Survival Markedly Improved in Diffuse Large B-Cell Lymphoma with Everolimus, R-CHOP Combo Therapy

Survival Markedly Improved in Diffuse Large B-Cell Lymphoma with Everolimus, R-CHOP Combo Therapy

Combining everolimus, an inhibitor of the PI3K-mTOR pathway, with the standard R-CHOP therapy may greatly increase the cure rate of diffuse large B-cell lymphoma (DLBCL) patients who have not been previously treated. R-CHOP is a combination of drugs used to treat patients with lymphoma, and includes rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone.

The pilot Phase 1 study, developed by researchers at the Mayo Clinic, was published in The Lancet Hematology and titled “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.

“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,” Patrick Johnston, MD, PhD, a hematologist at Mayo Clinic and the study’s lead author, said in a press 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.”

The standard accepted treatment for DLBCL is an R-CHOP combination delivered in a 21-day cycle for six cycles, but this regimen only cures approximately 60 percent of patients.

The research team went through the literature to identify new therapies that could help improve the cure rate for DLBCL in combination with the R-CHOP-21 treatment. They decided to use an mTOR inhibitor (everolimus) because the PI3K-mTOR pathway was essential in non-Hodgkin’s lymphoma cells and, consistently, clinical studies had reported everolimus efficacy in relapsed DLBCL.

The pilot Phase 1 trial examined 24 patients with new, untreated DLBCL who received everolimus for 14 days in combination with R-CHOP-21 therapy. The results revealed that the combined therapy induced a 96 percent overall response rate (23 out of 24 patients), with all of the responders reaching a complete metabolic response, as assessed by positron emission tomography (PET) scans. The remaining patient later achieved a complete response with R-CHOP alone.

Importantly, all patients met a 12-month event-free survival, and none died in the 21.5 month median follow-up. No relapses with DLBCL occurred. The treatment was well-tolerated by patients with no dose limiting toxicity, with the most common side effects being reduced numbers of neutrophils, a type of immune cells.

“This study is the first to integrate a PI3K-mTOR agent with standard R-CHOP,” 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.”

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