Up to 40% of elderly patients with untreated diffuse large B-cell lymphoma ( DLBCL ) given a regimen of Rituximab ( MabThera, Rituxan ), Cyclophosphamide ( Endoxan ), Doxorubicin ( Adriamycin ), Vincristine ( Oncovin ), and Prednisolone every 21 days ( R-CHOP21 ) relapse or develop refractory disease.
Lenalidomide ( Revlimid ) has high activity in relapsed or refractory aggressive B-cell lymphomas.
In phase 2 of the REAL07 trial, the aim of the study was to establish the safety and efficacy of the combination of Lenalidomide and R-CHOP21 in elderly patients with untreated diffuse large B-cell lymphoma.
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 diffuse large B-cell lymphoma 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.
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 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.
In conclusion, Lenalidomide with R-CHOP21 is effective and safe in elderly patients with untreated diffuse large B-cell lymphoma. ( Xagena )
Vitolo U et al, The Lancet Oncology 2014; 15: 730-737