R. Tao, C. Liu, W. Zhang, J. Wan, Y. Ma, Y. Zhu, L. Ma, S. Tian, H. Ding
{"title":"pd-1抗体sintilimab联合pegaspargase和anlotinib治疗iv期NKTCL患者的疗效和安全性的多中心前瞻性研究","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":null,"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>Keywords:</b> aggressive T-cell non-Hodgkin lymphoma; combination therapies; immunotherapy</p><p>No potential sources of conflict of interest.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70094_400","citationCount":"0","resultStr":"{\"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\":null,\"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. 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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
Introduction: 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.
Methods: 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/m2 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.
Results: 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%, p < 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.
Conclusions: 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.
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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