Derenzini Enrico, Cignetti Alessandro, Tabanelli Valentina, Gottardi Daniela, Gerbino Elvira, Vanazzi Anna, Sammassimo Simona, Maraglino Alessio Maria Edoardo, Melle Federica, Motta Giovanna, Malengo Daniela, Omodeo Salè Emanuela, Bonello Lisa, Pastano Rocco, Pileri Stefano, Carnevale Schianca Fabrizio, Tarella Corrado
Oncohematology Division, IEO European Institute of Oncology IRCCS, Via Ripamonti 435, 20141 Milan, Italy.
Department of Health Sciences, University of Milan, Via Antonio di Rudinì 8, 20142 Milan, Italy.
Hematol Rep. 2024 Dec 13;16(4):795-803. doi: 10.3390/hematolrep16040075.
Richter syndrome (RS) represents a major unmet need in the lymphoma field, being refractory to chemoimmunotherapy and targeted agents. The BCL-2 inhibitor venetoclax in combination with dose-adjusted EPOCH-R chemoimmunotherapy showed promising efficacy in patients affected by RS. However, responses were not durable, suggesting the need for further treatment optimization. Here, we report two cases of RS achieving long-term complete remission with intensified chemoimmunotherapy (Rituximab-G-MALL B-ALL/NHL2002 regimen) plus venetoclax induction, followed by haploidentical hematopoietic stem cell transplant (allo-HSCT). Venetoclax was given continuously for 14 consecutive days after every Rituximab-G-MALL cycle in off-label use. An accelerated venetoclax rump-up schedule was used in both patients to reach the maximal dose. Maximal venetoclax dose was 300 mg and 400 mg in patient 1 and patient 2, respectively. The combined treatment was well tolerated, with no major infective complications or non-hematological toxicities. In both patients, immunosuppression was discontinued within day 180 after transplant with no graft-versus-host-disease flares. Both patients are alive and in continuous complete remission after 60 and 72 months following allo-HSCT. This report supports the feasibility of a combination treatment with BCL-2 inhibitors and intensive chemoimmunotherapy as a bridge to allo-HSCT in RS.
里氏综合征（RS）是淋巴瘤领域一个尚未满足的重大需求，对化疗免疫疗法和靶向药物均具有耐药性。BCL-2抑制剂维奈克拉联合剂量调整的EPOCH-R化疗免疫疗法在RS患者中显示出有前景的疗效。然而，缓解并不持久，这表明需要进一步优化治疗。在此，我们报告两例RS患者通过强化化疗免疫疗法（利妥昔单抗-G-MALL B-ALL/NHL2002方案）加维奈克拉诱导治疗，随后进行单倍体造血干细胞移植（allo-HSCT），实现了长期完全缓解。维奈克拉在每个利妥昔单抗-G-MALL周期后连续使用14天，属于超适应症用药。两名患者均采用加速的维奈克拉递增方案以达到最大剂量。患者1和患者2的维奈克拉最大剂量分别为300 mg和400 mg。联合治疗耐受性良好，未出现重大感染并发症或非血液学毒性。两名患者在移植后180天内均停用免疫抑制剂，未出现移植物抗宿主病复发。两名患者在allo-HSCT后60个月和72个月时均存活且持续完全缓解。本报告支持了在RS中使用BCL-2抑制剂与强化化疗免疫疗法联合治疗作为allo-HSCT桥梁的可行性。
