R. Merryman, D. S. Wallace, R. Redd, H. A. Walker, R. Tringale, V. Kats, A. Sigmund, I. E. Ahn, A. Bessnow, J. R. Brown, J. L. Crombie, M. S. Davids, D. C. Fisher, C. K. Hahn, E. D. Jacobsen, C. A. Jacobson, A. I. Kim, A. S. LaCasce, O. O. Odejide, E. M. Parry, D. Qualls, C. E. Ryan, A. Sekar, S. Devata, C. Casulo, K. Maddocks, M. Murakami, P. Armand, Y. Sawalha
{"title":"RITUXIMAB AND EPCORITAMAB AS FIRST-LINE THERAPY FOR PATIENTS WITH HIGH-TUMOR BURDEN FOLLICULAR LYMPHOMA: FIRST RESULTS OF A MULTICENTER PHASE II TRIAL","authors":"R. Merryman, D. S. Wallace, R. Redd, H. A. Walker, R. Tringale, V. Kats, A. Sigmund, I. E. Ahn, A. Bessnow, J. R. Brown, J. L. Crombie, M. S. Davids, D. C. Fisher, C. K. Hahn, E. D. Jacobsen, C. A. Jacobson, A. I. Kim, A. S. LaCasce, O. O. Odejide, E. M. Parry, D. Qualls, C. E. Ryan, A. Sekar, S. Devata, C. Casulo, K. Maddocks, M. Murakami, P. Armand, Y. Sawalha","doi":"10.1002/hon.70094_227","DOIUrl":null,"url":null,"abstract":"<p>R. Merryman and D. S. Wallace equally contributing author.</p><p><b>Introduction:</b> Patients (pts) with follicular lymphoma (FL) would benefit from chemotherapy-free frontline treatments that provide high response rates, durable remissions, and a favorable safety profile. Epcoritamab (epco) is a CD3xCD20 bispecific antibody (BsAb) approved in multiply relapsed FL where it results in high overall response rates (ORRs). In other settings, debulking therapy before BsAb treatment appears to reduce the risk of cytokine release syndrome (CRS). We hypothesized that treatment with rituximab (R) for debulking before initiation of full dose epco could lower the risk of CRS and deepen responses based on its distinct mechanism of targeting CD20. Here we present the first results of a phase 2 multicenter trial (NCT05783609) of time-limited therapy with R+epco.</p><p><b>Methods:</b> Eligibility criteria include: age ≥ 18, stage II-IV, grade 1–3A FL, requirement for therapy based on modified GELF criteria, and ECOG PS 0–2. In cycle 1 (C1), pts receive 4 weekly doses of R (D −14, −7, 1, 8) and weekly subcutaneous epco on D1 (0.16 mg), D8 (0.8 mg), and D15/D22 (48 mg). Epco is dosed weekly in C2–3 and biweekly in C4–9. After 26 pts enrolled, a 3<sup>rd</sup> epco step-up dose (D15, 3 mg) was added and inpatient observation for C1D15 was no longer required. Responses are evaluated based on Lugano 2014 criteria after 2, 5, and 9 cycles.</p><p><b>Results:</b> As of 1/31/2025, 31 of 35 planned pts had enrolled. The median age was 57 (range 28–78). At study entry, 30 pts (97%) had stage III/IV, 8 (26%) bulky disease (≥ 7 cm), 7 (23%) grade 3A FL, and 17 (55%) a FLIPI score of 3–5.</p><p>Among 25 response-evaluable pts (6 pts awaiting 1st response assessment), the best ORR and complete metabolic response (CMR) rates were 100% and 92%, respectively. Rapid responses were observed (22 CMRs, 3 partial metabolic responses [PMRs] after 2 cycles of therapy). 1 PMR subsequently converted to a CMR and the other 2 pts have not yet been restaged. With a median follow-up of 6.0 months (m) (range 0–17.6), no pts have relapsed, yielding a 6 m PFS estimate of 100%.</p><p>Among 31 safety-evaluable pts, the most common adverse events (AEs) were CRS (48%; G1 39%; G2 6%, no G3+), fatigue (39%), injection site reactions (39%; G1 35%, G2 3%), and infections (39%; G1 6%, G2 23%, G3 10%). G3 infections include bacteremia, COVID-19, and lung infection. In each case, the infection resolved and the pt restarted study treatment. Other common grade 3+ AEs included neutropenia (16%) and lymphocytopenia (6%). 3 pts discontinued treatment due to an AE (persistent G1 rhinovirus, recurrent G1-G2 viral respiratory infections, G3 eosinophilia). All 3 pts were in a CMR at the time of treatment discontinuation.</p><p><b>Conclusion:</b> R+epco achieves high CMR rates in patients with high tumor burden FL, and debulking therapy with R may lower the risk of grade 2+ CRS. Based on these encouraging results, a 65-pt expansion cohort (total n = 100) is planned. Response and safety data for additional pts will be reported at the meeting.</p><p><b>Research</b> <b>funding declaration:</b> Research funding for the investigator-sponsored trial provided by Genmab/Abbvie</p><p><b>Keywords:</b> immunotherapy; indolent non-Hodgkin lymphoma</p><p><b>Potential sources of conflict of interest:</b></p><p><b>R. Merryman</b></p><p><b>Consultant or advisory role:</b> DG Medicine, Bristol Myers Squibb, KITE, Abbvie, Ipsen</p><p><b>Honoraria:</b> Abvvie, Genmab</p><p><b>Other remuneration:</b> Research funding: Bristol Myers Squibb, Abbvie/Genmab, Genentech/Roche</p><p><b>I. E. Ahn</b></p><p><b>Consultant or advisory role:</b> AstraZeneca, BeiGene, Lilly</p><p><b>Other remuneration:</b> research funding from BeiGene and Lilly</p><p><b>A. Bessnow</b></p><p><b>Consultant or advisory role:</b> Genmab</p><p><b>J. R. Brown</b></p><p><b>Employment or leadership position:</b> ASH Secretary</p><p><b>Consultant or advisory role:</b> Abbvie, Acerta/Astra-Zeneca, Alloplex Biotherapeutics, BeiGene, Bristol-Myers Squibb, EcoR1, Galapagos NV, Genentech/Roche, Grifols Worldwide Operations, InnoCare Pharma Inc, Loxo/Lilly, Magnet Biomedicine, Merck, Pharmacyclics</p><p><b>Other remuneration:</b> research funding from BeiGene, iOnctura, Loxo/Lilly, Nagoon Therapeutics</p><p><b>J. L. Crombie</b></p><p><b>Consultant or advisory role:</b> Genentech/Roche, Genmab, Abbvie, Regeneron, ADC Therapeutics, Lilly, Novartis, BMS</p><p><b>Other remuneration:</b> Research Funding: Genentech/Roche, Merck, Abbvie, Bayer</p><p><b>M. S. Davids</b></p><p><b>Consultant or advisory role:</b> AbbVie, Ascentage Pharma, Adaptive Biotechnologies, AstraZeneca, BeiGene, Bristol-Myers Squibb, Eli Lilly, Galapagos, Genentech, Genmab, Janssen, Merck, MEI Pharma, Nuvalent, Schrödinger, SecuraBio, Takeda, TG Therapeutics</p><p><b>Other remuneration:</b> UpToDate (royalties); Ascentage Pharma, MEI Pharma, Novartis (research support)</p><p><b>E. D. Jacobsen</b></p><p><b>Consultant or advisory role:</b> Ipsen, Daiichi, BMS, Bayer</p><p><b>C. A. Jacobson</b></p><p><b>Consultant or advisory role:</b> Kite/Gilead, BMS, Novartis, ADC Therapeutics, Abbvie, AstraZeneca, Janssen, Appia Bio, Aleta, Umoja, Kyverna, Miltenyi, Caribou, Galapagos, Sana, Synthekine, GenmAb, Genentech, Autolus.</p><p><b>A. S. LaCasce</b></p><p><b>Consultant or advisory role:</b> Genmab, Kite and Pierre Fabre.</p><p><b>D. Qualls</b></p><p><b>Consultant or advisory role:</b> ADC therapeutics, Genmab, and Bristol Myers Squibb</p><p><b>C. E. Ryan</b></p><p><b>Consultant or advisory role:</b> AstraZeneca</p><p><b>Other remuneration:</b> Research funding paid to institution: BeiGene, Genentech, Lilly</p><p><b>A. Sekar</b></p><p><b>Stock ownership:</b> Vertex Pharmaceuticals</p><p><b>S. Devata</b></p><p><b>Stock ownership:</b> AstraZeneca, Novo Nordisk, Glaxo smith Kline, Abbvie, J&J, Eli LIlly, Merck, Pfizer, Bayer</p><p><b>C. Casulo</b></p><p><b>Consultant or advisory role:</b> BMS, Abbvie, Genentech/Roche, Genmab</p><p><b>Honoraria:</b> BMS, Abbvie, Genentech/Roche, Genmab</p><p><b>Other remuneration:</b> Research fundings—Genmab, Gilead, Genentech.</p><p><b>K. Maddocks</b></p><p><b>Consultant or advisory role:</b> AstraZeneca, ADC Therapeutics, Autolous, BMS, Caribou, Genmab, Genentech, Incyte, Kite/Gilead, Lilly</p><p><b>M. Murakami</b></p><p><b>Consultant or advisory role:</b> CancerModels.org</p><p><b>Other remuneration:</b> Research funding from Genentech/Roche, Kite/Gilead.</p><p><b>P. Armand</b></p><p><b>Consultant or advisory role:</b> Merck, BMS/Celgene, ADC Therapeutics, GenMab, Enterome, Genentech/Roche, ATB Therapeutics, Foresight, Regeneron, Stelexis</p><p><b>Other remuneration:</b> Research funding: Kite. Institutional Research funding: Merck, BMS/Celgene, Adaptive, Genentech, IGM, AstraZeneca</p><p><b>Y. Sawalha</b></p><p><b>Consultant or advisory role:</b> ADC, AbbVie, Genmab</p><p><b>Honoraria:</b> Genentech</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_227","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hematological Oncology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/hon.70094_227","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
R. Merryman and D. S. Wallace equally contributing author.
Introduction: Patients (pts) with follicular lymphoma (FL) would benefit from chemotherapy-free frontline treatments that provide high response rates, durable remissions, and a favorable safety profile. Epcoritamab (epco) is a CD3xCD20 bispecific antibody (BsAb) approved in multiply relapsed FL where it results in high overall response rates (ORRs). In other settings, debulking therapy before BsAb treatment appears to reduce the risk of cytokine release syndrome (CRS). We hypothesized that treatment with rituximab (R) for debulking before initiation of full dose epco could lower the risk of CRS and deepen responses based on its distinct mechanism of targeting CD20. Here we present the first results of a phase 2 multicenter trial (NCT05783609) of time-limited therapy with R+epco.
Methods: Eligibility criteria include: age ≥ 18, stage II-IV, grade 1–3A FL, requirement for therapy based on modified GELF criteria, and ECOG PS 0–2. In cycle 1 (C1), pts receive 4 weekly doses of R (D −14, −7, 1, 8) and weekly subcutaneous epco on D1 (0.16 mg), D8 (0.8 mg), and D15/D22 (48 mg). Epco is dosed weekly in C2–3 and biweekly in C4–9. After 26 pts enrolled, a 3rd epco step-up dose (D15, 3 mg) was added and inpatient observation for C1D15 was no longer required. Responses are evaluated based on Lugano 2014 criteria after 2, 5, and 9 cycles.
Results: As of 1/31/2025, 31 of 35 planned pts had enrolled. The median age was 57 (range 28–78). At study entry, 30 pts (97%) had stage III/IV, 8 (26%) bulky disease (≥ 7 cm), 7 (23%) grade 3A FL, and 17 (55%) a FLIPI score of 3–5.
Among 25 response-evaluable pts (6 pts awaiting 1st response assessment), the best ORR and complete metabolic response (CMR) rates were 100% and 92%, respectively. Rapid responses were observed (22 CMRs, 3 partial metabolic responses [PMRs] after 2 cycles of therapy). 1 PMR subsequently converted to a CMR and the other 2 pts have not yet been restaged. With a median follow-up of 6.0 months (m) (range 0–17.6), no pts have relapsed, yielding a 6 m PFS estimate of 100%.
Among 31 safety-evaluable pts, the most common adverse events (AEs) were CRS (48%; G1 39%; G2 6%, no G3+), fatigue (39%), injection site reactions (39%; G1 35%, G2 3%), and infections (39%; G1 6%, G2 23%, G3 10%). G3 infections include bacteremia, COVID-19, and lung infection. In each case, the infection resolved and the pt restarted study treatment. Other common grade 3+ AEs included neutropenia (16%) and lymphocytopenia (6%). 3 pts discontinued treatment due to an AE (persistent G1 rhinovirus, recurrent G1-G2 viral respiratory infections, G3 eosinophilia). All 3 pts were in a CMR at the time of treatment discontinuation.
Conclusion: R+epco achieves high CMR rates in patients with high tumor burden FL, and debulking therapy with R may lower the risk of grade 2+ CRS. Based on these encouraging results, a 65-pt expansion cohort (total n = 100) is planned. Response and safety data for additional pts will be reported at the meeting.
Researchfunding declaration: Research funding for the investigator-sponsored trial provided by Genmab/Abbvie
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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