I. Y. Gong, M. Marinoni, M. Azab, T. Aoki, S. Bhella, C. Chen, R. Kridel, V. Kukreti, A. Prica, A. Vijenthira, C. Yang, D. Hodgson, N. Malik, D. Rodin, W. Wells, M. Crump, J. Kuruvilla
{"title":"在cd19 car - t细胞治疗时代，原发性难治性和早期复发大b细胞淋巴瘤患者的预后较差","authors":"I. Y. Gong, M. Marinoni, M. Azab, T. Aoki, S. Bhella, C. Chen, R. Kridel, V. Kukreti, A. Prica, A. Vijenthira, C. Yang, D. Hodgson, N. Malik, D. Rodin, W. Wells, M. Crump, J. Kuruvilla","doi":"10.1002/hon.70094_311","DOIUrl":null,"url":null,"abstract":"<p><b>Introduction:</b> Although early relapse in relapsed/refractory (R/R) large B cell lymphoma (LBCL) is associated with worse outcomes, the definition of primary refractory disease (PRD) has varied. This study aimed to evaluate the association of time to relapse (TTR) on the trajectory of second line (2L) treatments and outcomes.</p><p><b>Methods:</b> This retrospective study included pts aged ≥ 18 with R/R LBCL at Princess Margaret Cancer Centre (2017–2024, follow-up 01/25). TTR was categorized as PRD (progression during or at end of 1L treatment or < 3 mos), early relapse within 3–12, 12–24, or ≥ 24 mos of 1L rituximab-based therapy. Univariate and multivariable Cox regression analyses assessed the association between TTR and overall survival (OS) and progression-free survival (PFS) from first (OS1, PFS1) and second progression (OS2). Covariates included age, diagnosis, rIPI, and LDH.</p><p><b>Results:</b> Of 367 pts (median age 61, 63% male) included, pts with PRD were more likely to have HGBL and GCB subtype. There were no significant differences in characteristics between relapse groups at first progression (Table 1). For 2L treatment, 86% received platinum-based salvage chemotherapy (SC), and 48% underwent ASCT. Response rates were significantly higher in TTR ≥ 24 mos (81%) compared to PRD (50%), 3–12 mos (60%), and 12–24 mos (68%) (<i>p</i> < 0.001). At median follow-up of 41 mos, 245 (67%) of pts progressed, and 154 (42%) died. The 5-y OS1 was 45%; median OS1 for PRD and early relapse (3–12 mos) was 23 and 24 months, respectively, compared to not reached for relapse ≥ 24 mos (12–24 mos 56 mos). Cox analysis showed PRD and early relapse ≤ 12 mos were associated with inferior OS1 and PFS1 (OS1: PRD aHR 3.8: 95% CI: 2.1–7.2, <i>p</i> < 0.001; 3–12 mos aHR 3.3: 1.7–6.5, <i>p</i> < 0.001), while 12–24 mos was not (aHR 1.7: 0.7–4.1, <i>p</i> = 0.25) (Figure 1). Sensitivity analysis in de novo LBCL pts did not change these findings. Of the 245 patients who progressed after 2L, 120 (49%) had PRD after 1L. PRD and early relapse were associated with refractoriness to 2L treatment (92% and 67%, vs. 50%; <i>p</i> < 0.001). The 5-y OS2 was 34% (median 14 mos). Cox analysis showed PRD and early relapse were associated with worse OS2 compared to ≥ 24 mos (PRD aHR 2.3: 1.3–4.3, <i>p</i> = 0.008; 3–12 mos aHR 2.0: 1.0–3.8, <i>p</i> = 0.043; 12–24 mos aHR 1.4: 0.6–3.5, <i>p</i> = 0.43) (Figure 2). For 3L treatment, 215 pts were considered for CAR-T (85% apheresed), and 154 (72%) were CAR-T infused. Multivariable analysis showed the combined cohort of pts with PRD/early relapse < 12 mos was associated with worse OS2 compared to relapse > 12 mos (aHR 2.2: 1.1–4.4, <i>p</i> = 0.022; mOS2 for early relapse 31 mos vs. NR for late relapse).</p><p><b>Conclusions:</b> Our study shows that early relapse, particularly pts with PRD, continues to be associated with inferior outcomes even with 3L CAR-T. The association of relapsing timing on 2L CAR-T outcomes in an unselected population requires further investigation. Improved 1L treatments are needed to address outcome disparities in this high risk pt group.</p><p><b>Keywords:</b> Aggressive B-cell non-Hodgkin lymphoma</p><p><b>Potential sources of conflict of interest:</b></p><p><b>A. Prica</b></p><p><b>Honoraria:</b> Abbvie, Roche and Astra-Zeneca.</p><p><b>J. Kuruvilla</b></p><p><b>Consultant or advisory role:</b> Abbvie, BMS, Gilead, Merck, Roche, Seattle Genetics, OmniaBio</p><p><b>Honoraria:</b> Abbvie, Amgen, Astra Zeneca, BMS, Gilead, Incyte, Janssen, Karyopharm, Merck, Novartis, Pfizer, Roche</p><p><b>Other remuneration:</b> DSMB: Karyopharm</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_311","citationCount":"0","resultStr":"{\"title\":\"OUTCOMES OF PATIENTS WITH PRIMARY REFRACTORY AND EARLY RELAPSING LARGE B CELL LYMPHOMA ARE INFERIOR IN THE CD19 CAR T CELL THERAPY ERA\",\"authors\":\"I. Y. Gong, M. Marinoni, M. Azab, T. Aoki, S. Bhella, C. Chen, R. Kridel, V. Kukreti, A. Prica, A. Vijenthira, C. Yang, D. Hodgson, N. Malik, D. Rodin, W. Wells, M. Crump, J. 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引用次数: 0
摘要
虽然复发/难治性（R/R）大B细胞淋巴瘤（LBCL）的早期复发与较差的预后相关，但原发性难治性疾病（PRD）的定义各不相同。本研究旨在评估复发时间（TTR）与二线（2L）治疗轨迹和结果的关系。方法：本回顾性研究纳入玛格丽特公主癌症中心（2017-2024）年龄≥18岁的R/R LBCL患者（1月25日随访）。TTR被归类为PRD（在1L治疗期间或结束时进展）；在1L利妥昔单抗治疗的3 - 12、12-24或≥24个月内早期复发。单因素和多变量Cox回归分析评估了TTR与首次（OS1, PFS1）和第二次进展（OS2）的总生存期（OS）和无进展生存期（PFS）之间的关系。协变量包括年龄、诊断、rIPI和LDH。结果：在367名患者（中位年龄61岁，63%为男性）中，PRD患者更有可能患有HGBL和GCB亚型。复发组在首次进展时的特征无显著差异（表1）。对于2L治疗，86%的患者接受了基于铂的补救性化疗（SC）， 48%的患者接受了ASCT。TTR≥24个月（81%）的缓解率显著高于PRD（50%）、3-12个月（60%）和12-24个月（68%）(p <；0.001)。在41个月的中位随访中，245名（67%）患者进展，154名（42%）患者死亡。5-y OS1为45%；PRD和早期复发（3-12个月）的中位OS1分别为23个月和24个月，而未达到复发≥24个月（12-24个月，56个月）。Cox分析显示，PRD和早期复发≤12 mos与较差的OS1和PFS1相关(OS1: PRD aHR 3.8: 95% CI: 2.1-7.2, p <；0.001;3-12个最大aHR 3.3: 1.7-6.5, p <；0.001)，而12-24个大多数没有（aHR 1.7: 0.7-4.1, p = 0.25）（图1）。对新发LBCL患者的敏感性分析没有改变这些发现。在245例2L后进展的患者中，120例（49%）在1L后出现PRD。PRD和早期复发与2L治疗的难治性相关(92%和67%，vs. 50%；p & lt;0.001)。5-y OS2为34%（中位14个）。Cox分析显示，与≥24 mos相比，PRD和早期复发与更差的OS2相关(PRD aHR 2.3: 1.3-4.3, p = 0.008；3 ~ 12岁的aHR 2.0: 1.0 ~ 3.8, p = 0.043；12-24岁的aHR为1.4:0.6-3.5,p = 0.43)（图2）。在3L治疗中，215名患者被考虑接受CAR-T治疗（85%的患者接受CAR-T治疗），154名患者（72%）接受CAR-T输注治疗。多变量分析显示合并PRD/早期复发和lt的患者队列；与复发相比，12例患者伴有更差的OS2；12个mos (aHR 2.2: 1.1 ~ 4.4, p = 0.022；早期复发用mOS2（31个，晚期复发用NR）。结论：我们的研究表明，早期复发，特别是PRD患者，即使使用3L CAR-T治疗，仍然与较差的预后相关。在未选择的人群中，复发时间与2L CAR-T结果的关联需要进一步研究。需要改进1L治疗来解决这一高危人群的预后差异。关键词：侵袭性b细胞非霍奇金淋巴瘤潜在利益冲突来源PricaHonoraria：艾伯维（Abbvie）、罗氏（Roche）和阿斯特拉- zeneca。顾问或顾问角色：艾伯维、BMS、吉利德、默克、罗氏、西雅图基因、OmniaBioHonoraria：艾伯维、安进、阿斯特拉-利康、BMS、吉利德、Incyte、杨森、Karyopharm、默克、诺华、辉瑞、罗彻其他薪酬：DSMB: Karyopharm
OUTCOMES OF PATIENTS WITH PRIMARY REFRACTORY AND EARLY RELAPSING LARGE B CELL LYMPHOMA ARE INFERIOR IN THE CD19 CAR T CELL THERAPY ERA
Introduction: Although early relapse in relapsed/refractory (R/R) large B cell lymphoma (LBCL) is associated with worse outcomes, the definition of primary refractory disease (PRD) has varied. This study aimed to evaluate the association of time to relapse (TTR) on the trajectory of second line (2L) treatments and outcomes.
Methods: This retrospective study included pts aged ≥ 18 with R/R LBCL at Princess Margaret Cancer Centre (2017–2024, follow-up 01/25). TTR was categorized as PRD (progression during or at end of 1L treatment or < 3 mos), early relapse within 3–12, 12–24, or ≥ 24 mos of 1L rituximab-based therapy. Univariate and multivariable Cox regression analyses assessed the association between TTR and overall survival (OS) and progression-free survival (PFS) from first (OS1, PFS1) and second progression (OS2). Covariates included age, diagnosis, rIPI, and LDH.
Results: Of 367 pts (median age 61, 63% male) included, pts with PRD were more likely to have HGBL and GCB subtype. There were no significant differences in characteristics between relapse groups at first progression (Table 1). For 2L treatment, 86% received platinum-based salvage chemotherapy (SC), and 48% underwent ASCT. Response rates were significantly higher in TTR ≥ 24 mos (81%) compared to PRD (50%), 3–12 mos (60%), and 12–24 mos (68%) (p < 0.001). At median follow-up of 41 mos, 245 (67%) of pts progressed, and 154 (42%) died. The 5-y OS1 was 45%; median OS1 for PRD and early relapse (3–12 mos) was 23 and 24 months, respectively, compared to not reached for relapse ≥ 24 mos (12–24 mos 56 mos). Cox analysis showed PRD and early relapse ≤ 12 mos were associated with inferior OS1 and PFS1 (OS1: PRD aHR 3.8: 95% CI: 2.1–7.2, p < 0.001; 3–12 mos aHR 3.3: 1.7–6.5, p < 0.001), while 12–24 mos was not (aHR 1.7: 0.7–4.1, p = 0.25) (Figure 1). Sensitivity analysis in de novo LBCL pts did not change these findings. Of the 245 patients who progressed after 2L, 120 (49%) had PRD after 1L. PRD and early relapse were associated with refractoriness to 2L treatment (92% and 67%, vs. 50%; p < 0.001). The 5-y OS2 was 34% (median 14 mos). Cox analysis showed PRD and early relapse were associated with worse OS2 compared to ≥ 24 mos (PRD aHR 2.3: 1.3–4.3, p = 0.008; 3–12 mos aHR 2.0: 1.0–3.8, p = 0.043; 12–24 mos aHR 1.4: 0.6–3.5, p = 0.43) (Figure 2). For 3L treatment, 215 pts were considered for CAR-T (85% apheresed), and 154 (72%) were CAR-T infused. Multivariable analysis showed the combined cohort of pts with PRD/early relapse < 12 mos was associated with worse OS2 compared to relapse > 12 mos (aHR 2.2: 1.1–4.4, p = 0.022; mOS2 for early relapse 31 mos vs. NR for late relapse).
Conclusions: Our study shows that early relapse, particularly pts with PRD, continues to be associated with inferior outcomes even with 3L CAR-T. The association of relapsing timing on 2L CAR-T outcomes in an unselected population requires further investigation. Improved 1L treatments are needed to address outcome disparities in this high risk pt group.
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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