CLL/SLL
建议的治疗方案(CSLL-D)
不伴缺失(17p)/TP53突变的CLL/SLL
一线治疗
●有严重合并症的体弱患者
(不能耐受嘌呤类似物治疗)
►奥比妥珠单抗 + 苯丁酸氮芥(1类推荐)
►依鲁替尼(1类推荐)
►奥法木单抗 + 苯丁酸氮芥
►利妥昔单抗+苯丁酸氮芥
►奥比妥珠单抗(2B类推荐)
►利妥昔单抗(3类推荐)
►苯丁酸氮芥(3类推荐)
●年龄 ≥65岁和小于65岁有明显合并症的患者
►奥比妥珠单抗 + 苯丁酸氮芥 (1类推荐)
►依鲁替尼(1类推荐)
►奥法木单抗 + 苯丁酸氮芥
►利妥昔单抗 + 苯丁酸氮芥
►苯达莫司汀 (如可耐受,第一疗程中的70mg/m2升至90 mg/m2)±利妥昔单抗
►奥比妥珠单抗(2B类推荐)
►苯丁酸氮芥(3类推荐)
►利妥昔单抗(3类推荐)
●年龄<65岁无明显合并症
►化学免疫治疗
◊FCRe(氟达拉滨,f环磷酰胺,利妥昔单抗)(1类推荐)
◊FRe(氟达拉滨,利妥昔单抗)
◊PCR (喷司他丁,环磷酰胺,利妥昔单抗)
◊苯达莫司±利妥昔单抗
►依鲁替尼
一线治疗后的维持治疗
●在一线治疗后,对于高风险患者 (MRD ≥10-2 或10-2>MRD≥10-4且IGHV未突变)考虑来那度胺维持治疗。
复发/难治性病例治疗
●有严重合并症的体弱患者或年龄≥65岁和小于65岁有明显合并症的患者
►依鲁替尼(1类推荐)
►Idelalisib + 利妥昔单抗(1类推荐)
►Idelalisibc
►Venetoclaxi,j ±利妥昔单抗
►化学免疫治疗
◊苯达莫司汀±利妥昔单抗
◊减量FCRe,f
◊减量PCR
◊大剂量甲泼尼龙(HDMP)+ 利妥昔单抗
◊利妥昔单抗+苯丁酸氮芥
◊依鲁替尼,苯达莫司汀, 利妥昔单抗 (3类推荐)
◊Idelalisib,苯达莫司汀,利妥昔单抗 (3类推荐)
►奥法木单抗
►阿托珠单抗(obinutuzumab)
►来那度胺±利妥昔单抗
►阿仑单抗±利妥昔单抗
►剂量密集的利妥昔单抗(2B类推荐)
●年龄<65岁无明显合并症
►依鲁替尼(1类推荐)
►Idelalisib + 利妥昔单抗(1类推荐)
►Idelalisib
►Venetoclax ± 利妥昔单抗
►化学免疫治疗
◊FCR
◊FC+奥法木单抗
◊PCR
◊苯达莫司汀±利妥昔单抗
◊RCHOP苯达莫司汀±利妥昔单抗
◊OFARe(奥沙利铂,氟达拉滨,阿糖胞苷,利妥昔单抗)
◊依鲁替尼,苯达莫司汀, 利妥昔单抗 (2B类推荐)
◊Idelalisib,c 苯达莫司汀,利妥昔单抗 (2B类推荐)
►奥法木单抗
►阿托珠单抗
►来那度胺±利妥昔单抗
►阿仑单抗±利妥昔单抗
►HDMP+ 利妥昔单抗
二线治疗后的维持治疗
(适用于复发或难治性病例治疗后完全或部分缓解)
●来那度胺维持治疗
●奥法木单抗维持治疗(2B类推荐)
伴缺失(17p)/TP53突变的的CLL/SLL
一线治疗
●依鲁替尼
●HDMP+利妥昔单抗
●阿托珠单抗+苯丁酸氮芥(3类推荐)
●阿仑单抗±利妥昔单抗
一线治疗后的维持治疗
●在一线治疗后,对于高风险患者 (MRD ≥10-2 或10-2>MRD≥10-4且IGHV未突变)考虑来那度胺维持治疗。
复发/难治性病例治疗
●依鲁替尼
●Venetoclax±利妥昔单抗
●Idelalisib+利妥昔单抗
●Idelalisib
●HDMP+利妥昔单抗
●来那度胺±利妥昔单抗
●阿仑单抗±利妥昔单抗
●奥法木单抗
●OFAR
二线治疗后的维持治疗
(适用于复发或难治性病例治疗后完全或部分缓解)
●来那度胺维持治疗
●奥法木单抗维持治疗(2B类推荐)
【参考文献】
阿仑单抗+利妥昔单抗
Faderl S, Ferrajoli A, Wierda W, et al. Alemtuzumab by continuous intravenous infusion followed by subcutaneous injection plus rituximab in the treatment of patients with chronic lymphocytic leukemia recurrence. Cancer 2010;116:2360-2365.
苯达莫司汀+ 利妥昔单抗
Knauf WU, Lissitchkov T, Aldaoud A, et al. Bendamustine compared with chlorambucil in previously untreated patients with chronic lymphocytic leukaemia: updated results of a randomized phase III trial. Br J Haematol 2012;159:67-77.
Fischer K, Cramer P, Busch R, et al. Bendamustine in combination with rituximab for previously untreated patients with chronic lymphocytic leukemia: A multicenter phase II trial of the German Chronic Lymphocytic Leukemia Study Group. J Clin Oncol 2012;30:3209-3216.
Eichhorst B, Fink AM, Bahlo J, et al. First-line chemoimmunotherapy with bendamustine and rituximab versus fludarabine, cyclophosphamide, and rituximab in patients with advanced chronic lymphocytic leukaemia (CLL10): an international, open-label, randomised, phase 3, non-inferiority trial. Lancet Oncol 2017;17:928-942.
Fischer K, Cramer P, Busch R et al. Bendamustine combined with rituximab in patients with relapsed and/or refractory chronic lymphocytic leukemia: A multicenter phase II trial of the German Chronic Lymphocytic Leukemia Study Group. J Clin Oncol 2011;29:3559-3566.
苯丁酸氮芥+利妥昔单抗
Hillmen P, Gribben JG, Follows GA, et al. Rituximab Plus Chlorambucil As First-Line Treatment for Chronic Lymphocytic Leukemia: Final Analysis of an Open-Label Phase II Study. J Clin Oncol 2014;32:1236-1241.
Foa R, Giudice ID, Cuneo A, et al. Chlorambucil plus rituximab with or without maintenance rituximab as first-line treatment for elderly chronic lymphocytic leukemia patients. Am J Hematol 2014;89:480-486.
FCR(氟达拉滨,环磷酰胺,利妥昔单抗)
Fischer K, Bahlo J, Fink AM, et al. Long-term remissions after FCR chemoimmunotherapy in previously untreated patients with CLL: updated results of the CLL8 trial. Blood 2017;127:208-215.
Eichhorst B, Fink AM, Bahlo J, et al. First-line chemoimmunotherapy with bendamustine and rituximab versus fludarabine, cyclophosphamide, and rituximab in patients with advanced chronic lymphocytic leukaemia (CLL10): an international, open-label, randomised, phase 3, non-inferiority trial. Lancet Oncol 2017;17:928-942.
Thompson PA, Tam CS, O’Brien SM, et al. Fludarabine, cyclophosphamide, and rituximab treatment achieves long-term disease-free survival in IGHV-mutated chronic lymphocytic leukemia. Blood 2015;127:303- 309.
Robak T, Dmoszynska A, Solal-Celigny P, et al. Rituximab plus fludarabine and cyclophosphamide prolongs progression-free survival compared with fludarabine and cyclophosphamide alone in previously treated chronic lymphocytic leukemia. J Clin Oncol 2010;28:1756-1765.
Badoux XC, Keating MJ, Wang X, et al. Fludarabine, cyclophosphamide, and rituximab chemoimmunotherapy is highly effective treatment for relapsed patients with CLL. Blood 2011;117:3016-3024.
FC(氟达拉滨,环磷酰胺)+ 奥法木单抗
Robak T, Warzocha K, Govind Babu K, et al. Ofatumumab plus fludarabine and cyclophosphamide in relapsed chronic lymphocytic leukemia: results from the COMPLEMENT 2 trial. Leuk Lymphoma 2017;58:1084-1093.
氟达拉滨+利妥昔单抗
Byrd JC, Peterson BL, Morrison VA, et al. Randomized phase 2 study of fludarabine with concurrent versus sequential treatment with rituximab in symptomatic, untreated patients with B-cell chronic lymphocytic leukemia: results from Cancer and Leukemia Group B 9712 (CALGB 9712). Blood 2003;101:6-14.
HDMP(高剂量甲基泼尼松龙)+利妥昔单抗
Bowen DA, Call TG, Jenkins GD, et al. Methylprednisolone-rituximab is an effective salvage therapy for patients with relapsed chronic lymphocytic leukemia including those with unfavorable cytogenetic features. Leukemia and Lymphoma 2007;48:2412-2417.
Castro JE, James DF, Sandoval-Sus JD, et al. Rituximab in combination with high-dose methylprednisolone for the treatment of chronic lymphocytic leukemia. Leukemia 2009;23:1779-1789.
Thornton PD, Matutes E, Bosanquet AG, et al. High dose methylprednisolone can induce remissions in CLL patients with p53 abnormalities. Ann Hematol 2003;82:759-765.
依鲁替尼,苯达莫司汀,利妥昔单抗
Chanan-Khan A, Cramer P, Demirkan F, et al. Ibrutinib combined with bendamustine and rituximab compared with placebo, bendamustine, and rituximab for previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma (HELIOS): a randomised, double-blind, phase 3 study. Lancet Oncol 2017;17:200-211.
Idelalisib, 苯达莫司汀,利妥昔单抗
Zelenetz AD, Brown JR, Delgado J, et al. Updated Analysis of Overall Survival in Randomized Phase III Study of Idelalisib in Combination with Bendamustine and Rituximab in Patients with Relapsed/Refractory CLL [abstract]. Blood 2017;128:Abstract 231.
OFAR(奥沙利铂,氟达拉滨,阿糖胞苷,利妥昔单抗)
Tsimberidou AM, Wierda WG,Plunkett W, et al. Phase I-II study of oxaliplatin, fludarabine, cytarabine, and rituximab combination therapy in patients with Richter's Syndrome or fludarabine-refractory chronic lymphocytic leukemia. J Clin Oncol 2008;26:196-203.
Tsimberidou AM, Wierda WG, Wen S, et al. Phase I-II clinical trial of oxaliplatin, fludarabine, cytarabine, and rituximab therapy in aggressive relapsed/refractory chronic lymphocytic leukemia or Richter syndrome. Clin Lymphoma Myeloma Leuk 2013;13:568-574.
PCR(喷司他丁,环磷酰胺,利妥昔单抗)
Lamanna N, Kalaycio M, Maslak P, et al. Pentostatin, cyclophosphamide, and rituximab is an active, well-tolerated regimen for patients with previously treated chronic lymphocytic leukemia. J Clin Oncol 2006;24:1575-1581.
Kay NE, Geyer SM, Call TG, et al. Combination chemoimmunotherapy with pentostatin, cyclophosphamide, and rituximab shows significant clinical activity with low accompanying toxicity in previously untreated B chronic lymphocytic leukemia. Blood 2007;109:405-411.
Venetoclax ±利妥昔单抗
Stilgenbauer S, Eichhorst B, Schetelig J, et al. Venetoclax in relapsed or refractory chronic lymphocytic leukaemia with 17p deletion: a multicentre, open-label, phase 2 study. Lancet Oncol 2016;17:768-778.
Jones J, Choi MY, Mato AR, et al. Venetoclax (VEN) Monotherapy for Patients with Chronic Lymphocytic Leukemia (CLL) Who Relapsed after or Were Refractory to Ibrutinib or Idelalisib [abstract]. Blood 2016;128:Abstract 637.
Seymour JF, Ma S, Brander DM, et al. Venetoclax plus rituximab in relapsed or refractory chronic lymphocytic leukaemia: a phase 1b study. Lancet Oncol 2017 (Epub Ahead of Print).
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