Sequential treatment with rituximab followed by CHOP chemotherapy in adult B-cell post-transplant lymphoproliferative disorder (PTLD): the prospective international multicentre phase 2 PTLD-1 trial

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• 作者：Dr Ralf Trappe ; MD^a ; ^b ; ^{ralf.trappe@uksh.de} ; Stephan Oertel ; MD^c ; Prof Veronique Leblond ; MD^d ; Peter Mollee ; MBBS^e ; Monica Sender ; MD^f ; Prof Petra Reinke ; MD^g ; Ruth Neuhaus ; MD^h ; Hans Lehmkuhl ; MDⁱ ; Prof Heinz August Horst ; MD^b ; Prof Gilles Salles ; MD^j ; Franck Morschhauser ; MD^k ; Prof Arnaud Jaccard ; MD^l ; Prof Thierry Lamy ; MD^m ; Malte Leithä ; user ; MDⁿ ; Heiner Zimmermann ; MB BChir^b ; Prof Ioannis Anagnostopoulos ; MD^o ; Prof Martine Raphael ; MD^p ; Prof Hanno Riess ; MD^a ; Sylvain Choquet ; MD^d ; for the German PTLD Study Group ; the European PTLD Network
• 刊名：Lancet Oncology
• 出版年：2012
• 出版时间：February 2012
• 年：2012
• 卷：13
• 期：2
• 页码：196-206
• 全文大小：191 K

文摘

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Summary

Background

Post-transplantation lymphoproliferative disorder (PTLD) develops in 1-10 % of transplant recipients and can be Epstein-Barr virus (EBV) associated. To improve long-term efficacy after rituximab monotherapy and to avoid the toxic effects of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy seen in first-line treatment, we initiated a phase 2 trial to test whether the subsequent use of rituximab and CHOP would improve the outcome of patients with PTLD.

Methods

In this international multicentre open-label phase 2 trial, treatment-naive adult solid-organ transplant recipients diagnosed with CD20-positive PTLD who had failed to respond to upfront immunosuppression reduction received four courses of rituximab (375 mg/m² intravenously) once a week followed by 4 weeks without treatment and four cycles of CHOP every 3 weeks. In case of disease progression during rituximab monotherapy, CHOP was started immediately. Supportive therapy with granulocyte-colony stimulating factor after chemotherapy was mandatory and antibiotic prophylaxis was recommended. The primary endpoint was treatment efficacy measured as response rates in all patients who completed treatment with rituximab and CHOP, per protocol, and response duration, in all patients who completed all planned therapy and responded. Secondary endpoints were frequency of infections, treatment-related mortality, and overall survival. This study is registered at , number .

Findings

74 patients were enrolled between Dec 12, 2002 and May 5, 2008, of whom 70 patients were eligible to receive treatment. PTLD was of late type in 53 (76 % ) of 70 patients, monomorphic in 67 (96 % ) of 70, and histologically EBV associated in 29 (44 % ) of 66 cases. Four of 70 patients did not receive CHOP. 53 of 59 patients had a complete or partial response (90 % , 95 % CI 79-96), of which 40 (68 % , 55-78) were complete responses. At data cutoff (June 1, 2011) median response duration in the 53 patients who had responded to treatment had not yet been reached (>79¡¤1 months). The main adverse events were grade 3-4 leucopenia in 42 of 62 patients (68 % , 55-78) and infections of grade 3-4 in 26 of 64 patients (41 % , 29-53). Seven of 66 patients (11 % , 5-21) had CHOP-associated treatment-related mortality. Median overall survival was 6¡¤6 years (95 % CI 2¡¤8-10¡¤4; n=70).

Interpretation

Our results support the use of sequential immunochemotherapy with rituximab and CHOP in PTLD.

Funding

F Hoffmann-La Roche, Amgen Germany, Chuga? France.