Combining Everolimus With R-CHOP in Diffuse Large B-Cell Lymphoma

It may be possible to improve outcomes in patients with B-cell lymphoma. The targeted therapy drug everolimus may be safely combined with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in newly diagnosed, untreated diffuse large B-cell lymphoma (DLBCL) and potentially improve outcomes, according to a pilot study published in The Lancet Haematology.  

Everolimus combined with R-CHOP was found to be well-tolerated by patients with no dose-limiting toxicity reached within the planned dose escalation. The study demonstrated that 96% achieved an overall response, and all responders achieved a complete metabolic response to the treatment. The findings indicate that drugs targeting the P13K-mTOR pathway may provide an added benefit when combined with standard R-CHOP therapy.

“There is an unmet need to develop new therapies based on R-CHOP to try to increase the cure rate for diffuse large B-cell lymphoma,” said lead study author Patrick Johnston, MD, Ph.D, who is a hematologist at Mayo Clinic, Rochester, Minn., in a news release. “This pilot study suggests that adding mTOR inhibitors to standard therapy could improve outcomes, though it needs to be validated in a larger clinical trial.”

Diffuse large B-cell lymphoma is the most common type of non-Hodgkin lymphoma and the standard accepted treatment for DLBCL is a combination R-CHOP delivered in a 21-day cycle for 6 cycles. However, this regimen typically cures only approximately 60% of patients, according to the study authors.

Dr. Johnston and his colleagues scoured the scientific literature in search of ways to improve the cure rate and found that numerous studies have demonstrated the importance of the mTOR pathway in the pathogenesis of DLBCL cells in the laboratory. In addition, clinical studies have documented the single-agent efficacy of everolimus in relapsed DLBCL.

The researchers at the Mayo Clinic conducted a phase I feasibility study in 24 patients with new, previously untreated DLBCL. Patients received everolimus for 14 days in combination with R-CHOP-21. No relapses with DLBCL occurred and all patients achieved the predictive milestone of being event-free at 12 months from enrollment. The treatment was well-tolerated, and the most common adverse events were hematological in nature, such as grade 4 neutropenia (75%) and grade 3 febrile neutropenia (21%).

In this study, the researchers tested two schedules. The first one was everolimus given in the fasting state on days 1–10 of the R-CHOP cycle. The second schedule was everolimus give days 1–14 of the R-CHOP cycle. The patients were treated between March 21, 2012, and Sept 15, 2014, and the median follow-up was 21.5 months.

Dr. Johnston said the encouraging outcome results and toxicity profile of this new regimen, along with the worldwide availability of everolimus, make it potentially applicable to the large population of DLBCL patients.