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

In patients with diffuse large B-cell lymphoma (DLBCL), concurrent deregulation of MYC and BCL2 confers inferior outcomes following R-CHOP. Dose-adjusted EPOCH-R (DA-EPOCH-R) produces favorable results in patients with dual MYC and BCL2 rearrangement (double-hit lymphoma, DHL), but there is 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 (23 DHL and 32 DEL) were enrolled and treated. Patients had median age of 65 years (range, 25-82), IPI ≥ 3 in 69% (38/55), and stage III/IV in 91% (50/55). The overall response rate was 90.9% with complete response rate of 83.6%. With median follow-up of 3.4 years, the primary endpoint efficacy criterion was met with 1-year and 2-year progression-free survival (PFS) 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 in patients with DHL and DEL. This trial was registered at www.clinicaltrials.gov (NCT02213913).