Ibrutinib With Bendamustine and Rituximab for Treatment of Patients With Relapsed/Refractory Aggressive B-Cell Lymphoma

IF 3.3 4区医学 Q2 HEMATOLOGY

Hematological Oncology Pub Date : 2024-11-21 DOI:10.1002/hon.70001

Meirav Kedmi, Elena Ribakovsy, Ohad Benjamini, Ginette Schiby, Iris Barshack, Stephen Raskin, Yael Eshet, Ramit Mehr, Netanel Horowitz, Ronit Gurion, Neta Goldschmidt, Chava Perry, Itai Levi, Ariel Aviv, Katrin Herzog-Tzarfati, Arnon Nagler, Abraham Avigdor

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引用次数: 0

Abstract

Therapy for relapsed or refractory (R/R) aggressive B-cell non-Hodgkin lymphoma (aB-NHL) post autologous stem cell transplantation (ASCT) or in elderly patients can be challenging. In this single-center, single-arm, phase II clinical study, we investigated the efficacy of ibrutinib (560 mg once daily) in combination with bendamustine and rituximab (IBR) given for six 28-day cycles in their standard dose, to patients with R/R aB-NHL who were either transplant ineligible in first or second relapse or post-ASCT for second relapse. The primary endpoint was overall response rate (ORR). Fifty-six patients (54% male, median age 69.7 years) were included. ORR was 49.1% among 55 patients treated with ≥ 1 cycle of IBR and 69.4% among 36 patients treated with ≥ 3 cycles. Patients with relapsed disease had significantly higher ORR compared to those with refractory disease (72.3% vs. 37.8%, p = 0.024). Median overall survival (OS) was 11.6 months (95% CI, 7.1–22.3) and median progression-free survival was 5.3 months (95% CI, 2.5–7.4). Patients with complete and partial responses had significantly longer median OS compared to those with stable and progressive disease (28.1 vs. 5.2 months, p < 0.0001). Adverse events included thrombocytopenia (19.6%), anemia (16.1%), neutropenia (7.1%), fatigue (35.7%), diarrhea (28.6%) and nausea (28.6%). At the first efficacy evaluation 8 patients were referred to transplantation, and 3 more were referred during follow-up. These data indicate that the IBR regimen is a safe and effective treatment option that can also be used for bridging to transplantation in patients with R/R aB-NHL.Trial Registration: ClinicalTrials.gov: NCT02747732

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伊布替尼联合苯达莫司汀和利妥昔单抗治疗复发/难治性侵袭性B细胞淋巴瘤患者

自体干细胞移植（ASCT）后或老年患者复发或难治（R/R）侵袭性B细胞非霍奇金淋巴瘤（aB-NHL）的治疗具有挑战性。在这项单中心、单臂、II期临床研究中，我们调查了伊布替尼（560毫克，每天一次）联合苯达莫司汀和利妥昔单抗（IBR）的疗效，伊布替尼联合苯达莫司汀和利妥昔单抗以标准剂量给药6个28天周期，用于首次或第二次复发不符合移植条件或ASCT后第二次复发的R/R aB-NHL患者。主要终点是总体反应率（ORR）。共纳入 56 名患者（54% 为男性，中位年龄为 69.7 岁）。55名患者接受了≥1个周期的IBR治疗，总反应率为49.1%；36名患者接受了≥3个周期的IBR治疗，总反应率为69.4%。与难治性疾病患者相比，复发性疾病患者的 ORR 明显更高（72.3% 对 37.8%，P = 0.024）。中位总生存期（OS）为11.6个月（95% CI，7.1-22.3），中位无进展生存期为5.3个月（95% CI，2.5-7.4）。与病情稳定和进展的患者相比，完全和部分应答患者的中位生存期明显更长（28.1个月 vs. 5.2个月，p < 0.0001）。不良反应包括血小板减少（19.6%）、贫血（16.1%）、中性粒细胞减少（7.1%）、疲劳（35.7%）、腹泻（28.6%）和恶心（28.6%）。在首次疗效评估时，有 8 名患者被转入移植，另有 3 名患者在随访期间被转入移植。这些数据表明，IBR疗法是一种安全有效的治疗方案，也可用于R/R aB-NHL患者的移植桥接：试验注册：ClinicalTrials.gov：NCT02747732

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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.