Combination of ofatumumab and reduced-dose CHOP for diffuse large B-cell lymphomas in patients aged 80 years or older: an open-label, multicentre, single-arm, phase 2 trial from the LYSA group

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• 作者：Prof Fré ; dé ; ric Peyrade ; MD^a ; ^{frederic.peyrade@nice.unicancer.fr} ; Serge Bologna ; MD^b ; Vincent Delwail ; MD^c ; Prof Jean Franç ; ois Emile ; MD^d ; Laurent Pascal ; MD^e ; Christophe Fermé ; MD^f ; Jean-Marc Schiano ; MD^g ; Prof Bertrand Coiffier ; MD^h ; Bernadette Corront ; MDⁱ ; Hassan Farhat ; MD^j ; Christophe Fruchart ; MD^k ; Prof Herve Ghesquieres ; MD^l ; Margaret Macro ; MD^m ; Prof Hervé ; Tilly ; MDⁿ ; Bachra Choufi ; MD^o ; Richard Delarue ; MD^p ; Olivier Fitoussi ; MD^q ; Jean Gabarre ; MD^r ; Prof Corinne Haioun ; MD^s ; Prof Fabrice Jardin ; MDⁿ
• 刊名：The Lancet Haematology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：4
• 期：1
• 页码：e46-e55
• 全文大小：543 K
• 卷排序：4

文摘

In 2011 we reported a rituximab plus miniCHOP (reduced-dose cyclophosphamide, doxorubicin, vincristine, and prednisone) combination for patients older than 80 years with diffuse large B-cell lymphoma (DLBCL). The 2-year overall survival was 59% (95% CI 49–67) with an excess of early toxicity. To improve those results we tested the same chemotherapy protocol in combination with ofatumumab and a pre-phase treatment.MethodsFor this open-label, multicentre, single-group, phase 2 trial, we recruited patients older than 80 years with untreated histologically-proven CD20-positive DLBCL, Ann Arbor stage I to IV, from 41 academic and hospital centres in France and Belgium. Patients received a pre-phase with oral vincristine (1 mg total dose 1 week before cycle 1 [day −7]) and oral prednisone (60 mg total dose starting 1 week before cycle 1, for 4 days [day −7 to day −4]) before the first cycle of the ofatumumab plus miniCHOP regimen. The regimen consisted of 1000 mg total dose of intravenous ofatumumab, 25 mg/m2 of intravenous doxorubicin, 400 mg/m2 of intravenous cyclophosphamide, and 1 mg of intravenous vincristine, on day 1 of each cycle; and 40 mg/m2 of oral prednisone on days 1–5. Ofatumumab was administered with 1000 mg of paracetamol and 50 mg of diphenhydramine. The primary endpoint was overall survival in the intention-to-treat population. The statistical analysis has been done on an intention-to-treat principle. This study was registered with ClinicalTrials.gov, number NCT01195714.FindingsBetween June 2, 2010, and Nov 4, 2011, we enrolled 120 patients. Age-adjusted International Prognostic Index was 2–3 in 68 (57%) of them. The median follow-up time was 26·8 months (IQR 24·5–30·1). The 2-year overall survival was 64·7% (95% CI 55·3–72·7) and median overall survival was not reached (95% CI 30·2–not reached). 45 patients died during the treatment, of whom 28 (62%) died due to lymphoma. The most common side-effect was haematological toxicity. Among the 120 patients, grade 3–4 neutropenia was reported in 24 (21%) patients and thrombocytopenia in two (2%), during the treatment period. Grade 3–4 anaemia was reported in six (5%) patients; seven (6%) patients had one episode of febrile neutropenia. 17 (15%) of 115 patients in the modified intention-to-treat population had red blood cell transfusions and three (3%) had platelet transfusions.InterpretationOur result suggest that, in patients older than 80 years with DLBCL, ofatumumab and pre-phase treatment seem to improve overall survival compared with the previously reported data. The combination of pre-phase treatment, a monoclonal antibody against CD20, and miniCHOP can be considered a new treatment platform for use in randomised clinical trial design for DLBCL treatment in patients older than 80 years.FundingThe Lymphoma Study Association, GlaxoSmithKline.