Treatments and Outcomes of Newly Diagnosed CD5-Positive Diffuse Large B-Cell Lymphoma: A Multi-Institutional Observational Study

IF 3.9 4区医学 Q2 HEMATOLOGY Hematological Oncology Pub Date : 2025-02-12 DOI:10.1002/hon.70047

Yuma Nato, Kana Miyazaki, Dai Maruyama, Hiroyuki Takahashi, Kazutaka Sunami, Satsuki Murakami, Eiju Negoro, Yuri Miyazawa, Ilseung Choi, Takahiro Okada, Nobuyuki Takayama, Naoto Tomita, Shuji Momose, Yuto Kaneda, Masahiro Yoshida, Hiroshi Gomyo, Kohtaro Toyama, Momoko Nishikori, Akio Saito, Junji Hiraga, Taro Masunari, Naoki Takahashi, Junya Makiyama, Tomotaka Suzuki, Hiroko Tsunemine, Jun Takizawa, Takeharu Kato, Yasufumi Masaki, Noriko Fukuhara, Masataka Okamoto, Isao Tawara, Naoko Asano, Koichi Ohshima, Koji Izutsu, Koji Kato, Ritsuro Suzuki, Motoko Yamaguchi

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Abstract

CD5-positive diffuse large B-cell lymphoma (CD5+ DLBCL) is characterized by a poor prognosis and frequent central nervous system (CNS) relapse. Sandwich therapy comprising dose-adjusted (DA)-EPOCH-R (etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin, and rituximab) and high-dose methotrexate (HD-MTX) (DA-EPOCH-R/HD-MTX) showed excellent efficacy and manageable safety in a phase II study of patients diagnosed with stage II–IV CD5+ DLBCL. To validate the results of that study and elucidate the current state of treatment for CD5+ DLBCL, we retrospectively analyzed the outcomes of patients with CD5+ DLBCL diagnosed between 2016 and 2021 who received anthracycline-containing chemotherapy with rituximab. Among the 346 patients evaluated, 62 (18%) received DA-EPOCH-R/HD-MTX. The median follow-up time was 43 months. In 55 patients with stage II–IV disease treated with DA-EPOCH-R/HD-MTX, the 2-year overall survival (OS), progression-free survival, and cumulative incidence of CNS relapse were 87% (95% CI, 73%–94%), 76% (95% CI, 61%–86%), and 7.3% (95% CI, 2.4%–16%), respectively. There were no treatment-related deaths. Febrile neutropenia occurred in 18 (33%) patients. Multivariate analysis of the 346 patients identified elevated serum lactate dehydrogenase levels, multiple extranodal involvement, no intrathecal MTX (IT-MTX), and no DA-EPOCH-R/HD-MTX as independent risk factors for OS. Only one CNS relapse event was observed in 28 patients who received both HD-MTX and IT-MTX. Our study provides real-world data on the treatments and outcomes of a large number of patients. The favorable survival and manageable toxicity of DA-EPOCH-R/HD-MTX have been validated in clinical settings. The use of HD-MTX and IT-MTX might be effective for preventing CNS relapse in patients with CD5+ DLBCL.

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新诊断的 CD5 阳性弥漫大 B 细胞淋巴瘤的治疗方法和结果：多机构观察研究

CD5阳性弥漫性大b细胞淋巴瘤（CD5+ DLBCL）以预后差和中枢神经系统（CNS）频繁复发为特点。在一项II - iv期CD5+ DLBCL患者的II期研究中，由剂量调整(DA)-EPOCH-R（依托泊苷、强的松龙、新碱、环磷酰胺、阿霉素和利妥昔单抗）和高剂量甲氨蝶呤（HD-MTX）组成的夹心疗法显示出出色的疗效和可管理的安全性。为了验证该研究的结果并阐明CD5+ DLBCL的治疗现状，我们回顾性分析了2016年至2021年间诊断为CD5+ DLBCL的患者接受含蒽环类药物利妥昔单抗化疗的结果。在接受评估的346例患者中，62例（18%）接受了DA-EPOCH-R/HD-MTX治疗。中位随访时间为43个月。在55例接受DA-EPOCH-R/HD-MTX治疗的II-IV期疾病患者中，2年总生存率（OS）、无进展生存率（progression-free survival）和CNS累计复发发生率分别为87% （95% CI, 73%-94%）、76% （95% CI, 61%-86%）和7.3% （95% CI, 2.4%-16%）。没有与治疗相关的死亡。发热性中性粒细胞减少18例（33%）。346例患者的多因素分析发现血清乳酸脱氢酶水平升高，多发性结外受累，无鞘内MTX (IT-MTX)，无DA-EPOCH-R/HD-MTX是OS的独立危险因素。在接受HD-MTX和IT-MTX治疗的28例患者中，仅观察到1例中枢神经系统复发事件。我们的研究提供了大量患者治疗和结果的真实数据。DA-EPOCH-R/HD-MTX的良好生存和可控毒性已在临床环境中得到验证。使用HD-MTX和IT-MTX可能对预防CD5+ DLBCL患者中枢神经系统复发有效。

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来源期刊

Hematological Oncology 医学-血液学

CiteScore

4.20

自引率

6.10%

发文量

147

审稿时长

>12 weeks

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.