UCLH Centre for Waldenström Macroglobulinaemia and Related Conditions, University College London Hospitals NHS Foundation Trust, London, UK.
Colorado Blood Cancer Institute, Sarah Cannon Research Institute, Denver, CO.
Semin Hematol. 2023 Mar;60(2):80-89. doi: 10.1053/j.seminhematol.2023.03.003. Epub 2023 Mar 27.
The consensus panel 2 (CP2) of the 11th International Workshop on Waldenström's macroglobulinemia (IWWM-11) has reviewed and incorporated current data to update the recommendations for treatment approaches in patients with relapsed or refractory WM (RRWM). The key recommendations from IWWM-11 CP2 include: (1) Chemoimmunotherapy (CIT) and/or a covalent Bruton tyrosine kinase (cBTKi) strategies are important options; their use should reflect the prior upfront strategy and are subject to their availability. (2) In selecting treatment, biological age, co-morbidities and fitness are important; nature of relapse, disease phenotype and WM-related complications, patient preferences and hematopoietic reserve are also critical factors while the composition of the BM disease and mutational status (MYD88, CXCR4, TP53) should also be noted. (3) The trigger for initiating treatment in RRWM should utilize knowledge of patients' prior disease characteristics to avoid unnecessary delays. (4) Risk factors for cBTKi related toxicities (cardiovascular dysfunction, bleeding risk and concurrent medication) should be addressed when choosing cBTKi. Mutational status (MYD88, CXCR4) may influence the cBTKi efficacy, and the role of TP53 disruptions requires further study) in the event of cBTKi failure dose intensity could be up titrated subject to toxicities. Options after BTKi failure include CIT with a non-cross-reactive regimen to one previously used CIT, addition of anti-CD20 antibody to BTKi, switching to a newer cBTKi or non-covalent BTKi, proteasome inhibitors, BCL-2 inhibitors, and new anti-CD20 combinations are additional options. Clinical trial participation should be encouraged for all patients with RRWM.
第 11 届华氏巨球蛋白血症国际研讨会（IWWM-11）的共识小组 2（CP2）审查并纳入了现有数据，以更新复发性或难治性 WM（RRWM）患者的治疗方法建议。IWWM-11CP2 的主要建议包括：（1）化疗免疫治疗（CIT）和/或共价布鲁顿酪氨酸激酶（cBTKi）策略是重要选择；它们的使用应反映先前的一线策略，并取决于它们的可用性。（2）在选择治疗方法时，生物年龄、合并症和健康状况很重要；复发的性质、疾病表型和与 WM 相关的并发症、患者的偏好和造血储备也是关键因素，而骨髓疾病的组成和突变状态（MYD88、CXCR4、TP53）也应注意。（3）RRWM 中启动治疗的触发因素应利用患者先前疾病特征的知识，避免不必要的延迟。（4）在选择 cBTKi 时，应解决与 cBTKi 相关毒性（心血管功能障碍、出血风险和同时用药）相关的风险因素。突变状态（MYD88、CXCR4）可能会影响 cBTKi 的疗效，TP53 破坏的作用需要进一步研究）在 cBTKi 失败的情况下，根据毒性情况，可以增加剂量强度。BTKi 失败后的选择包括用与之前使用的 CIT 无交叉反应的方案进行 CIT、在 BTKi 上加用抗 CD20 抗体、改用新的 cBTKi 或非共价 BTKi、蛋白酶体抑制剂、BCL-2 抑制剂和新的抗 CD20 组合是其他选择。应鼓励所有 RRWM 患者参加临床试验。
