Dr Shah on Unmet Needs in the Treatment of Older Patients with DLBCL

Nirav N. Shah, MD, associate professor, Froedtert & Medical College of Wisconsin, discusses the rationale for launching a phase 2 trial (NCT03943901) of split-dose R-CHOP (rituximab [Rituxan], cyclophosphamide, doxorubicin, vincristine, and prednisone) in older patients with diffuse large B-cell lymphoma (DLBCL), touching on the unmet needs seen in the treatment of this population.

DLBCL literature has shown variability in the ways that patients with older patients with DLBCL are treated, Shah begins. For example, some patients receive non–curative-intent options, some receive full doses of R-CHOP, and others receive R-miniCHOP, Shah explains. Notably, R-miniCHOP consists of an approximately 50% reduction of the R-CHOP regimen dose, he adds.

Based on these treatment inconsistencies in older patients with DLBCL, the phase 2 trial investigators aimed to find a way to deliver a tolerable dose of standard-of-care R-CHOP-21, which is evolving alongside the continued addition of new drugs to the treatment landscape, to older patients with comorbid conditions, Shah says. These patients are often unable to continually tolerate R-CHOP-21 when they receive it at the full dose intensity every 3 weeks, he expands. Therefore, the trial investigators aimed to fractionate the standard R-CHOP regimen into a split-dose regimen, Shah emphasizes.

In the trial, patients received CHOP at a 50% dose reduction on days 1 and 15 of a 28-day cycle plus a full dose of rituximab (Rituxan) on day 1 for up to 6 cycles, Shah continues. Most patients in the trial received 4 months of split-dose R-CHOP, and 5 patients with MRD-negative disease and an interim positron emission tomography/computed tomography Deauville score of 1 to 3 received 2 additional months of therapy. Thecumulative dose intensity of split-dose R-CHOP-21 that these older patients received was equivalent to the cumulative dose intensity of R-CHOP-21 that younger patients receive, he emphasizes. By fractionating R-CHOP-21 and delivering it over a longer-than-standard period in combination with growth factor support, the investigators feel that they have made R-CHOP-21 more tolerable for older patients with DLBCL, Shah concludes.