Stathis Anastasios, Pirosa Maria Cristina, Orsucci Lorella, Feugier Pierre, Tani Monica, Ghesquières Hervé, Musuraca Gerardo, Rossi Francesca Gaia, Merli Francesco, Guièze Romain, Gyan Emmanuel, Gini Guido, Marino Dario, Gressin Remy, Morschhauser Franck, Cavallo Federica, Palombi Francesca, Conconi Annarita, Tessoulin Benoît, Tilly Hervé, Zanni Manuela, Cabras Maria Giuseppina, Capochiani Enrico, Califano Catello, Celli Melania, Pulsoni Alessandro, Angrilli Francesco, Occhini Ubaldo, Casasnovas René-Olivier, Cartron Guillaume, Devizzi Liliana, Haioun Corinne, Liberati Anna Marina, Houot Roch, Merli Michele, Pietrantuono Giuseppe, Re Francesca, Spina Michele, Landi Francesco, Cavalli Franco, Bertoni Francesco, Rossi Davide, Ielmini Nicoletta, Borgo Elena, Luminari Stefano, Zucca Emanuele, Thieblemont Catherine
Oncology Institute of Southern Switzerland, EOC, Bellinzona, Switzerland; Università della Svizzera Italiana, Faculty of Biomedical Sciences, Lugano.
Oncology Institute of Southern Switzerland, EOC, Bellinzona, Switzerland; Institute of Oncology Research, Bellinzona.
Haematologica. 2024 Aug 1;109(8):2564-2573. doi: 10.3324/haematol.2023.283918.
The IELSG38 trial was conducted to investigate the effects of subcutaneous (SC) rituximab on the complete remission (CR) rate and the benefits of SC rituximab maintenance in patients with extranodal marginal zone lymphoma (MZL) who received front-line treatment with chlorambucil plus rituximab. Study treatment was an induction phase with oral chlorambucil 6 mg/m2/day on weeks 1-6, 9-10, 13-14, 17-18, and 21-22, and intravenous rituximab 375 mg/m2 on day 1 of weeks 1-4, and 1,400 mg SC on weeks 9, 13, 17, and 21. Then, a maintenance phase followed with rituximab administered at 1,400 mg SC every two months for two years. Of the 112 patients enrolled, 109 were evaluated for efficacy. The CR rates increased from 52% at the end of the induction phase to 70% upon completion of the maintenance phase. With a median follow-up of 5.8 years, the 5-year event-free, progression-free, and overall survival rates were 87% (95% CI: 78-92), 84% (95% CI: 75-89), and 93% (95% CI: 86-96), respectively. The most common grade ≥3 toxicities were neutropenia (33%) and lymphocytopenia (16%). Six patients experienced treatment-related serious adverse events, including fever of unknown origin, sepsis, pneumonia, respiratory failure, severe cerebellar ataxia, and fatal acute myeloid leukemia. The trial showed that SC rituximab did not improve the CR rate at the conclusion of the induction phase, which was the main endpoint. Nevertheless, SC rituximab maintenance might have facilitated long-term disease control, potentially contributing to enhanced event-free and progression-free survival.
IELSG38试验旨在研究皮下注射利妥昔单抗对接受苯丁酸氮芥加利妥昔单抗一线治疗的结外边缘区淋巴瘤（MZL）患者完全缓解（CR）率的影响以及皮下注射利妥昔单抗维持治疗的益处。研究治疗包括诱导期，第1 - 6周、9 - 10周、13 - 14周、17 - 18周和21 - 22周口服苯丁酸氮芥6mg/m²/天，第1 - 4周第1天静脉注射利妥昔单抗375mg/m²，第9周、13周、17周和21周皮下注射1400mg。然后是维持期，每两个月皮下注射利妥昔单抗1400mg，持续两年。在纳入的112例患者中，109例接受了疗效评估。CR率从诱导期结束时的52%提高到维持期结束时的70%。中位随访5.8年，5年无事件生存率、无进展生存率和总生存率分别为87%（95%CI：78 - 92）、84%（95%CI：75 - 89）和93%（95%CI：86 - 96）。最常见的≥3级毒性是中性粒细胞减少（33%）和淋巴细胞减少（16%）。6例患者发生了与治疗相关的严重不良事件，包括不明原因发热、败血症、肺炎、呼吸衰竭、严重小脑共济失调和致命性急性髓系白血病。该试验表明，皮下注射利妥昔单抗在诱导期结束时未提高CR率，而诱导期结束时的CR率是主要终点。尽管如此，皮下注射利妥昔单抗维持治疗可能有助于长期疾病控制，可能有助于提高无事件生存率和无进展生存率。
