TY - JOUR
T1 - Lenalidomide plus R-CHOP21 in elderly patients with untreated diffuse large B-cell lymphoma
T2 - Results of the REAL07 open-label, multicentre, phase 2 trial
AU - Vitolo, Umberto
AU - Chiappella, Annalisa
AU - Franceschetti, Silvia
AU - Carella, Angelo Michele
AU - Baldi, Ileana
AU - Inghirami, Giorgio
AU - Spina, Michele
AU - Pavone, Vincenzo
AU - Ladetto, Marco
AU - Liberati, Anna Marina
AU - Molinari, Anna Lia
AU - Zinzani, Pierluigi
AU - Salvi, Flavia
AU - Fattori, Pier Paolo
AU - Zaccaria, Alfonso
AU - Dreyling, Martin
AU - Botto, Barbara
AU - Castellino, Alessia
AU - Congiu, Angela
AU - Gaudiano, Marcello
AU - Zanni, Manuela
AU - Ciccone, Giovannino
AU - Gaidano, Gianluca
AU - Rossi, Giuseppe
N1 - Funding Information:
This study is sponsored by Fondazione Italiana Linfomi and was partly funded by Celgene. Lenalidomide was provided for free by Celgene. We thank Pasqualina De Masi, Sonia Perticone, and all the staff of the Fondazione Italiana Linformi for management of the study, and Ronald van Olffen (Excerpta Medica BV, Amsterdam, Netherlands) for medical writing services, which were funded by Celgene. GI is supported by the Italian Association for Cancer Research Special Program in Clinical Molecular Oncology ( 5x1000 10007 ).
Funding Information:
UV has been a paid speaker for Roche, Takeda, Celgene, and Pfizer; has participated in advisory boards for Celgene and Janssen-Cilag; and is a paid member of a Roche global advisory board. GI was paid by Celgene to speak at SAB Italy 2013. ML has been a paid speaker for Roche and Celgene. MD received grants from Celgene Germany during the conduct of this study; and grants and personal fees from Celgene and Roche. GG has been a paid speaker for Roche, Celgene, Onyx, Novartis, GlaxoSmithKline, Morphosys; and grants from Celgene. GR has been a paid speaker for Celgene Italy, outside the submitted work. The other authors declare no competing interests.
PY - 2014/6
Y1 - 2014/6
N2 - Background: 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.
AB - Background: 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.
UR - http://www.scopus.com/inward/record.url?scp=84901391325&partnerID=8YFLogxK
U2 - 10.1016/S1470-2045(14)70191-3
DO - 10.1016/S1470-2045(14)70191-3
M3 - Article
SN - 1470-2045
VL - 15
SP - 730
EP - 737
JO - The Lancet Oncology
JF - The Lancet Oncology
IS - 7
ER -