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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 在BGD化疗前短期(x3)纳武单抗可提高复发/难治性霍奇金淋巴瘤的缓解率:波兰淋巴瘤研究组的N-BURGUND试验
IF 3.3 4区 医学
Hematological Oncology Pub Date : 2025-06-17 DOI: 10.1002/hon.70094_357
J. M. Zaucha, E. Paszkiewicz-Kozik, M. Taszner, B. Małkowski, J. Rybka, K. Chromik, A. Kołkowska-Leśniak, E. Subocz, Ł. Targoński, P. Ceklarz, M. Witkowska, K. Domańska-Czyż, A. Giza, R. Swoboda, M. Kobylecka, C. Voltin, J. Romejko-Jarosińska, M. Świerkowska, B. Ostrowska, A. Druzd-Sitek, M. Kurlapski, M. Bednarek, G. Romanowicz, J. Góra-Tybor, J. Hałka, T. Wróbel, S. Giebel, G. Helbig, E. Lech-Marańda
{"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, E. Paszkiewicz-Kozik, M. Taszner, B. Małkowski, J. Rybka, K. Chromik, A. Kołkowska-Leśniak, E. Subocz, Ł. Targoński, P. Ceklarz, M. Witkowska, K. Domańska-Czyż, A. Giza, R. Swoboda, M. Kobylecka, C. Voltin, J. Romejko-Jarosińska, M. Świerkowska, B. Ostrowska, A. Druzd-Sitek, M. Kurlapski, M. Bednarek, G. Romanowicz, J. Góra-Tybor, J. Hałka, T. Wróbel, S. Giebel, G. Helbig, E. Lech-Marańda","doi":"10.1002/hon.70094_357","DOIUrl":"https://doi.org/10.1002/hon.70094_357","url":null,"abstract":"<p><b>Introduction</b>: 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., <i>Hematological Oncology</i>, 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 <i>having hypothesized</i> 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.</p><p><b>Methods:</b> 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<sub>NIV</sub> and 2 to max four cycles of BGD (bendamustine 90 mg/m<sup>2</sup> D1,2; gemcitabine 800 mg/m<sup>2</sup> on D1,4; dexamethasone 40 mg on D1–4) combined with CD34+ cell mobilization followed by PET<sub>2BGD</sub>. 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<sub>BGD</sub>-negativity response in patients after two cycles of BGD. The secondary endpoints are PET<sub>NIVO</sub> response and the results of circulating tumor DNA assessment at the time of PET examinations.</p><p><b>Results</b>: 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 (< 12 months), whereas the remaining 21 (24%) had a late relapse. All patients have completed 3 × N and 2 × BGD. Eighty-four PET<sub>NIVO,</sub> and 78 PET<sub>BGD</sub> results were available at the time of submission. The PET<sub>NIVO</sub> negativity rate was 34%. Afterward, the PET<sub>BGD</sub> 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.</p><p><b>Conclusion:</b> 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}
引用次数: 0
Current Status of Revisions to the Lugano Classification in Lymphoma 淋巴瘤Lugano分类的修订现状
IF 3.3 4区 医学
Hematological Oncology Pub Date : 2025-06-17 DOI: 10.1002/hon.70103
The Organizing Committee of the Lugano Classification Workshop
{"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}
引用次数: 0
FIXED DURATION TREATMENT OF BENDAMUSTINE-RITUXIMAB AND ACALABRUTINIB IN FRONTLINE WALDENSTROM’S MACROGLOBULINEMIA: DEEP MOLECULAR RESPONSES IN HIGH-RISK PATIENT SUBSETS 苯达莫司汀-利妥昔单抗和阿卡鲁替尼治疗一线华登斯特罗姆的巨球蛋白血症:高危患者亚群的深层分子反应
IF 3.3 4区 医学
Hematological Oncology Pub Date : 2025-06-17 DOI: 10.1002/hon.70093_54
A. Suleman, K. Roos, K. Mangoff, Y. Jiang, G. Klein, D. Villa, D. MacDonald, M. Aljama, M. Shafey, N. Forward, J. Larouche, A. Nikonova, M. Sebag, I. Sandhu, S. Chow, R. McClure, M. Gallucci, H. Simmons, G. Tomlinson, N. L. Berinstein
{"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}
引用次数: 0
TREATMENT OF NEWLY-DIAGNOSED FOLLICULAR LYMPHOMA WITH RITUXIMAB, GOLCADOMIDE +/- NIVOLUMAB- INTERIM ANALYSIS OF THE PHASE II TOP-FLOR STUDY 利妥昔单抗、golcadomide +/- nivolumab治疗新诊断滤泡性淋巴瘤——ii期顶层研究的中期分析
IF 3.3 4区 医学
Hematological Oncology Pub Date : 2025-06-17 DOI: 10.1002/hon.70094_230
A. Martynchyck, G. Chong, A. Barraclough, S. Ratnasingam, T. Marconi, J. B. Palmer, C. Keane, S. T. B. Lee, A. M. Scott, A. Romano, L. Churilov, D. Lee, E. A. Hawkes
{"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}
引用次数: 0
EPCORITAMAB MONOTHERAPY DEMONSTRATES DEEP AND DURABLE RESPONSES AT 3-YEAR FOLLOW-UP IN PATIENTS WITH RELAPSED/REFRACTORY FOLLICULAR LYMPHOMA 在复发/难治性滤泡性淋巴瘤患者的3年随访中,Epcoritamab单药治疗显示出深刻和持久的反应
IF 3.3 4区 医学
Hematological Oncology Pub Date : 2025-06-17 DOI: 10.1002/hon.70094_240
K. M. Linton, J. M. Vose, W. Jurczak, P. J. Lugtenburg, E. Gyan, J. C. Chavez, A. Sureda, J. H. Christensen, H. Tilly, R. Córdoba, D. J. Lewis, M. Hutchings, M. Roost Clausen, J. Sancho, T. Cochrane, S. Leppä, M. E. D. Chamuleau, C. Thieblemont, P. F. Caimi, Y. H. Karimi, C. Andreadis, K. Izutsu, N. Fukuhara, E. Favaro, P. Patah, M. Geybels, I. Altintaş, C. Morehouse, U. Vitolo
{"title":"EPCORITAMAB MONOTHERAPY DEMONSTRATES DEEP AND DURABLE RESPONSES AT 3-YEAR FOLLOW-UP IN PATIENTS WITH RELAPSED/REFRACTORY FOLLICULAR LYMPHOMA","authors":"K. M. Linton,&nbsp;J. M. Vose,&nbsp;W. Jurczak,&nbsp;P. J. Lugtenburg,&nbsp;E. Gyan,&nbsp;J. C. Chavez,&nbsp;A. Sureda,&nbsp;J. H. Christensen,&nbsp;H. Tilly,&nbsp;R. Córdoba,&nbsp;D. J. Lewis,&nbsp;M. Hutchings,&nbsp;M. Roost Clausen,&nbsp;J. Sancho,&nbsp;T. Cochrane,&nbsp;S. Leppä,&nbsp;M. E. D. Chamuleau,&nbsp;C. Thieblemont,&nbsp;P. F. Caimi,&nbsp;Y. H. Karimi,&nbsp;C. Andreadis,&nbsp;K. Izutsu,&nbsp;N. Fukuhara,&nbsp;E. Favaro,&nbsp;P. Patah,&nbsp;M. Geybels,&nbsp;I. Altintaş,&nbsp;C. Morehouse,&nbsp;U. Vitolo","doi":"10.1002/hon.70094_240","DOIUrl":"https://doi.org/10.1002/hon.70094_240","url":null,"abstract":"&lt;p&gt;&lt;b&gt;Introduction:&lt;/b&gt; Epcoritamab (epcor), a subcutaneous (SC) CD3xCD20 bispecific antibody, is approved for relapsed/refractory (R/R) follicular lymphoma (FL) after ≥ 2 prior lines of therapy (3L+) based on EPCORE NHL-1 FL (NCT03625037; US/EU; Linton KM, et al. &lt;i&gt;Lancet Haem&lt;/i&gt; 2024;11:E593–E605) and NHL-3 FL (NCT04542824; Japan) expansion cohorts (EXP) results. NHL-1 cycle (C) 1 optimization cohort (OPT) implemented a 3-step-up dosing (3-SUD) regimen to support outpatient utilization of epcor in FL. We report 3-y follow-up (FU) from EXP and updated OPT results for epcor monotherapy in patients (pts) with 3L+ FL.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; Pts with CD20+ R/R FL grade[G] 1–3A and ≥ 2 prior lines of systemic treatment (tx) received SC epcor in 28-d Cs until disease progression or unacceptable toxicity. NHL-1 (&lt;i&gt;N&lt;/i&gt; = 128) and NHL-3 (&lt;i&gt;N&lt;/i&gt; = 21) EXP were pooled for diversity; OPT is reported separately. For EXP, the primary endpoint was efficacy; secondary endpoints were minimal residual disease (ClonoSeq®) negativity and safety. Due to the disproportionate impact of COVID-19 pandemic on pts from EXP, sensitivity analyses with conservative adjustment for COVID-19 deaths were conducted for efficacy. For OPT, the primary endpoint was incidence and severity of cytokine release syndrome (CRS); secondary endpoints were response rates and safety.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; As of Dec 2024, median FU was 35 mo and 15.5 mo and median duration of tx was 9.7 mo and 11.4 mo in EXP(&lt;i&gt;N&lt;/i&gt; = 149) and OPT(&lt;i&gt;N&lt;/i&gt; = 86), respectively. Across cohorts, pts were heavily pretreated (median 3 prior lines) and had high-risk R/R FL features. In the pooled EXP, overall response rate (ORR) was 84.6% and complete response rate (CRR) was 67.1% (Table).&lt;/p&gt;&lt;p&gt;With longer-term FU, safety from EXP was generally consistent with previous reports. In EXP, conducted during the COVID-19 pandemic peak, 34.9% of pts had G3–4 infections (18.1% COVID-19) and 7.4% had G5 events (5.4% COVID-19). 28% of pts discontinued (d/c) tx due to tx-emergent adverse events (TEAEs; 12.1% COVID-19). G3 or higher infections were reported in 14.3% of pts on ≥ 2y of tx (&lt;i&gt;n&lt;/i&gt; = 35).&lt;/p&gt;&lt;p&gt;In OPT, updated ORR/CRR were 91.9%/73.3%; time-to-event endpoint data were still maturing, with most pts alive (93%).&lt;/p&gt;&lt;p&gt;With additional FU, safety from OPT remained unchanged from prior reports of only low-grade CRS (39.5% G1 and 9.3% G2) and no immune effector cell-associated neurotoxicity syndrome (ICANS). In OPT, conducted post COVID-19 pandemic peak, 20.9% of pts had G3–4 infections (7.0% COVID-19, all G3); 1 pt had G5 TEAE of viral respiratory tract infection. TEAEs leading to tx d/c occurred in 11% (1.2% COVID).&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Epcor monotherapy demonstrated deep and durable responses and manageable safety with no new safety signals at 3y in a large and diversified 3L+ FL global population. OPT cohort results show response rates consistent with those in EXP and confirm the favorable safety profi","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_240","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300165","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}
引用次数: 0
TARGETED IMMUNOTHERAPY IN CHILDREN, ADOLESCENTS, AND YOUNG ADULTS WITH NEWLY DIAGNOSED CLASSICAL HODGKIN LYMPHOMA, A SINGLE CENTER EXPERIENCE 靶向免疫治疗儿童,青少年和年轻人新诊断经典霍奇金淋巴瘤,单中心经验
IF 3.3 4区 医学
Hematological Oncology Pub Date : 2025-06-17 DOI: 10.1002/hon.70093_34
M. S. Cairo, J. Hochberg, K. Klose, J. Basso, A. Gardenswartz, A. Flower, S. Braniecki, L. Harrison
{"title":"TARGETED IMMUNOTHERAPY IN CHILDREN, ADOLESCENTS, AND YOUNG ADULTS WITH NEWLY DIAGNOSED CLASSICAL HODGKIN LYMPHOMA, A SINGLE CENTER EXPERIENCE","authors":"M. S. Cairo,&nbsp;J. Hochberg,&nbsp;K. Klose,&nbsp;J. Basso,&nbsp;A. Gardenswartz,&nbsp;A. Flower,&nbsp;S. Braniecki,&nbsp;L. Harrison","doi":"10.1002/hon.70093_34","DOIUrl":"https://doi.org/10.1002/hon.70093_34","url":null,"abstract":"&lt;p&gt;&lt;b&gt;Introduction:&lt;/b&gt; Despite excellent survival outcomes, significant chronic health conditions occur among pediatric, adolescent, and young adult classical Hodgkin lymphoma (cHL) survivors as a result of current chemotherapy and radiation regimens. Targeting both the tumor microenvironment as well as tumor-specific antigens have been proven to be effective and safe treatments for cHL patients. Here we report on our Hodgkin Lymphoma immunotherapy approach over the past 13 yrs. We have combined the use of the antibody-drug conjugate brentuximab vedotin (Bv) to target reed-sternberg cells along with the anti-CD20 antibody rituximab (RTX) and checkpoint inhibitor nivolumab (N) targeting the immune microenvironment added to risk-adapted chemotherapy in newly diagnosed CAYA cHL patients. This chemoimmunotherapy approach may allow for anthracycline dose reduction and radiation sparing in intermediate and high risk patients.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; All patients received 2 cycles of Bv, doxorubicin, vinblastine, dacarbazine, and RTX (Bv-AVD-R). Early response utilizing FDG-PET scan was performed following 2 cycles of therapy (PET2) with PET2 negativity defined as Deauville score of 1, 2 or 3. Rapid early responders (RER) or slow early responders (SER) received an additional 2 to 6 cycles of treatment based on risk assignment and early response. After our initial protocol completed enrollment, subsequent patients were enrolled on our follow up study evaluating the addition of nivolumab beginning with cycle 3 therapy without further anthracycline (Bv-NVD-R). This limited the total anthracycline dose to 100 mg/m&lt;sup&gt;2&lt;/sup&gt; per patient. Radiation therapy initially was planned for high risk patients with SER and subsequently on our current study only for patients not achieving metabolic CR by FDG-PET at the completion of all therapy.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; A total of 48 patients have completed therapy with a median age of 17 years (4–23 years), Thirty four patients received Bv-AVD-R for all cycles and 14 patients have been enrolled on our follow up study receiving Bv-AVD-R followed by Bv-NVD-R. All 48 patients achieved a complete response to therapy for a CR rate of 100%. Early PET2 negativity was achieved in 42 patients (87.5%). Due to excellent rapid response, only four patients have required radiation therapy. The EFS and OS is 100% with a median follow up time of &gt; 90 months (range 4–159 months) (Fig 1). Accrual is ongoing for our current trial. We have completed the nivolumab saftey run in. There have been no unexpected adverse events related to therapy and no dose limiting toxicities with the addition of nivolumab to our immunochemotherapy backbone.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; The addition of immunotherapy to a reduced chemotherapy backbone is safe, effective and well tolerated. Targeting the HRS cell as well as the tumor microenvironment and PD1/PD-L1 axis is a promising approach in CAYA with cHL and may allow for reduction in anthracycline and radia","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_34","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300448","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}
引用次数: 0
HISTOLOGICAL CHARACTERISTICS, TREATMENT PATTERNS, AND OUTCOMES FOLLOWING DISEASE PROGRESSION AFTER CAR-T THERAPY IN RELAPSED/REFRACTORY FOLLICULAR LYMPHOMA 复发/难治性滤泡性淋巴瘤car-t治疗后疾病进展的组织学特征、治疗模式和结果
IF 3.3 4区 医学
Hematological Oncology Pub Date : 2025-06-16 DOI: 10.1002/hon.70094_250
A. Rivas-Delgado, H. S. Raman, M. Kabat, N. Glaubach, M. Corona, E. Luttwak, L. Falchi, J. Lue, M. Scordo, A. D. Zelenetz, M. Perales, G. L. Shah, J. H. Park, S. Ringelstein-Harlev, O. Beyar-Katz, L. A. Leslie, A. Ip, P. Armand, C. A. Jacobson, M. L. Palomba, R. Shouval, R. W. Merryman, G. Salles
{"title":"HISTOLOGICAL CHARACTERISTICS, TREATMENT PATTERNS, AND OUTCOMES FOLLOWING DISEASE PROGRESSION AFTER CAR-T THERAPY IN RELAPSED/REFRACTORY FOLLICULAR LYMPHOMA","authors":"A. Rivas-Delgado,&nbsp;H. S. Raman,&nbsp;M. Kabat,&nbsp;N. Glaubach,&nbsp;M. Corona,&nbsp;E. Luttwak,&nbsp;L. Falchi,&nbsp;J. Lue,&nbsp;M. Scordo,&nbsp;A. D. Zelenetz,&nbsp;M. Perales,&nbsp;G. L. Shah,&nbsp;J. H. Park,&nbsp;S. Ringelstein-Harlev,&nbsp;O. Beyar-Katz,&nbsp;L. A. Leslie,&nbsp;A. Ip,&nbsp;P. Armand,&nbsp;C. A. Jacobson,&nbsp;M. L. Palomba,&nbsp;R. Shouval,&nbsp;R. W. Merryman,&nbsp;G. Salles","doi":"10.1002/hon.70094_250","DOIUrl":"https://doi.org/10.1002/hon.70094_250","url":null,"abstract":"&lt;p&gt;H. S. Raman equally contributing author.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Introduction:&lt;/b&gt; CD19-directed CAR T-cell therapy (CAR-T) has demonstrated outstanding therapeutic activity in patients (pts) with refractory/relapsed (R/R) follicular lymphoma (FL). However, data regarding histological features, treatment patterns, and outcomes of pts with disease progression (POD) following CD19 CAR-T therapy for R/R are poorly understood.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; Characteristics of 101 pts receiving CAR-T for FL were collected across 4 international centers. Pts with FL grade 3B or any prior history of histological transformation were excluded.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; We identified 25 pts (24.8%) who experienced POD after CAR-T. Median age at infusion was 62 years (range 34–79). Pre CAR-T FL grade was 1–2 in 76% of the pts, grade 3A in 12%, and unavailable in 12%. Median prior therapy lines were 3 (range 2–7). Administered products were axicabtagene ciloleucel (84%), tisagenlecleucel (12%), and lisocabtagene maraleucel (4%), predominantly as SOC (96%). High-risk features before CAR-T were common: 40% had experienced POD24, 68% were refractory to their last therapy, including 32% with primary refractory disease. Among pts with post-CAR-T POD, the best post-infusion response was CR in 56%, PR in 20%, and stable or progressive disease in 24%. The median time from CAR-T infusion to POD was 8.9 months (IQR 3–15).&lt;/p&gt;&lt;p&gt;Following POD, 20 pts received systemic therapy (median 1 line, range 1–7), 3 remain on active surveillance, 1 received palliative care, and 1 was lost to follow-up. The ORR after initial post-POD therapy was 72% among evaluable pts. Administered therapies included CD3×CD20 bispecific antibodies (BsAbs) (&lt;i&gt;n&lt;/i&gt; = 10; 8 evaluable, ORR 88%, CR 63%), chemoimmunotherapy (&lt;i&gt;n&lt;/i&gt; = 6, ORR 83%, CR 50%), tafasitamab-based combinations (lenalidomide, &lt;i&gt;n&lt;/i&gt; = 1; tazemetostat, &lt;i&gt;n&lt;/i&gt; = 1; no response), lenalidomide + obinutuzumab (&lt;i&gt;n&lt;/i&gt; = 1; no response), and investigational agent (&lt;i&gt;n&lt;/i&gt; = 1; ORR 100%). Three pts underwent allogeneic SCT as consolidation and are still in remission.&lt;/p&gt;&lt;p&gt;In 18 pts with post-CAR-T POD histologic documentation, 3 had transformed FL to diffuse large B-cell lymphoma, 1 had FL grade 3B, and 14 had relapsed FL grade 1–3A. CD19-negative disease was found in 1 pt, while 5 (28%) had CD20-negative disease (3 pre-CAR-T exposed to CD3xCD20 BsAb).&lt;/p&gt;&lt;p&gt;Median follow-up for the entire cohort and from POD was 24 and 16 months, respectively. Median progression-free survival post CAR-T POD was 19 months (95% CI: 10–28) with an estimated 1-year PFS of 68% (95% CI: 50–91). During follow-up, 5 pts (18%) died, all due to disease progression. Median overall survival from POD was not reached, with an estimated 1-y OS of 86% (95% CI: 73–100) (Figure).&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; To our knowledge, this represents the largest cohort of FL pts with POD post-CAR-T. BsAbs showed promise in this setting, but longer follow-up is needed for durability assessment. ","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_250","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299566","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}
引用次数: 0
CD3XCD20 BISPECIFIC ANTIBODIES IN TRANSFORMED WALDENSTRÖM MACROGLOBULINEMIA/LYMPHOPLASMACYTIC LYMPHOMA 转化waldenstrÖm巨球蛋白血症/淋巴浆细胞性淋巴瘤中的Cd3xcd20双特异性抗体
IF 3.3 4区 医学
Hematological Oncology Pub Date : 2025-06-16 DOI: 10.1002/hon.70094_264
M. Brocard, D. Roos-Weil, L. Kanagaratnam, L. Bussot, B. Papoular, C. Tomowiak, S. Chevreux, G. Crochet, T. Vaugeois, E. Toussaint, A. Quinquenel, P. Kapoor, E. Durot
{"title":"CD3XCD20 BISPECIFIC ANTIBODIES IN TRANSFORMED WALDENSTRÖM MACROGLOBULINEMIA/LYMPHOPLASMACYTIC LYMPHOMA","authors":"M. Brocard,&nbsp;D. Roos-Weil,&nbsp;L. Kanagaratnam,&nbsp;L. Bussot,&nbsp;B. Papoular,&nbsp;C. Tomowiak,&nbsp;S. Chevreux,&nbsp;G. Crochet,&nbsp;T. Vaugeois,&nbsp;E. Toussaint,&nbsp;A. Quinquenel,&nbsp;P. Kapoor,&nbsp;E. Durot","doi":"10.1002/hon.70094_264","DOIUrl":"https://doi.org/10.1002/hon.70094_264","url":null,"abstract":"&lt;p&gt;&lt;b&gt;Introduction:&lt;/b&gt; Patients with histological transformation (HT) of Waldenström macroglobulinemia (WM) who relapse or are refractory (R/R) have a poor prognosis, especially those who are not eligible or relapsing after high-dose chemotherapy with autologous stem cell transplant (ASCT) and/or chimeric antigen receptor (CAR) T-cell therapy. CD3xCD20 bispecific monoclonal antibodies (BsAb) (epcoritamab, glofitamab) provide overall and complete responses of around 60% and 40%, respectively, in R/R diffuse large-cell B lymphomas (DLBCL). However, these therapies have not been evaluated in HT of WM. The aim of this study was to evaluate the efficacy and safety of CD3xCD20 BsAb in patients with R/R transformed WM.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; We retrospectively identified patients with biopsy-proven transformed WM/lymphoplasmacytic lymphoma treated with epcoritamab or glofitamab in FILO/LYSA centers and an American center. The primary endpoint was best overall response rate (ORR). Secondary endpoints were best complete response rate (CRR), progression free-survival (PFS), overall survival (OS) and safety. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded according to the ASTCT 2019 criteria. Hematological toxicity and infections were graded according to NCI CTCAE (version 5.0).&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Between February 2023 and July 2024, 12 patients with R/R transformed WM were treated with BsAb (6 glofitamab and 6 epcoritamab). Median age at WM diagnosis was 72 years (range 43–83). Patients received a median of 1 prior line of treatment (range, 0–6) for WM, including 4 treated with a BTK inhibitor (2 with ibrutinib, 1 with zanubritinib and 1 received both successively). 4 patients had concurrent diagnosis of WM and DLBCL. For the others, the median time from WM to HT was 5.3 years (range, 0.4–12.8) and 15 months (range, 1–48) from HT diagnosis to BsAb. Patients had received a median of 2 prior lines (range, 1–5) for HT. Five patients were previously treated with CAR T-cell, including 2 with prior ASCT. At the time of BsAb, 75% of patients were refractory to the last treatment, and 67% to at least 2 consecutive lines. The median age was 80 years (range, 45–86). Patient treated with glofitamab had received a median of 9 cycles (6–12) and those treated with epcoritamab a median of 3 cycles (2–6). Best ORR was 92% and best CRR was 42%. CRS occurred in 10 patients (83%, with only 1 grade 3) and ICANS in 2 patients (17%, no grade 3–4). Seven patients (58%) presented infections, including 4 grade 3. After a median follow-up of 9.4 months (95% CI: 4–23), the 6-months PFS and OS were 57% (95% CI: 34%–94%) and 75% (95% CI: 54%–100%), respectively. Five deaths were reported, 3 due to disease progression and 2 from infection.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusion:&lt;/b&gt; This study shows an interesting efficacy of CD3xCD20 BsAb in R/R transformed WM in a population of elderly and heavily pre-treated patients, without unexpected","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_264","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299563","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}
引用次数: 0
THE EFFECT OF TP53 MUTATIONS ON THE LOCAL RESPONSE OF MANTLE CELL LYMPHOMA TO RADIATION THERAPY tp53突变对套细胞淋巴瘤放射治疗局部反应的影响
IF 3.3 4区 医学
Hematological Oncology Pub Date : 2025-06-16 DOI: 10.1002/hon.70094_268
A. Deshane, J. Yahalom, N. A. Wijetunga, A. Kumar, B. Fregonese, A. Zelenetz, G. Salles, B. S. Imber
{"title":"THE EFFECT OF TP53 MUTATIONS ON THE LOCAL RESPONSE OF MANTLE CELL LYMPHOMA TO RADIATION THERAPY","authors":"A. Deshane,&nbsp;J. Yahalom,&nbsp;N. A. Wijetunga,&nbsp;A. Kumar,&nbsp;B. Fregonese,&nbsp;A. Zelenetz,&nbsp;G. Salles,&nbsp;B. S. Imber","doi":"10.1002/hon.70094_268","DOIUrl":"https://doi.org/10.1002/hon.70094_268","url":null,"abstract":"&lt;p&gt;&lt;b&gt;Introduction:&lt;/b&gt; The role for radiotherapy (RT) in mantle cell lymphoma (MCL) is limited as MCL often presents in advanced stages. A broader role may be rational given MCL’s propensity for profound but inconsistent radiosensitivity. Common molecular alterations in MCL impact prognosis, namely TP53 mutations (TP53mut). TP53mut can influence systemic therapy choices but its impact on radiosensitivity, or RT decision making is unclear. Better understanding could guide precision radiotherapy.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; We analyzed patients (pts) treated with RT for MCL from 2010 to 2024, focusing on a cohort with next generation sequencing (NGS) for somatic genetic alterations (&lt;i&gt;n&lt;/i&gt; = 66). Age and stage at RT, treatment intent, relapsed status, site of RT, and prior systemic therapy were collected. Sites treated in pts with TP53mut versus without TP53mut (TP53wt) were compared. Lesion SUV and diameter, extranodal (EN) status of the treated site, blastoid histology, RT dose, and metabolic response at first assessment were compared. Additionally, sites receiving very low dose radiotherapy (VLDRT, 4 Gy) and sites of local failure (LF) were analyzed.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; 66 patients were identified, treated to 97 sites. 84 sites (87%) were treated in the relapsed setting. 54 sites (56%) were localized relapsed or early-stage disease. By site, median follow up after RT was 1.5 years. 61 sites (64%) treated were EN. Median RT dose was 30 Gy (4–40 Gy), median lesion diameter was 3.5 cm (0.9–22 cm), and median SUV max was 7.5 (0–61.6). 80% (&lt;i&gt;n&lt;/i&gt; = 77) of sites had available PET response assessment at a median of 1.7 months (0.1–7.1) post-RT. Overall response rate (ORR) was 98.7%, and complete response (CR) rate (CRR) was 81% (&lt;i&gt;n&lt;/i&gt; = 62). 32% of pts (&lt;i&gt;n&lt;/i&gt; = 21) treated to 33 sites (34%) harbored TP53mut. ORR and CRR were 100% and 83% in TP53wt and 96% and 80% in TP53mut. RT dose (&lt;i&gt;p&lt;/i&gt; = 0.817) and CR% (&lt;i&gt;p&lt;/i&gt; = 0.491) did not differ by TP53 status. When analyzed by site, TP53mut had significantly worse 1-year FFLP than TP53wt (100 % vs. 85%; &lt;i&gt;p&lt;/i&gt; = 0.002). 6 sites overall (6.2%) had LF; of note, 4 of 6 sites received only 4 Gy. TP53mut status was associated with higher risk of LF (&lt;i&gt;p&lt;/i&gt; = 0.024). Analysis of sites treated to 4 Gy (&lt;i&gt;n&lt;/i&gt; = 14; 14.4%) revealed that TP53mut remained associated with increased risk of LF (&lt;i&gt;p&lt;/i&gt; = 0.002). For sites receiving &gt; 4 Gy (&lt;i&gt;n&lt;/i&gt; = 83; Median dose 30 Gy, Range 10–40 Gy), presence of TP53mut (&lt;i&gt;n&lt;/i&gt; = 30) suggested association with FFLP, though not signficant (&lt;i&gt;p&lt;/i&gt; = 0.069). ORR and CRR was 100% and 82% for sites receiving &gt; 4 gy and 89% and 79% for sites receiving VLDRT.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; In this cohort of MCL treated with RT, response was excellent, and LF was rare. Most sites of LF received VLDRT. TP53mut was significantly associated with higher risk of LF in sites treated with 4 Gy. Despite excellent responses to RT at higher, definitive doses, sites of pts wi","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_268","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299530","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}
引用次数: 0
CLL18/MOIRAI TRIAL AIMING TO ESTABLISH MEASUREMENT OF INDIVIDUAL RESIDUAL DISEASE FOR ADJUSTMENT OF TREATMENT DURATION TO IMPROVE OUTCOMES IN TREATMENT-NAIVE CLL/SLL Cll18 / moirai试验旨在建立个体残留疾病的测量方法,以调整治疗时间,以改善治疗初治cll / sll的预后
IF 3.3 4区 医学
Hematological Oncology Pub Date : 2025-06-16 DOI: 10.1002/hon.70093_OT02
P. Cramer, O. Al-Sawaf, E. Görgen, L. Mazot, S. Robrecht, M. Schüler-Aparicio, C. Paulitschek, A. Zey, A. Albrecht, J. Blau, L. Jung, S. Reidel, F. Bosch, C. da Cuna Bang, M. Doubek, E. Feyzi, A. Fink, P. Ghia, M. Gregor, R. Guieze, K. Jamroziak, A. Janssens, A. P. Kater, S. Kersting, P. Langerbeins, M. Levin, V. Lindström, M. Mattsson, C. Niemann, A. Quinquenel, M. Ritgen, L. Scarfò, P. Staber, S. Stilgenbauer, T. Tadmor, P. Thornton, E. Tausch, L. Ysebaert, K. Fischer, B. F. Eichhorst, M. Hallek
{"title":"CLL18/MOIRAI TRIAL AIMING TO ESTABLISH MEASUREMENT OF INDIVIDUAL RESIDUAL DISEASE FOR ADJUSTMENT OF TREATMENT DURATION TO IMPROVE OUTCOMES IN TREATMENT-NAIVE CLL/SLL","authors":"P. Cramer,&nbsp;O. Al-Sawaf,&nbsp;E. Görgen,&nbsp;L. Mazot,&nbsp;S. Robrecht,&nbsp;M. Schüler-Aparicio,&nbsp;C. Paulitschek,&nbsp;A. Zey,&nbsp;A. Albrecht,&nbsp;J. Blau,&nbsp;L. Jung,&nbsp;S. Reidel,&nbsp;F. Bosch,&nbsp;C. da Cuna Bang,&nbsp;M. Doubek,&nbsp;E. Feyzi,&nbsp;A. Fink,&nbsp;P. Ghia,&nbsp;M. Gregor,&nbsp;R. Guieze,&nbsp;K. Jamroziak,&nbsp;A. Janssens,&nbsp;A. P. Kater,&nbsp;S. Kersting,&nbsp;P. Langerbeins,&nbsp;M. Levin,&nbsp;V. Lindström,&nbsp;M. Mattsson,&nbsp;C. Niemann,&nbsp;A. Quinquenel,&nbsp;M. Ritgen,&nbsp;L. Scarfò,&nbsp;P. Staber,&nbsp;S. Stilgenbauer,&nbsp;T. Tadmor,&nbsp;P. Thornton,&nbsp;E. Tausch,&nbsp;L. Ysebaert,&nbsp;K. Fischer,&nbsp;B. F. Eichhorst,&nbsp;M. Hallek","doi":"10.1002/hon.70093_OT02","DOIUrl":"https://doi.org/10.1002/hon.70093_OT02","url":null,"abstract":"&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; The two major options for the first-line therapy of chronic lymphocytic leukemia (CLL) are a continuous BTK inhibitor treatment given as long as possible for disease control, or a venetoclax-based fixed-duration treatment, which usually leads to deep responses and a treatment-free interval of several years. There is an increased use of fixed-duration venetoclax-based regimens, such as venetoclax plus obinutuzumab (12 cycles) or venetoclax plus ibrutinib or acalabrutinib with/without obinutuzumab. While these combination therapies are more intense compared to monotherapies, the treatment-free interval carries advantages in terms of quality of life, safety and costs. The goal of this phase-III trial is to evaluate if a more individualized, but time-limited treatment duration is beneficial.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; Two treatment arms have a fixed-duration and one arm evaluates a treatment duration based on measurable residual disease (MRD):&lt;/p&gt;&lt;p&gt;— the standard arm A is the established combination of venetoclax and obinutuzumab (Ven-Obi, 12 cycles with a duration of 28 days, Obi only during cycles 1–6),&lt;/p&gt;&lt;p&gt;— arm B evaluates venetoclax plus pirtobrutinib (Ven-Pirto) for 15 cycles (3 cycles pirtobrutinib alone, then 12 cycles combined with venetoclax), and&lt;/p&gt;&lt;p&gt;— in arm C, Ven-Pirto will be administered for at least 15 and up to 36 cycles (as long as there is a deepening of response) until achievement of undetectable MRD (uMRD). To facilitate the transfer to clinical routine, MRD is measured in peripheral blood, by multi-colour flow cytometry and with a cut-off of 10&lt;sup&gt;−4&lt;/sup&gt;. Two MRD assessments with an interval of 12 weeks both documenting uMRD are needed to allow for a treatment discontinuation and treatment will be continued for an additional 12 weeks after the second uMRD result as a consolidation.&lt;/p&gt;&lt;p&gt;813 patients with previously untreated CLL/SLL irrespective of age, comorbidities or CLL risk-factors will be recruited 1:1:1 to the three arms (271 each) with a stratification according to TP53 deletion and/or mutation, IGHV mutational status, disease type (CLL vs. SLL), and age. The primary endpoint is the investigator-assessed progression-free survival (PFS). The trial is designed to show both superiority of MRD-guided Ven-Pirto over Ven-Obi and over fixed duration Ven-Pirto. Secondary endpoints include iwCLL response, MRD, overall survival and safety parameters.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Recruitment is expected to start at the time of the ICML meeting. The estimated recruitment time of the 813 patients in approximately 160 sites in 16 countries is 20 months. Approximately 41 months after start of recruitment, a sufficient number of PFS events shall be reached for the primary endpoint analysis.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Summary/Conclusion:&lt;/b&gt; The CLL18/MOIRAI trial will address the question whether an individualized, MRD-guided first-line treatment with pirtobrutinib and venetoclax improves the outcome of patients with CLL/SLL compared ","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_OT02","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299628","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}
引用次数: 0
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