Lenalidomide plus R-CHOP21 in elderly patients with untreated diffuse large B-cell lymphoma: results of the REAL07 open-label, multicentre, phase 2 trial

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• 作者：Dr Umberto Vitolo ; MD^a ; ^{uvitolo@cittadellasalute.to.it" class="auth_mail} ; Annalisa Chiappella ; MD^a ; Silvia Franceschetti ; MD^b ; Angelo Michele Carella ; MD^c ; Ileana Baldi ; PhD^d ; Prof Giorgio Inghirami ; MD^e ; ^g ; Michele Spina ; MD^h ; Vincenzo Pavone ; MDⁱ ; Marco Ladetto ; MD^f ; Prof Anna Marina Liberati ; MD^j ; Anna Lia Molinari ; MD^k ; Prof Pierluigi Zinzani ; MD^l ; Flavia Salvi ; MD^m ; Pier Paolo Fattori ; MDⁿ ; Alfonso Zaccaria ; MD^o ; Prof Martin Dreyling ; MD^p ; Barbara Botto ; MD^a ; Alessia Castellino ; MD^a ; Angela Congiu ; MD^c ; Marcello Gaudiano ; PhD^e ; ^g ; Manuela Zanni ; MD^f ; Giovannino Ciccone ; MD^q ; Prof Gianluca Gaidano ; MD^b ; Giuseppe Rossi ; MD^r ; on behalf of the Fondazione Italiana Linfomi
• 刊名：Lancet Oncology
• 出版年：June 2014
• 年：2014
• 卷：15
• 期：7
• 页码：730-737
• 全文大小：497 K

文摘

Up to 40% of elderly patients with untreated diffuse large B-cell lymphoma (DLBCL) given a regimen of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone every 21 days (R-CHOP21) relapse or develop refractory disease. Lenalidomide has high activity in relapsed or refractory aggressive B-cell lymphomas. In phase 2 of the REAL07 trial, we aimed to establish the safety and efficacy of the combination of lenalidomide and R-CHOP21 in elderly patients with untreated DLBCL.

Methods

REAL07 was an open-label, multicentre trial that was done in 13 centres in Italy and one in Germany. Eligible patients were aged 60–80 years; had newly diagnosed, untreated, CD20-positive, Ann Arbor stage II–IV DLBCL or grade 3b follicular lymphoma; had an Eastern Cooperative Oncology Group performance status of 0–2; had an International Prognostic Index (IPI) risk of low-intermediate, intermediate-high, or high; and were fit according to comprehensive geriatric assessment. Participants were to receive 15 mg oral lenalidomide on days 1–14 of six 21-day cycles, and standard doses of R-CHOP21 chemotherapy (375 mg/m² intravenous rituximab, 750 mg/m² intravenous cyclophosphamide, 50 mg/m² intravenous doxorubicin, and 1·4 mg/m² intravenous vincristine on day 1, and 40 mg/m² oral prednisone on days 1–5). The primary endpoint was frequency of overall response (complete response [CR] and partial response [PR]), which was assessed by ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) PET at the end of the treatment. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00907348.

Findings

49 patients were included in phase 2: nine had been enrolled into phase 1 between Oct 23, 2008, and June 4, 2009, and had received the maximum tolerated dose of 15 mg lenalidomide; and 40 were enrolled into phase 2 between April 28, 2010, and June 3, 2011. 45 patients (92%, 95% CI 81–97) achieved a response (42 [86%] CR; three [6%] PR). Three patients (6%) did not respond and one (2%) died for reasons unrelated to treatment or disease. 277 (94%) of 294 planned cycles of lenalidomide and R-CHOP21 were completed. Grade 3–4 neutropenia was reported in 87 cycles (31%), grade 3–4 leukopenia in 77 (28%), and grade 3–4 thrombocytopenia in 35 (13%). No grade 4 non-haematological adverse events were reported. No patients died during the study as a result of toxic effects.

Interpretation

Lenalidomide with R-CHOP21 is effective and safe in elderly patients with untreated DLBCL.

Funding

Fondazione Italiana Linfomi and Celgene.