A multicenter phase 1/2 trial of lenalidomide and dose-adjusted EPOCH-R in MYC-associated DLBCL.

abstractIn patients with diffuse large B-cell lymphoma (DLBCL), concurrent deregulation of MYC and BCL2 confers inferior outcomes following R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). DA-EPOCH-R (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) produces favorable results in patients with dual MYC and BCL2 rearrangement (double-hit lymphoma [DHL]), but there are limited prospective data in both DHL and DLBCL with dual protein overexpression of Myc and Bcl2 (double-expressor lymphoma [DEL]). Lenalidomide (LEN) may enhance the response in MYC-driven lymphomas, prompting this investigator-initiated multicenter phase 1/2 study evaluating LEN with DA-EPOCH-R in adults with newly diagnosed DHL and DEL. Fifty-five patients (DHL, 23; DEL, 32) were enrolled and treated. Patients had a median age of 65 years (range, 25-82), International Prognostic Index ≥3 in 69% (38/55), and stage III/IV in 91% (50/55). The overall response rate was 90.9%, with a complete response rate of 83.6%. With a median follow-up of 3.4 years, the primary end point efficacy criterion was met with 1- and 2-year progression-free survival (PFS) rates of 85.5% and 78.2%, respectively. The 2-year overall survival was 83.6%. The most common adverse events (grade ≥3) were neutropenia (67%), anemia (67%), thrombocytopenia (49%), and neutropenic fever (35%). There were no grade 5 events. Second primary malignancy occurred in 6 patients (11%). LEN with DA-EPOCH-R for patients with DEL and DHL has a high response rate, encouraging survival, and met the primary PFS efficacy criterion. A randomized trial of DA-EPOCH-R with and without LEN would be needed to determine the specific benefit of LEN. This trial was registered at www.ClinicalTrials.gov as #NCT02213913.