M. S. Davids, S. Robrecht, E. Tausch, S. Stilgenbauer, M. Choi, A. Skarbnik, C. Chyn Chua, L. Sivcheva, K. Kreuzer, M. Ritgen, T. Gaska, D. Heintel, C. Arrais-Rodrigues, R. Santucci Alves Da Silva, T. Illmer, Z. Liu, B. Chyla, W. Sinai, M. V. Pai, M. Porro Lurà, M. Hallek, B. Eichhorst, O. Al-Sawaf, K. Fischer
{"title":"正在进行的多中心二期临床研究的初步结果，该研究用维妥乐加奥比妥单抗（ReVenG）治疗复发性细胞白血病患者","authors":"M. S. Davids, S. Robrecht, E. Tausch, S. Stilgenbauer, M. Choi, A. Skarbnik, C. Chyn Chua, L. Sivcheva, K. Kreuzer, M. Ritgen, T. Gaska, D. Heintel, C. Arrais-Rodrigues, R. Santucci Alves Da Silva, T. Illmer, Z. Liu, B. Chyla, W. Sinai, M. V. Pai, M. Porro Lurà, M. Hallek, B. Eichhorst, O. Al-Sawaf, K. Fischer","doi":"10.1002/hon.70094_211","DOIUrl":null,"url":null,"abstract":"<p><b>Introduction:</b> Venetoclax (Ven)-based retreatment of patients (pts) with recurrent CLL after frontline Ven has not previously been studied prospectively. Here, we report an exploratory, interim analysis of the ongoing ReVenG trial, the first prospective study of Ven-Obinutuzumab (Obi) retreatment.</p><p><b>Methods:</b> CLL pts are eligible for this study (NCT04895436) if they received first-line (1L), time-limited Ven-based therapy, achieved response of ≥ 12 months (mo.) after completing therapy, then progressed and met iwCLL treatment criteria. Cohort-1 (Co-1, main cohort) includes pts with progressive (PD) > 2 years after completing 1L treatment (planned <i>N</i> = 60), and cohort-2 (Co-2, exploratory cohort) includes pts with PD 1 to 2 years post 1L therapy (planned <i>N</i> = 15). Both cohorts receive 6 cycles of Ven-Obi, with Co-1 receiving 12 total cycles of Ven, and Co-2 receiving at least 24 cycles of Ven. The primary endpoint is overall response rate (ORR) 3 mo. after the end of combination therapy (EOCT + 3 mo.) for Co-1. Key secondary endpoints include safety, additional response and MRD endpoints, and PFS.</p><p><b>Results:</b> At data cut-off of 18 October 2024, 25 of 75 pts (33%) were enrolled, 22 in Co-1 and 3 in Co-2. The median age was 67 years (range 41–84), with 76% Binet stage B or C. 32% had lymph nodes ≥ 5 cm at study entry. Median time to starting study treatment after last dose of 1L treatment was 53.3 mo. (range 19–90). 8/21 (38%) were either <i>TP53</i>mut and/or del(17p), and 18/21 (86%) tested were IGHV unmutated Of the 21 pts assessed at time of PD after FD treatment with Ven in 1L, none had acquired a mutation in <i>BCL-2</i>. With regard to efficacy in Co-1, all 15 pts who have reached EOCT + 3 mo. to date have achieved response, including 3 pts with CR/CRi, 2 pts in PR with radiographic CR awaiting marrow biopsy, and 10 pts with PR. At EOCT + 3 mo., 11 of 13 pts with samples available had undetectable MRD in the peripheral blood by NGS (<i>n</i> = 2 at 10<sup>−4</sup>, <i>n</i> = 3 at 10<sup>−5</sup>, <i>n</i> = 6 at 10<sup>−6</sup>). 7 pts have reached end of treatment + 3 mo., including 3 in CR and 4 in PR. With a median follow-up time on study of 10.3 mo., one pt has progressed, and all 25 pts are alive. In the safety analysis in all 25 pts, the most common AEs were neutropenia (44%, including 28% Gr 3/4), diarrhea (28%), nausea (24%) and infusion related reaction (24%). Serious AEs occurred in 32% of pts, including 1 pt each with sinusitis, pancytopenia, lower respiratory tract infection, COVID-19, and sepsis. There were no Gr 4 infections, fatal AEs, or tumor lysis syndrome (TLS). 3 pts (12%) had dose reduction of Ven due to AEs, including 1 each due to neutropenia, diarrhea, and nausea, and none discontinued Ven due to toxicity.</p><p><b>Conclusions:</b> In this interim analysis of the initial pts on ReVenG, efficacy was observed, and the safety of Ven-Obi in these relapsed pts was similar to prior studies. The study is actively accruing, and more pts with longer follow-up are needed to more completely assess Ven-Obi re-treatment.</p><p><b>Research</b> <b>funding declaration:</b> AbbVie, Roche/Genentech</p><p><b>Encore Abstract:</b> ASCO 2025; EHA 2025</p><p><b>Keywords:</b> molecular targeted therapies; combination therapies; chronic lymphocytic leukemia (CLL)</p><p><b>Potential sources of conflict of interest:</b></p><p><b>M. S. Davids</b></p><p><b>Consultant or advisory role:</b> AbbVie, Ascentage Pharma, AstraZeneca, BeiGene, Bristol-Myers Squibb, Eli Lilly, Galapagos, Genentech, Genmab, Janssen, Merck, MEI Pharma, Schrödinger</p><p><b>Other remuneration:</b> Research Support: Novartis, Ascentage Pharma, MEI Pharma; Authorship: UpToDate—royalties</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.9000,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70094_211","citationCount":"0","resultStr":"{\"title\":\"PRELIMINARY RESULTS OF THE ONGOING MULTICENTER, PHASE 2 STUDY OF RETREATMENT WITH VENETOCLAX PLUS OBINUTUZUMAB (ReVenG) IN PATIENTS WITH RECURRENT CLL\",\"authors\":\"M. S. Davids, S. Robrecht, E. Tausch, S. Stilgenbauer, M. Choi, A. Skarbnik, C. Chyn Chua, L. Sivcheva, K. Kreuzer, M. Ritgen, T. Gaska, D. Heintel, C. Arrais-Rodrigues, R. Santucci Alves Da Silva, T. Illmer, Z. Liu, B. Chyla, W. Sinai, M. V. Pai, M. Porro Lurà, M. Hallek, B. Eichhorst, O. Al-Sawaf, K. Fischer\",\"doi\":\"10.1002/hon.70094_211\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><b>Introduction:</b> Venetoclax (Ven)-based retreatment of patients (pts) with recurrent CLL after frontline Ven has not previously been studied prospectively. Here, we report an exploratory, interim analysis of the ongoing ReVenG trial, the first prospective study of Ven-Obinutuzumab (Obi) retreatment.</p><p><b>Methods:</b> CLL pts are eligible for this study (NCT04895436) if they received first-line (1L), time-limited Ven-based therapy, achieved response of ≥ 12 months (mo.) after completing therapy, then progressed and met iwCLL treatment criteria. Cohort-1 (Co-1, main cohort) includes pts with progressive (PD) > 2 years after completing 1L treatment (planned <i>N</i> = 60), and cohort-2 (Co-2, exploratory cohort) includes pts with PD 1 to 2 years post 1L therapy (planned <i>N</i> = 15). Both cohorts receive 6 cycles of Ven-Obi, with Co-1 receiving 12 total cycles of Ven, and Co-2 receiving at least 24 cycles of Ven. The primary endpoint is overall response rate (ORR) 3 mo. after the end of combination therapy (EOCT + 3 mo.) for Co-1. Key secondary endpoints include safety, additional response and MRD endpoints, and PFS.</p><p><b>Results:</b> At data cut-off of 18 October 2024, 25 of 75 pts (33%) were enrolled, 22 in Co-1 and 3 in Co-2. The median age was 67 years (range 41–84), with 76% Binet stage B or C. 32% had lymph nodes ≥ 5 cm at study entry. Median time to starting study treatment after last dose of 1L treatment was 53.3 mo. (range 19–90). 8/21 (38%) were either <i>TP53</i>mut and/or del(17p), and 18/21 (86%) tested were IGHV unmutated Of the 21 pts assessed at time of PD after FD treatment with Ven in 1L, none had acquired a mutation in <i>BCL-2</i>. With regard to efficacy in Co-1, all 15 pts who have reached EOCT + 3 mo. to date have achieved response, including 3 pts with CR/CRi, 2 pts in PR with radiographic CR awaiting marrow biopsy, and 10 pts with PR. At EOCT + 3 mo., 11 of 13 pts with samples available had undetectable MRD in the peripheral blood by NGS (<i>n</i> = 2 at 10<sup>−4</sup>, <i>n</i> = 3 at 10<sup>−5</sup>, <i>n</i> = 6 at 10<sup>−6</sup>). 7 pts have reached end of treatment + 3 mo., including 3 in CR and 4 in PR. With a median follow-up time on study of 10.3 mo., one pt has progressed, and all 25 pts are alive. In the safety analysis in all 25 pts, the most common AEs were neutropenia (44%, including 28% Gr 3/4), diarrhea (28%), nausea (24%) and infusion related reaction (24%). 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PRELIMINARY RESULTS OF THE ONGOING MULTICENTER, PHASE 2 STUDY OF RETREATMENT WITH VENETOCLAX PLUS OBINUTUZUMAB (ReVenG) IN PATIENTS WITH RECURRENT CLL
Introduction: Venetoclax (Ven)-based retreatment of patients (pts) with recurrent CLL after frontline Ven has not previously been studied prospectively. Here, we report an exploratory, interim analysis of the ongoing ReVenG trial, the first prospective study of Ven-Obinutuzumab (Obi) retreatment.
Methods: CLL pts are eligible for this study (NCT04895436) if they received first-line (1L), time-limited Ven-based therapy, achieved response of ≥ 12 months (mo.) after completing therapy, then progressed and met iwCLL treatment criteria. Cohort-1 (Co-1, main cohort) includes pts with progressive (PD) > 2 years after completing 1L treatment (planned N = 60), and cohort-2 (Co-2, exploratory cohort) includes pts with PD 1 to 2 years post 1L therapy (planned N = 15). Both cohorts receive 6 cycles of Ven-Obi, with Co-1 receiving 12 total cycles of Ven, and Co-2 receiving at least 24 cycles of Ven. The primary endpoint is overall response rate (ORR) 3 mo. after the end of combination therapy (EOCT + 3 mo.) for Co-1. Key secondary endpoints include safety, additional response and MRD endpoints, and PFS.
Results: At data cut-off of 18 October 2024, 25 of 75 pts (33%) were enrolled, 22 in Co-1 and 3 in Co-2. The median age was 67 years (range 41–84), with 76% Binet stage B or C. 32% had lymph nodes ≥ 5 cm at study entry. Median time to starting study treatment after last dose of 1L treatment was 53.3 mo. (range 19–90). 8/21 (38%) were either TP53mut and/or del(17p), and 18/21 (86%) tested were IGHV unmutated Of the 21 pts assessed at time of PD after FD treatment with Ven in 1L, none had acquired a mutation in BCL-2. With regard to efficacy in Co-1, all 15 pts who have reached EOCT + 3 mo. to date have achieved response, including 3 pts with CR/CRi, 2 pts in PR with radiographic CR awaiting marrow biopsy, and 10 pts with PR. At EOCT + 3 mo., 11 of 13 pts with samples available had undetectable MRD in the peripheral blood by NGS (n = 2 at 10−4, n = 3 at 10−5, n = 6 at 10−6). 7 pts have reached end of treatment + 3 mo., including 3 in CR and 4 in PR. With a median follow-up time on study of 10.3 mo., one pt has progressed, and all 25 pts are alive. In the safety analysis in all 25 pts, the most common AEs were neutropenia (44%, including 28% Gr 3/4), diarrhea (28%), nausea (24%) and infusion related reaction (24%). Serious AEs occurred in 32% of pts, including 1 pt each with sinusitis, pancytopenia, lower respiratory tract infection, COVID-19, and sepsis. There were no Gr 4 infections, fatal AEs, or tumor lysis syndrome (TLS). 3 pts (12%) had dose reduction of Ven due to AEs, including 1 each due to neutropenia, diarrhea, and nausea, and none discontinued Ven due to toxicity.
Conclusions: In this interim analysis of the initial pts on ReVenG, efficacy was observed, and the safety of Ven-Obi in these relapsed pts was similar to prior studies. The study is actively accruing, and more pts with longer follow-up are needed to more completely assess Ven-Obi re-treatment.
期刊介绍：
Hematological Oncology considers for publication articles dealing with experimental and clinical aspects of neoplastic diseases of the hemopoietic and lymphoid systems and relevant related matters. Translational studies applying basic science to clinical issues are particularly welcomed. Manuscripts dealing with the following areas are encouraged:
-Clinical practice and management of hematological neoplasia, including: acute and chronic leukemias, malignant lymphomas, myeloproliferative disorders
-Diagnostic investigations, including imaging and laboratory assays
-Epidemiology, pathology and pathobiology of hematological neoplasia of hematological diseases
-Therapeutic issues including Phase 1, 2 or 3 trials as well as allogeneic and autologous stem cell transplantation studies
-Aspects of the cell biology, molecular biology, molecular genetics and cytogenetics of normal or diseased hematopoeisis and lymphopoiesis, including stem cells and cytokines and other regulatory systems.
Concise, topical review material is welcomed, especially if it makes new concepts and ideas accessible to a wider community. Proposals for review material may be discussed with the Editor-in-Chief. Collections of case material and case reports will be considered only if they have broader scientific or clinical relevance.
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