Lenalidomide Plus R-CHOP21 Highly Active in Elderly Patients With Untreated Diffuse Large B-Cell Lymphoma
Lenalidomide (Revlimid) is active in relapsed or refractory aggressive B-cell lymphomas. In a European phase II trial (REAL07) reported in The Lancet Oncology, Vitolo et al examined the addition of lenalidomide to rituximab (Rituxan), cyclophosphamide, doxorubicin, vincristine, and prednisolone every 21 days (R-CHOP21) in elderly patients with untreated diffuse large B-cell lymphoma. The regimen produced a high response rate and was safe in this population.
Study Details
In this open-label study, 49 patients aged 60 to 80 years with newly diagnosed untreated CD20-positive Ann Arbor stage II to IV diffuse large B-cell lymphoma or grade 3b follicular lymphoma at 1 German and 13 Italian centers received lenalidomide at 15 mg on days 1 to 14 of six 21-day cycles and standard-dose R-CHOP21 (rituximab at 375 mg/m2, cyclophosphamide at 750 mg/m2, doxorubicin at 50 mg/m2, and vincristine at 1.4 mg/m2 on day 1 and prednisone at 40 mg/m2 on days 1–5). Patients had to have Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 and International Prognostic Index (IPI) risk of low-intermediate, intermediate-high, or high and had to be fit according to comprehensive geriatric assessment. The primary endpoint was overall response assessed by 18F-fluorodeoxyglucose positron-emission tomography (PET).
Of the 49 patients, 9 had participated in a phase I trial between October 2008 and June 2009 and had received the maximum tolerated lenalidomide dose of 15 mg and the remainder were enrolled between April 2010 and June 2011. Patents had a median age of 69 years (range = 64–71 years); 59% were male; 86% had ECOG performance status of 0 or 1; and IPI risk was low-intermediate in 39% and high-intermediate or high in 61%. Ninety-two percent of patients had diffuse large B-cell lymphoma, 8% had follicular lymphoma grade 3b, 35% had bone marrow involvement, 43% had B symptoms, 45% had elevated lactate dehydrogenase, and 69% had elevated β2-microglobulin.
High Response Rate
Overall, response was observed in 45 patients (92%, 95% confidence interval = 81%–97%), including complete response in 42 (86%). Three patients (6%) did not respond, and one (2%) died from causes unrelated to treatment or disease. The three patients with partial response received additional involved-field radiotherapy to sites of residual uptake on PET-computed tomography and subsequently achieved complete response. After a median follow-up of 28 months, 2-year overall survival was 92%, progression-free survival was 80%, and event-free survival was 70%.
Toxicity
Of 294 planned cycles of lenalidomide and R-CHOP21, 277 (94%) were completed. Granulocyte colony-stimulating factor (Neupogen) was used in 235 (85%) of the 277 cycles.
Hematologic adverse events included grade 3 and grade 4 neutropenia in 14% and 15%, leukopenia in 22% and 37%, thrombocytopenia in 12% and 18%, and anemia in 18% and 2%; grade 3 febrile neutropenia occurred in 10%. The most common nonhematologic adverse events of any grade were neurologic events (44%) and constipation (20%). The most common grade 3 adverse events were neurologic events (4%) and deep-vein thrombosis (4%); no grade 4 events were observed.
No deaths in the study were related to drug toxicity. One patient was diagnosed with intraductal prostatic cancer after 12 months off treatment and one with bladder urothelial carcinoma after 6 months off treatment.
The investigators concluded, “[O]ur data, although from a small cohort of patients, suggest that lenalidomide plus R-CHOP21 could be an effective and safe new treatment modality for elderly patients with untreated [diffuse large B-cell lymphoma]. Our encouraging data warrant a future phase 3 randomised trial comparing lenalidomide plus R-CHOP21 with R-CHOP21 alone in patients with untreated [diffuse large B-cell lymphoma].”
Umberto Vitolo, MD, of Azienda Ospedaliera Città della Salute e della Scienza di Torino, is the corresponding author for The Lancet Oncology article.
The study was supported by Fondazione Italiana Linfomi and Celgene. For full disclosures of the study authors, visit www.thelancet.com.
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