Adding Everolimus to R-CHOP Feasible for Diffuse Large B-cell Lymphoma
Everolimus administered for 14 days in combination with R-CHOP is feasible for the treatment of patients with 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%).
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"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."
- 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.