Efficacy and safety of rituximab plus cladribine in patients with indolent B-cell lymphoma
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摘要: 目的:惰性非霍奇金淋巴瘤患者经多线治疗后对大剂量化疗的耐受性较差,最佳治疗方案仍有待探索。本研究旨在分析利妥昔单抗联合克拉屈滨(RC4)治疗初治和复发/难治性惰性B细胞非霍奇金淋巴瘤(B-NHL)的疗效及安全性。方法:回顾性分析2014年11月—2016年3月收治的19例使用RC4方案治疗的惰性B-NHL患者(2例华氏巨球蛋白血症,3例滤泡性淋巴瘤和14例边缘区B细胞淋巴瘤)的临床资料。RC4治疗方案为:在第1天使用375 mg/m2的利妥昔单抗,第2~5天使用克拉屈滨0.1 mg/(kg·d)。该方案每21 d重复一次,最多6个周期,评估该方案的疗效、不良事件和生存结果。结果:中位随访时间59.5个月(24~65.6个月),19例惰性B-NHL患者中6例(31.6%)获得完全缓解,10例(52.6%)获得部分缓解,客观缓解率为84.2%(16/19)。19例患者的中位无进展生存期和总生存期均未达到,预估的5年无进展生存率和总生存率分别为83.1%和89.2%。17例初治患者的中位无进展生存期和总生存期也未达到。克拉屈滨的主要不良事件为血液学毒性和免疫抑制,一半以上(63.2%,12/19)的患者出现肺部感染,没有患者发生自身免疫性溶血。结论:本研究表明RC4治疗对于初治和复发/难治性惰性B-NHL是有效且可耐受的治疗方案。Abstract: Objective: Patients with indolent non-Hodgkin's lymphoma usually require multi-line treatments and are less tolerant of high-dose chemotherapy. The best choice of treatment remains to be explored. In this study, we investigated the combination of rituximab and cladribine(RC4) therapy in the treatment of naive and relapse/refractory indolent B-cell non-Hodgkin's lymphoma(B-NHL) patients.Methods: We retrospectively analyzed the clinical data of 19 patients with indolent B-NHL(2 cases of Waldenstrom's macroglobulinemia, 3 cases of follicular lymphoma, and 14 cases of marginal zone B-cell lymphoma) treated between November 2014 and March 2016. RC4 treatment plan included rituximab 375 mg/m2 on day 1, and cladribine 0.1 mg/(kg·d) from day 2 to day 5. This plan was repeated every 21 days for a maximum of 6 cycles. We evaluated the treatment efficacy, adverse events and survival outcomes in the study.Results: The median follow-up time was 59.5 months(24 to 65.6 months). Among 19 patients with indolent B-NHL, 6 cases(31.6%) achieved complete response, 10 cases(52.6%) achieved partial response, and the objective response rate was 84.2%(16/19). The median progression-free survival(PFS) and overall survival(OS) were not reached, the estimated 5-year PFS rate and OS rate were 83.1% and 89.2% respectively. The median PFS and OS of 17 treatment-naive patients were also not reached. The main adverse events of cladribine were hematological toxicity and immunologic suppression. More than half of the patients(63.2%, 12/19) had pulmonary infection. There were no cases of autoimmune hemolysis.Conclusion: It suggests that RC4 treatment is an effective and well tolerated regimen in naive and relapse/refractory indolent B-NHL.
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Key words:
- cladribine /
- rituximab /
- indolent non-Hodgkin's lymphoma /
- marginal zone B-cell lymphoma
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[1] Swerdlow SH,Campo E,Pileri SA,et al.The 2016 revision of the World Health Organization classification of lymphoid neoplasms[J].Blood,2016,127(20):2375-2390.
[2] Van den Brand M,Scheijen B,Hess CJ,et al.Pathways towards indolent B-cell lymphoma-Etiology and therapeutic strategies[J].Blood Rev,2017,31(6):426-435.
[3] Suzuki R.Indolent B-cell lymphoma:the current standard in 2014[J].JCEH,2014,54(1):1-2.
[4] 黄耀慧,赵维莅.分子生物学时代T细胞淋巴瘤的治疗进展[J].临床血液学杂志,2020,33(9):589-593.
[5] 瞿敏,陶千山,安福润,等.CAR-T治疗复发难治B细胞淋巴瘤的安全性及临床疗效分析[J].临床血液学杂志,2019,32(7):521-526.
[6] Sehn LH.Introduction to a review series:the paradox of indolent B-cell lymphoma[J].Blood,2016,127(17):2045-2046.
[7] Kuruvilla J.The role of autologous and allogeneic stem cell transplantation in the management of indolent B-cell lymphoma[J].Blood,2016,127(17):2093-2100.
[8] Thieblemont C.Improved biological insight and influence on management in indolent lymphoma.Talk 3:update on nodal and splenic marginal zone lymphoma[J].Hematology Am Soc Hematol Educ Program,2017,2017(1):371-378.
[9] Freedman A.Follicular lymphoma:2018 update on diagnosis and management[J].Am J Hematol,2018,93(2):296-305.
[10] Chihara D,Arons E,Stetler-Stevenson M,et al.Randomized Phase II Study of First-Line Cladribine With Concurrent or Delayed Rituximab in Patients With Hairy Cell Leukemia[J].J Clin Oncol,2020,38(14):1527-1538.
[11] Puvvada SD,Guillen-Rodriguez J,Kumar A,et al.Phase 2 Open-Label Study of Bortezomib,Cladribine,and Rituximab in Advanced,Newly Diagnosed,and Relapsed/Refractory Mantle-Cell and Indolent Lymphomas[J].Clin Lymphoma Myeloma Leuk,2018,18(1):58-64.
[12] Sigal DS,Miller HJ,Schram ED,et al.Beyond hairy cell:the activity of cladribine in other hematologic malignancies[J].Blood,2010,116(16):2884-2896.
[13] Spurgeon S,Yu M,Phillips JD,et al.Cladribine:not just another purine analogue?[J].Expert Opin Investig Drugs,2009,18(8):1169-1181.
[14] International non-Hodgkin's lymphoma prognostic factors project.A predictive model for aggressive non-Hodgkin's lymphoma[J].N Engl J Med,1993,329(14):987-994.
[15] Morel P,Duhamel A,Gobbi P,et al.International prognostic scoring system for Waldenstrom macroglobulinemia[J].Blood,2009,113(18):4163-4170.
[16] Thieblemont C,Cascione L,Conconi A,et al.A MALT lymphoma prognostic index[J].Blood,2017,130(12):1409-1417.
[17] Cheson BD,Pfistner B,Juweid ME,et al.Revised response criteria for malignant lymphoma[J].J Clin Oncol,2007,25(5):579-586.
[18] Treon SP,Merlini G,Morra E,et al.Report from the Sixth International Workshop on Waldenstrom's Macroglobulinemia[J].Cl Lymph Myelom Leuk,2011,11(1):68-73.
[19] Mulligan SP,Karlsson K,Stromberg M,et al.Cladribine prolongs progression-free survival and time to second treatment compared to fludarabine and high-dose chlorambucil in chronic lymphocytic leukemia[J].Leuk Lymphoma,2014,55(12):2769-2777.
[20] Troch M,Kiesewetter B,Willenbacher W,et al.Rituximab plus subcutaneous cladribine in patients with extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue:a phase II study by the Arbeitsgemeinschaft Medikamentose Tumortherapie[J].Haematologica,2013,98(2):264-268.
[21] Inwards DJ,Fishkin PA,Hillman DW,et al.Long-term results of the treatment of patients with mantle cell lymphoma with cladribine(2-CDA)alone(95-80-53) or 2-CDA and rituximab(N0189) in the North Central Cancer Treatment Group[J].Cancer,2008,113(1):108-116.
[22] Puvvada SD,Guillen-Rodriguez J,Kumar A,et al.Phase 2 Open-Label Study of Bortezomib,Cladribine,and Rituximab in Advanced,Newly Diagnosed,and Relapsed/Refractory Mantle-Cell and Indolent Lymphomas[J].Clin Lymph Myelom Leuk,2018,18(1):58-64.
[23] Orciuolo E,Buda G,Sordi E,et al.2CdA chemotherapy and rituximab in the treatment of marginal zone lymphoma[J].Leukemia Res,2010,34(2):184-189.
[24] Spurgeon SE,Pindyck T,Okada C,et al.Cladribine plus rituximab is an effective therapy for newly diagnosed mantle cell lymphoma[J].Leuk Lymphoma,2011,52(8):1488-1494.
[25] Blum KA,Johnson JL,Niedzwiecki D,et al.Prolonged follow-up after initial therapy with 2-chlorodeoxyadenosine in patients with indolent non-Hodgkin lymphoma:results of Cancer and Leukemia Group B Study 9153[J].Cancer,2006,107(12):2817-2825.
[26] Kiesewetter B,Dolak W,Simonitsch-Klupp I,et al.Long-term safety and activity of cladribine in patients with extranodal B-cell marginal zone lymphoma of the mucosa-associated lymphoid tissue(MALT)lymphoma[J].Hematol Oncol,2017,35(2):177-186.
[27] Nagai H,Ogura M,Kusumoto S,et al.Cladribine combined with rituximab(R-2-CdA)therapy is an effective salvage therapy in relapsed or refractory indolent B-cell non-Hodgkin lymphoma[J].Eur J Haematol,2011,86(2):117-123.
[28] Rivas-Delgado A,Magnano L,Moreno-Velázquez M,et al.Response duration and survival shorten after each relapse in patients with follicular lymphoma treated in the rituximab era[J].Br J Haematol,2019,184(5):753-759.
[29] Kiesewetter B,Simonitsch-Klupp I,Dolak W,et al.Depth of remission following first-line treatment is an independent prognostic marker for progression-free survival in gastric mucosa-associated lymphoid tissue(MALT)lymphoma[J].Cancers,2020,12(2):492.
[30] Czuczman MS,Koryzna A,Mohr A,et al.Rituximab in combination with fludarabine chemotherapy in low-grade or follicular lymphoma[J].J Clin Oncol,2005,23(4):694-704.
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