups (31.8 mo each); and median OS was NR for all subgroups. A trend toward better 24-mo DOR, PFS, and OS was observed with liso-cel in earlier versus later LOTs. Median DOR, median PFS, and 24-mo DOR, PFS, and OS were slightly better in pts without POD24, though still clinically meaningful in pts with POD24. Rates of 24-mo DOR, PFS, and OS were high for all benda subgroups (≥ 72%) except for the 8 pts with prior benda < 12 mo where a trend for worse outcomes was observed (24-mo PFS, 50%). Median TTNT was NR for all subgroups; 24-mo rates were numerically lower for pts with 4L+ versus 3L and versus 2L FL, POD24 versus no POD24, and prior benda < 12 mo versus other benda subgroups. Cellular kinetics were similar among benda subgroups. Safety was consistent across subgroups with low rates of grade ≥ 3 cytokine release syndrome and neurological events, and no new signals observed (Table).</p><p><b>Conclusion:</b> These data support the sustained clinical benefit and manageable safety profile of liso-cel in pts with R","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70093_142","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300260","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":"FOLLICULAR LYMPHOMA EPIDEMIOLOGY AND OUTCOMES IN ENGLAND 2014–2021: PRELIMINARY ANALYSIS FROM THE UNCOVER STUDY GROUP","authors":"K. M. Linton, I. Karpha, Y. Lim, M. Bishton, L. Jeffers, T. Erinfolami, N. Akter, H. Liu, B. Johnston, N. Kalakonda, C. Tudur Smith, M. Clancy, A. Pettitt","doi":"10.1002/hon.70093_96","DOIUrl":"https://doi.org/10.1002/hon.70093_96","url":null,"abstract":"<p><b>Introduction</b>: UNCOVER is a blood cancer health data research programme that utilises the National Cancer Registration Dataset (NCRD). NCRD includes information on all patients diagnosed with all types of cancer in all NHS institutions in England (<i>Int J Epidemiol</i> 2020; 49(1):16–16h).</p><p><b>Methods</b>: NCRD data was obtained for all patients in England diagnosed with any type of blood cancer between Jan 2014 and Dec 2021. Patients with newly diagnosed follicular lymphoma (FL) were identified using ICD-O-3 codes 96953, 96913, 96983, and 96903. Crude and adjusted incidence rate ratios (IRR) were estimated and compared between groups using multivariable Poisson regression, and calendar time trends were assessed. Overall survival (OS), cause-specific and relative survival was assessed using K-M methods and multivariable Cox regression, Fine-Gray and Pohar-Perme models, respectively. All models were adjusted for age, gender, index of multiple deprivation (IMD) quintile and government region, while Cox and Fine-Gray models were also adjusted for ethnicity and Charlson co-morbidity index (CCI).</p><p><b>Results</b>: 17561 patients with FL aged 18–99 were identified (demographics in Table 1). Gender (<i>p</i> < 0.001), age (<i>p</i> < 0.001), ethnicity (<i>p</i> < 0.001), region (<i>p</i> < 0.001) and year of diagnosis (<i>p</i> < 0.001) were independently associated with incidence. The adjusted IRR increased with age and was lower in females (0.90), in mixed-race (0.20), Asian (0.43) and black (0.28) people compared to white people, and in all 8 provincial regions compared to London (IRR for North West 0.81). The adjusted IRR for successive calendar years was generally stable but dipped in the first year of the COVID-19 pandemic [2020 vs. 2014; 0.94 (95% CI: 0.89–1.01)]. Survival data were available until July 2023 [median follow-up 4.4 years (IQR: 2.4–6.6)]. 4709 (26.8%) patients died, with 5-year OS 74% (95% CI: 74%–75%) and relative survival 85% (84%–86%). Gender (<i>p</i> < 0.001), age (<i>p</i> < 0.001), ethnicity (<i>p</i> = 0.044), CCI (<i>p</i> < 0.001), IMD (<i>p</i> < 0.001) and year of diagnosis (<i>p</i> = 0.008) were independently associated with OS. The adjusted hazard ratio (HR) increased with age [15.4 (95% CI: 11.6–20.6) for 75–99 vs. 18–44], deprivation [1.47 (1.33–1.61) for IMD1 vs. IMD5] and comorbidity [2.35 (2.09–2.64) for CCI ≥ 4 vs. 0] but was lower in females [0.78 (0.73–0.82)], in black versus white people [0.60 (0.38–0.93)], and in patients diagnosed in 2015 versus 2014 [0.86 (0.78–0.96)].</p><p><b>Conclusion</b>: Our findings shed new light on FL epidemiology and outcomes in England during the period 2014–2021. Even when other variables such as age and comorbidity were taken into account, reported incidence was lower and survival shorter in people living in more deprived areas, identifying a group with significant unmet needs. A significant proportion of patients died of unrelated","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70093_96","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300262","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":"A MULTI-CENTER, PROSPECTIVE STUDY OF THE EFFICACY AND SAFETY OF PD-1 ANTIBODY SINTILIMAB IN COMBINATION WITH PEGASPARGASE AND ANLOTINIB IN STAGE IV NKTCL PATIENTS","authors":"R. Tao, C. Liu, W. Zhang, J. Wan, Y. Ma, Y. Zhu, L. Ma, S. Tian, H. Ding","doi":"10.1002/hon.70094_400","DOIUrl":"https://doi.org/10.1002/hon.70094_400","url":null,"abstract":"<p><b>Introduction:</b> Stage IV Natural killer/T-cell lymphoma (NKTCL) has a poor prognosis. Asparaginase is the backbone drug for the treatment of NKTCL. Anti-PD-1 antibody is effective for relapsed/refractory NKTCL. Our previous study found that angiogenesis inhibitor anlotinib was active in relapsed/refractory NKTCL. This study is aimed to investigate the efficacy and safety of Sintilimab, a PD-1 antibody approved in China, in combination with Pegaspargase and anlotinib (LEAP regimen) in the treatment of stage IV NKTCL patients unfit for high-dose induction chemotherapy.</p><p><b>Methods:</b> Eligible patients met the following criteria: (1) Histologically confirmed NKTCL with stage IV classification per Lugano 2014 criteria; (2) Age > 65 years or ≤ 65 years with protocol-defined contraindications to high-dose methotrexate/dexamethasone. The LEAP regimen comprised 3-week cycles (maximum 8 cycles): Sintilimab 200 mg IV day 1; Pegaspargase 2500 IU/m<sup>2</sup> IM day 1; Anlotinib 8 mg PO days 1–14. Complete responders could receive consolidative autologous hematopoietic stem cell transplantation (auto-HSCT) at investigator discretion. The primary endpoint was complete response (CR) rate at 24 weeks by Lugano 2014 criteria. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety analysis using CTCAE v4.0.</p><p><b>Results:</b> Thirty-seven patients were enrolled (median age 64 years; range 32–78; M:F = 22:15) from July 2019 to April 2021. The median treatment duration was 8 cycles (range 2–8), with 72.9% (27/37) achieving CR and an objective response rate of 83.8% (31/37). Disease progression occurred in 16.2% (6/37) during treatment. Following induction therapy, 63.0% (17/27) of CR patients underwent consolidative auto-HSCT versus 37.0% (10/27) who entered observation. With a median follow-up of 48 months (95% CI: 45.2–50.8), the auto-HSCT cohort demonstrated significantly lower relapse rates (17.6% vs. 60.0%, <i>p</i> < 0.05). Survival outcomes revealed 1-/4-year PFS rates of 78.4% (95% CI: 61.4%–88.6%)/56.6% (39.2%–70.7%) and 1-/4-year OS rates of 83.8% (67.4%–92.4%)/75.2% (57.7%–86.3%). All patients experienced treatment-related adverse events (AEs), predominantly grade 1–2 asparaginase-associated toxicities). Grade ≥ 3 AEs included neutropenia (10.8%) and hyperbilirubinemia (10.8%). No AE-related treatment discontinuations occurred.</p><p><b>Conclusions:</b> The LEAP regimen demonstrates robust clinical efficacy (CR rate 72.9%) and favorable tolerability in high-risk stage IV NKTCL patients ineligible for intensive induction chemotherapy. However, the high post-remission relapse rate (60%) in non-consolidated patients underscores the necessity for effective maintenance strategies. Our findings suggest consolidative auto-HSCT significantly improves disease free survival, potentially bridging the gap between immunotherapy and durable remission in this challenging patient population.</p><p><b>Keyw","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70094_400","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300334","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":"RELAPSED/REFRACTORY MATURE B-NHL IN CHILDREN AND ADOLESCENTS","authors":"A. Burke","doi":"10.1002/hon.70093_31","DOIUrl":"https://doi.org/10.1002/hon.70093_31","url":null,"abstract":"<p>Relapsed and refractory (r/r) mature B-NHL in chidlren and adolescents represents an area of unmet cinical need due to the poor prognosis of these patients. Burkitt lymphoma and Diffuse Large B-cell lymphoma are the majority histologies.</p><p>Mulitple new immuno-oncology therapies are available or being investigated in adult r/r mature B-NHL. The rarity of childhod and adolescent disease makes evaluation of all of these impossible and a more strategic approach is required.</p><p>This lecture will explore the challenges of rational new drug development in this rare disease and highlight the current landscape with an emphasis on an international, transatlantic, academic-industry collaborative, fit-for-filing trial -Glo-BNHL (NCT05991388)</p><p><b>Research</b> <b>funding declaration:</b> CRUK, FKC, Multiple industry partners.</p><p><b>Keywords:</b> non-Hodgkin (Pediatric, Adolescent, and Young Adult); immunotherapy; ongoing trials</p><p><b>Potential sources of conflict of interest:</b></p><p><b>A. Burke</b></p><p><b>Other remuneration:</b> Institutional funding from Regeneron, ADCT Therapeutics and BMS for clinical trial</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70093_31","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300333","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-DOSE-ADJUSTED EPOCH VERSUS RITUXIMAB-CHOP IN PRIMARY MEDIASTINAL LARGE B-CELL LYMPHOMA","authors":"T. Vassilakopoulos,&nbsp;Z. Mellios,&nbsp;G. Papageorgiou,&nbsp;A. Piperidou,&nbsp;E. Verigou,&nbsp;C. Chatzidimitriou,&nbsp;C. Kalpadakis,&nbsp;E. Katodritou,&nbsp;H. Giatra,&nbsp;V. Xanthopoulos,&nbsp;G. Gainaru,&nbsp;E. Vrakidou,&nbsp;T. Leonidopoulou,&nbsp;M. Kotsopoulou,&nbsp;M. Palassopoulou,&nbsp;S. Karakatsanis,&nbsp;M. Tsirogianni,&nbsp;E. Hatzimichael,&nbsp;E. Terpos,&nbsp;P. Zikos,&nbsp;C. Poziopoulos,&nbsp;E. Vervessou,&nbsp;M. Arapaki,&nbsp;A. Kopsaftopoulou,&nbsp;A. Liaskas,&nbsp;P. Katsaouni,&nbsp;J. Assimakopoulos,&nbsp;G. Kourti,&nbsp;D. Koutsiafes,&nbsp;M. Siakantaris,&nbsp;G. Karianakis,&nbsp;A. Symeonidis,&nbsp;D. Grentzelias,&nbsp;V. Pappa,&nbsp;P. Tsirigotis,&nbsp;E. Papadaki,&nbsp;E. Plata,&nbsp;M. Bakiri,&nbsp;G. Pangalis,&nbsp;M. Angelopoulou,&nbsp;M. Bouzani","doi":"10.1002/hon.70094_346","DOIUrl":"https://doi.org/10.1002/hon.70094_346","url":null,"abstract":"&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Further to the impressive phase 2 NCI results, retrospective comparisons have shown a modest, non-significant benefit in disease control and a reduced need for consolidative radiotherapy (RT) with R-da-EPOCH versus R-CHOP in PMLBCL. However, the numbers of patients were small-to-moderate (&lt;&lt; 100) and the choice of treatment was at the discretion of the treating physician, inevitably introducing systematic bias.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Aims:&lt;/b&gt; To evaluate the efficacy of R-da-EPOCH versus R-CHOP with an -as much as possible- unbiased selection of control group patients&lt;/p&gt;&lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; R-da-EPOCH was adopted in all consecutive patients with PMLBCL ≤ 65 years (&lt;i&gt;n&lt;/i&gt; = 156) in 18 participating Centers, which were providing R-CHOP as standard of care until that time. The control group of R-CHOP-treated patients was devised from the same Centers’ database, selecting in chronological order (most recent first) an equal number of consecutive patients to those treated with R-da-EPOCH at the same Center, if possible, thus minimizing selection bias. Due to lack of some appropriate controls in a few Centers (&lt; 20 R-CHOP-treated patients less), they were substituted by consecutive patients treated in few of the other centers, which had comparable potential (large or small, public or private centers). R-CHOP-14 was given in 22/156 patients of the control group (14%).&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; The groups of R-da-EPOCH (&lt;i&gt;n&lt;/i&gt; = 156) and R-CHOP-treated patients (&lt;i&gt;n&lt;/i&gt; = 156) were absolutely comparable in terms of patients’ characteristics except for more frequent multiple extranodal involvement in R-CHOP (8.4% vs. 16.0%, &lt;i&gt;p&lt;/i&gt; = 0.042). The 5-year freedom from progression (FFP), event-free survival (EFS) and overall survival (OS) rates for R-da-EPOCH versus R-CHOP were 87.5% versus 75.5% (&lt;i&gt;p&lt;/i&gt; = 0.011), 84.4% versus 75.5% (&lt;i&gt;p&lt;/i&gt; = 0.052 counting 4 t-AML cases after R-da-EPOCH as events) and 94.1% versus 86.9% (&lt;i&gt;p&lt;/i&gt; = 0.039). Among patients potentially eligible for RT (no progressive disease), RT was administered to 10% versus 70% after R-da-EPOCH or R-CHOP. In multivariate analysis, after adjustment for age, gender, multiple extranodal sites and recently published prognostic models (extranodal and LDH &gt; 2x or bulk) the difference between R-da-EPOCH and R-CHOP remained significant regarding FFP, OS and EFS, when the extranodal-LDH model was assessed, but only for FFP when the extranodal-bulk model was taken into account (0.10 &lt; &lt;i&gt;p&lt;/i&gt; &lt; 0.20 for EFS and OS). Only 77 (58%) of 133 patients with currently available data had absolute adherence to R-da-EPOCH protocol, reflecting the real-life situation. These patients had a 5-year FFP of 90.9% and 85.1% (&lt;i&gt;p&lt;/i&gt; = 0.30).&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusion:&lt;/b&gt; Our non-randomized, comparative study is by far the largest one comparing R-da-EPOCH versus R-CHOP and carried the least possible systematic error in the retrospective setting. R-da-EPOCH minimized the need of RT and demonst","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70094_346","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300391","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":"A SHORT (x3) NIVOLUMAB BEFORE BGD CHEMOTHERAPY IMPROVES THE REMISSION RATE IN RELAPSED/REFRACTORY HODGKIN LYMPHOMA: N-BURGUND TRIAL OF THE POLISH LYMPHOMA RESEARCH GROUP","authors":"J. M. Zaucha,&nbsp;E. Paszkiewicz-Kozik,&nbsp;M. Taszner,&nbsp;B. Małkowski,&nbsp;J. Rybka,&nbsp;K. Chromik,&nbsp;A. Kołkowska-Leśniak,&nbsp;E. Subocz,&nbsp;Ł. Targoński,&nbsp;P. Ceklarz,&nbsp;M. Witkowska,&nbsp;K. Domańska-Czyż,&nbsp;A. Giza,&nbsp;R. Swoboda,&nbsp;M. Kobylecka,&nbsp;C. Voltin,&nbsp;J. Romejko-Jarosińska,&nbsp;M. Świerkowska,&nbsp;B. Ostrowska,&nbsp;A. Druzd-Sitek,&nbsp;M. Kurlapski,&nbsp;M. Bednarek,&nbsp;G. Romanowicz,&nbsp;J. Góra-Tybor,&nbsp;J. Hałka,&nbsp;T. Wróbel,&nbsp;S. Giebel,&nbsp;G. Helbig,&nbsp;E. Lech-Marańda","doi":"10.1002/hon.70094_357","DOIUrl":"https://doi.org/10.1002/hon.70094_357","url":null,"abstract":"&lt;p&gt;&lt;b&gt;Introduction&lt;/b&gt;: Achieving complete metabolic remission (CMR) before autologous hematopoietic cell transplantation aHCT in patients with relapsed/refractory (r/r) classical Hodgkin Lymphoma patients (pts) improves their long-term outcomes. BGD (bendamustine, gemcitabine, dexamethasone) in a second line induces CMR in about 70% of r/r HL pts (Paszkiewicz-Kozik et al., &lt;i&gt;Hematological Oncology&lt;/i&gt;, 42, Suppl, p364 2023). The phase 2 N-BURGUND trial (EudraCT 2021-002630-17) evaluates the efficacy and safety of a very short course of Nivolumab (N) (3 cycles) followed by 2 (up to maximum 4) cycles of BGD in r/r HL pts before aHCT &lt;i&gt;having hypothesized&lt;/i&gt; that addition of Nx3 will improve the response to BGD (CMR) by 15%. Here, we present the efficacy and safety results of the enrolled patients.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; Patients aged ≥ 18 years with r/r advanced stage (IIB-IV) HL after first-line treatment were eligible and received N 240 mg IV Q2W for three cycles followed by PET&lt;sub&gt;NIV&lt;/sub&gt; and 2 to max four cycles of BGD (bendamustine 90 mg/m&lt;sup&gt;2&lt;/sup&gt; D1,2; gemcitabine 800 mg/m&lt;sup&gt;2&lt;/sup&gt; on D1,4; dexamethasone 40 mg on D1–4) combined with CD34+ cell mobilization followed by PET&lt;sub&gt;2BGD&lt;/sub&gt;. Patients achieving CMR (Deauville score 1–3 assessed by the Central Reviewer Panel) are subjected to aHCT. The primary endpoint for this analysis is centrally assessed PET&lt;sub&gt;BGD&lt;/sub&gt;-negativity response in patients after two cycles of BGD. The secondary endpoints are PET&lt;sub&gt;NIVO&lt;/sub&gt; response and the results of circulating tumor DNA assessment at the time of PET examinations.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results&lt;/b&gt;: Between December 2022 and November 2024, 86 pts (50% females) with r/r cHL were enrolled from 9 centers affiliated with the PLRG. Median (range) age was 36 years (20–71); 71 (83%) patients received ABVD, 2 (2%) BV+AVD, and 13 (15%) BEACOPPesc in the first line. Forty pts (47%) were primary refractory, including 6 to BEACOPPesc and 2 to BV+AVD; twenty-five (29%) pts had an early relapse (&lt; 12 months), whereas the remaining 21 (24%) had a late relapse. All patients have completed 3 × N and 2 × BGD. Eighty-four PET&lt;sub&gt;NIVO,&lt;/sub&gt; and 78 PET&lt;sub&gt;BGD&lt;/sub&gt; results were available at the time of submission. The PET&lt;sub&gt;NIVO&lt;/sub&gt; negativity rate was 34%. Afterward, the PET&lt;sub&gt;BGD&lt;/sub&gt; negativity rate increased to 86%. In 76 pts with two PET assessments available, BGD improved response in 37 (48%) pts. One patient required two more BGD cycles to achieve CMR. Grade ≥ 3 adverse events (AEs) (26.5% of all AEs) occurred in 13 pts (22% of all pts). Drug-related grade 4 AEs included flare syndrome and anemia caused by pure red cell aplasia, which resolved after 6 months of treatment with steroids, rituximab, and bortezomib. Immune-mediated AEs (3,6% of all AEs) occurred in 5% of patients who received nivolumab. The most common AE was rash (14.5%) (Figure 1). There were no deaths during the study.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusion:&lt;/b&gt; A very short Nivolumab induction fo","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70094_357","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300335","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":"Current Status of Revisions to the Lugano Classification in Lymphoma","authors":"The Organizing Committee of the Lugano Classification Workshop","doi":"10.1002/hon.70103","DOIUrl":"https://doi.org/10.1002/hon.70103","url":null,"abstract":"<p>In the decade since publication of the Lugano Classification (Cheson et al, J Clin Oncol 2014,32:3059–3068; Barrington et al, J Clin Oncol 2014, 32:3048–3058), major advances in lymphoma therapy and assessment, including metabolic tumor volume (MTV) and circulating tumor DNA (ctDNA) prompted a workshop at the International Conference on Malignant Lymphoma-17 entitled “Lugano Classification: Looking Toward the Future”, to determine whether a revision was warranted and what it should look like. This report summarizes the conclusions of that workshop and a subsequent questionnaire of the participants. It was concluded that, whereas, minor modifications could be made now, the current classification should remain the standard until the clinical benefit of MTV and ctDNA are firmly established and practical considerations demonstrated. An ICML sponsored standing committee will monitor progress and ensure that a revision of the Lugano Classification will be proposed when warranted.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70103","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300393","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":"FIXED DURATION TREATMENT OF BENDAMUSTINE-RITUXIMAB AND ACALABRUTINIB IN FRONTLINE WALDENSTROM’S MACROGLOBULINEMIA: DEEP MOLECULAR RESPONSES IN HIGH-RISK PATIENT SUBSETS","authors":"A. Suleman,&nbsp;K. Roos,&nbsp;K. Mangoff,&nbsp;Y. Jiang,&nbsp;G. Klein,&nbsp;D. Villa,&nbsp;D. MacDonald,&nbsp;M. Aljama,&nbsp;M. Shafey,&nbsp;N. Forward,&nbsp;J. Larouche,&nbsp;A. Nikonova,&nbsp;M. Sebag,&nbsp;I. Sandhu,&nbsp;S. Chow,&nbsp;R. McClure,&nbsp;M. Gallucci,&nbsp;H. Simmons,&nbsp;G. Tomlinson,&nbsp;N. L. Berinstein","doi":"10.1002/hon.70093_54","DOIUrl":"https://doi.org/10.1002/hon.70093_54","url":null,"abstract":"&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; An optimal first-line therapy for Waldenstrom’s Macroglobulinemia (WM) has not been defined. We postulated that combining bendamustine and rituximab (BR) with acalabrutinib will result in deep and durable responses, particularly in high-risk patient subsets.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; The BRAWM clinical trial (NCT04624906) combined BR and acalabrutinib in a one-year, fixed duration treatment course of six 28-day cycles of BR and 365 days of concurrent acalabrutinib. This phase II trial took place at 9 clinical sites across Canada. The primary outcome was combined complete response + very good partial response (CR+VGPR) rate, and secondary outcomes included PFS, OS and Measurable Residual Disease (MRD). Outcomes were assessed for all participants, and for high-risk subsets (&lt;i&gt;MYD88&lt;/i&gt;&lt;sup&gt;&lt;i&gt;WT&lt;/i&gt;&lt;/sup&gt;&lt;i&gt;, CXCR4&lt;/i&gt;&lt;sup&gt;&lt;i&gt;MUT&lt;/i&gt;&lt;/sup&gt; and &lt;i&gt;TP53&lt;/i&gt;&lt;sup&gt;&lt;i&gt;MUT&lt;/i&gt;&lt;/sup&gt;). MRD analyses uses bone marrow (BM) and peripheral blood (PB) samples collected at trial specific time points, assessments being performed by Adaptive Biotechnologies (Seattle, USA) using the clonoSEQ assay. Outcomes were compared between high-risk and non-high risk subsets.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; This trial enrolled 63 participants. The median age was 69 years (range 39–85), and 49 (78%) were male, 38% intermediate-risk and 51% high-risk IPSS-WM score. Mutational analysis in 57 participants showed 50 (88%) were &lt;i&gt;MYD88&lt;/i&gt;&lt;sup&gt;&lt;i&gt;MUT&lt;/i&gt;&lt;/sup&gt; and 16 (30%) were &lt;i&gt;CXCR4&lt;/i&gt;&lt;sup&gt;&lt;i&gt;MUT&lt;/i&gt;&lt;/sup&gt;, 1 was &lt;i&gt;TP53&lt;/i&gt; &lt;sup&gt;&lt;i&gt;MUT&lt;/i&gt;&lt;/sup&gt;. CR+VGPR occurred in 37/59 participants (62.7%) at cycle 7, 28/45 (62.2%) at cycle 12, and 21/39 (53.8%) at month 18 (Figure 1A). The median follow-up was 18 months (1.4–42.4). Both 24-month OS and PFS were 97.6% (95% CI: 93%–100%), 1 participant died at 15 months unrelated to treatment. On univariate analysis, &lt;i&gt;CXCR4&lt;/i&gt;&lt;sup&gt;&lt;i&gt;MUT&lt;/i&gt;&lt;/sup&gt; was not associated with inferior CR+VGPR rate at 1 year (&lt;i&gt;p&lt;/i&gt; = 0.10). Grade 3/4 treatment-related adverse events (TRAE) occurred in 31/63 participants during combination therapy, most common being neutropenia (&lt;i&gt;n&lt;/i&gt; = 23) and thrombocytopenia (&lt;i&gt;n&lt;/i&gt; = 3). During monotherapy, 13/59 participants had a grade 3/4 TRAE, 6 of whom had neutropenia. MRD negativity (threshold of 10&lt;sup&gt;−6&lt;/sup&gt;) in PB was 82% at cycle 7, 91% at cycle 12 and 71% at month 18. MRD negativity in BM was not as frequent but increased in BM over time (9% at cycle 7, 12% at cycle 12 and 23% at month 18). MRD negativity rates at cycles 7 and 12 were similar in those with and without &lt;i&gt;CXCR4&lt;/i&gt;&lt;sup&gt;&lt;i&gt;MUT&lt;/i&gt;&lt;/sup&gt; and &lt;i&gt;MYD88&lt;/i&gt;&lt;sup&gt;&lt;i&gt;WT&lt;/i&gt;&lt;/sup&gt; (Figure 1B). Log reductions of MRD in PB and BM in high-risk subsets were also comparable to corresponding non-high risk subsets.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Fixed duration BR and acalabrutinib was effective and well-tolerated. This regimen achieves amongst the highest CR+VGPR rates seen in frontline WM trials. Acknowledging sample size limitations, high-risk sub","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70093_54","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300397","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":"TREATMENT OF NEWLY-DIAGNOSED FOLLICULAR LYMPHOMA WITH RITUXIMAB, GOLCADOMIDE +/- NIVOLUMAB- INTERIM ANALYSIS OF THE PHASE II TOP-FLOR STUDY","authors":"A. Martynchyck,&nbsp;G. Chong,&nbsp;A. Barraclough,&nbsp;S. Ratnasingam,&nbsp;T. Marconi,&nbsp;J. B. Palmer,&nbsp;C. Keane,&nbsp;S. T. B. Lee,&nbsp;A. M. Scott,&nbsp;A. Romano,&nbsp;L. Churilov,&nbsp;D. Lee,&nbsp;E. A. Hawkes","doi":"10.1002/hon.70094_230","DOIUrl":"https://doi.org/10.1002/hon.70094_230","url":null,"abstract":"&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Standard rituximab (R) +lenalidomide (R2) or chemoimmunotherapy is effective in treatment-naïve follicular lymphoma (TN FL) but is associated with Grade 3–4 AE rates &gt; 65% with elderly patients (pts) overrepresented. Golcadomide (Golca) is a potent first-in-class oral Cereblon E3 Ligase Modulator (CELMoD) with dual immunomodulatory and anti-tumor activity 10- to 100-fold enhanced compared to lenalidomide, preferential lymphoid organ distribution and a favourable toxicity profile (Chavez ASH 2024; Amzallag ASH 2024). R-Golca yields responses in 93% relapsed FL. We have demonstrated immune augmentation, safety and efficacy of PD1/PDL1i nivolumab (N) +rituximab, and atezolizumab-obinutuzumab-radiotherapy in TN FL (Chong ASCO 2024; Barraclough Blood Adv 2025). We describe here the interim analysis of a randomised phase II study of R-Golca +/- N in stage II-IV, Grade 1–3A TN FL. (Chong ASCO 2024)&lt;/p&gt;&lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; TOP-FLOR (NCT05788081) is an investigator-led multicentre randomised open label umbrella Baysian Optimal Phase II trial in TN FL. Up to 40pts will be randomised 1:1 to receive 8 cycles of induction therapy Q4W: R (375 mg/m&lt;sup&gt;2&lt;/sup&gt; IV, D1), Golca (0.4 mg p.o daily, D1–14) +/- N (480 mg IV, D1) and 2 years of R maintenance (Q12W). The primary endpoint is rate of Complete Metabolic Response (CMR) in the absence of cessation due to prohibitive toxicity (CTCAE V5.0) following induction. Interim efficacy analysis (PET/CT Lugano response) in the first 22 pts was pre-planned, with a predefined futility threshold of 7/11 CMR (63.6%) in each arm.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; The interim analysis included 22 enrolled pts (11 per arm). Median age was 64.5y (range 49–77) with 68% male. CMR rate at the end of induction was 82% (18/22; 95% CI: 60%, 95%), CMR rate by arm in the futility cohort, was: 10/11 (92%) R-Golca and 8/11 (73%) R-Golca+N with 1 permanently ceasing due to Gr4 sepsis in cycle 1, unrelated to therapy and 1 ceasing due to disease progression (Figure 1). Proportion of pts experiencing an AE during induction were: 100% Gr1, 82% Gr2, 64% Gr3, 9% Gr4 (2pt). Most frequent of any grade were infection (77%; 95% CI: 54%–92% [Gr3 14%]), neutrophil count decrease (63%; 95% CI: 40–82% [Gr3+ 92%; plus 2 pt Gr3 febrile neutropenia]; 10pts received G-CSF) and maculo-papular rash (45%; 95% CI: 24%–67%—all in pts who had bactrim &amp; allopurinol which resolved on cessation of allopurinol); 2 pts R-Golca +N arm and 1 pt in the R-Golca arm had Golca dose reduction to 0.3 mg due to adverse events. 18/22 remain on treatment. Interim results reached the threshold for continued recruitment in both arms.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; This is the first study to demonstrate that Rituximab-golcadomide +/-nivolumab is a highly effective combination therapy in TN FL with manageable toxicity, most commonly neutropenia and infection. Differences between arms could not be elucidated in this preplanned interim analysis. The study continues recruit","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70094_230","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300392","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}