Dr Shah on the Investigation of Split-Dose R-CHOP in DLBCL

Nirav N. Shah, MD, associate professor, Froedtert & Medical College of Wisconsin, discusses primary outcomes from a phase 2 trial (NCT03943901) investigating split-dose R-CHOP (rituximab [Rituxan], cyclophosphamide, doxorubicin, vincristine, and prednisone) in older patients with diffuse large B-cell lymphoma (DLBCL).

Elderly, unfit, or frail patients with DLBCL often have decreased tolerance of chemotherapy regimens. As a result, they typically receive non-anthracycline–based therapies or reduced regimens, such as R-miniCHOP, which is an approximately 50% reduction of the standard R-CHOP-21 dose. An alternative regimen for these patients is split-dose R-CHOP, where patients receive CHOP at a 50% dose reduction on days 1 and 15 of each 28-day cycle plus a full dose of rituximab on day 1 of each cycle for 6 cycles.

This ongoing phase 2 trial is evaluating split-dose R-CHOP in patients with untreated de novo or transformed stage IIX to IV DLBCL. Patients are required to be at least 75 years of age or aged 70 to 74 years with an elevated cumulative illness rating scale for geriatrics score.

The primary end point of this trial was end-of-treatment complete response (CR) rate, an outcome that can be measured early, Shah says. Of the 14 patients evaluated in the prespecified interim analysis, 10 achieved end-of-treatment CR, and follow-up is ongoing. This 71% CR rate is comparable to that seen in younger patients who receive R-CHOP-21, Shah notes. Having met the feasibility end point, this trial is continuing to enroll patients, Shah explains.

The trial investigators also conducted an interim evaluation of patients who had received 2 cycles of split-dose R-CHOP. These patients were stratified by minimal residual disease (MRD) negativity status using a cell-free DNA assay. Patients with MRD-negative disease and a Deauville score of 1 to 3 per positron emission tomography/computed tomography were offered an abbreviated regimen of split-dose R-CHOP. Among the 6 patients who met these criteria, 5 received the abbreviated regimen, and none had relapsed at the data cutoff date, Shah concludes.