Adding Everolimus to R-CHOP Feasible for Diffuse Large B-cell Lymphoma

Everolimus administered for 14 days in combination with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) is feasible for the treatment of patients with diffuse large B-cell lymphoma (DLBCL), a study published in The Lancet Haematology has shown.¹

The PI3K-mTORC pathway is upregulated in DLBCL and can be targeted with the mTOR complex 1 (mTORC1) inhibitor everolimus. Because everolimus has demonstrated activity in relapsed DLBCL, researchers explored the safety and efficacy of everolimus combined with standard treatment R-CHOP for 6 sets of 21-day cycles in a feasibility trial.

For the phase 1/feasibility study, investigators enrolled 24 patients with newly diagnosed, CD20-positive, stage II-IV DLBCL. All participants received everolimus 10 mg orally in combination with rituximab 375 mg/m² IV,  cyclophosphamide 750 mg/m² IV, doxorubicin 50 mg/m² IV, and vincristine 1.4 mg/m² (maximum 2.0 mg) IV all on day 1, and prednisone 100 mg/m² orally on days 1-5 of each 21-day cycle for 6 cycles.

Everolimus was evaluated at 2 different schedules: on days 1-10 or days 1-14 of each R-CHOP cycle. Patients also received pegfilgrastim 6 mg subcutaneously on day 2 of each cycle.

Results showed that at a median follow-up of 21.5 months, the overall response rate was 96% (95% CI, 79-100), and all patients who achieved a response also attained a complete metabolic response by PET. The remaining patient withdrew consent after cycle 1 and achieved a complete response with R-CHOP alone.

All 24 patients were event-free at 12 months and 9 patients, with sufficient follow-up data, were event-free at 24 months. Because no events occurred during the study or follow-up, investigators were unable to evaluate response duration or progression-free survival.

The most frequently reported grade 3 to 4 toxicities were hematologic; the most common were grade 4 neutropenia (75%) and grade 3 febrile neutropenia (21%).

“These findings suggest that drugs that target the PI3K-mTORC pathway add benefit when combined with standard R-CHOP,” the authors concluded. “The everolimus with R-CHOP regimen should be tested against standard R-CHOP alone in a randomized trial, to support the benefits of this novel combination noted in this study.”               

Reference

1. Johnston PB, LaPlant B, McPhail E, Habermann, TM, Inwards DJ, Micallef IN, et al. Everolimus combined with R-CHOP-21 for new, untreated, diffuse large B-cell lymphoma (NCCTG 1085 [Alliance]): safety and efficacy results of a phase 1 and feasibility trial [published online ahead of print June 5, 2016]. Lancet Haematol. doi: 10.1016/S2352-3026(16)30040-0.