Dr Hill on the Use of Carfilzomib With R-CHOP in DLBCL

Brian T. Hill, MD, PhD, director, Lymphoid Malignancies Program, staff physician, the Cleveland Clinic Taussig Cancer Institute, discusses the final results from a phase 1/2 trial (NCT02073097) of carfilzomib (Kyprolis) given with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in the frontline setting for patients with non-germinal center diffuse large B-cell lymphoma (DLBCL).

Treatment outcomes for patients newly diagnosed with DLBCL are generally positive, though room for improvement remains, Hill begins. Over the years, researchers have sought additional agents to enhance the standard R-CHOP chemotherapy regimen. DLBCL is recognized as a heterogeneous entity with multiple subtypes, including the germinal center and activated B-cell subtypes, which can be further subclassified, he explains. Earlier studies indicated the potential benefit of incorporating a proteasome inhibitor (PI), specifically bortezomib (Velcade), alongside R-CHOP, Hill notes.

Although randomized phase 3 trials comparing R-CHOP with bortezomib plus R-CHOP were ongoing, investigators initiated a study investigating the second-generation PI carfilzomib in combination with R-CHOP, he expands. Unlike bortezomib, carfilzomib is administered intravenously and does not cause peripheral neuropathy, which is a potentially dose-limiting adverse effect, especially when agents are combined with vincristine-containing chemotherapy, he elucidates. This phase 1/2 trial involved a meticulous phase 1 dose escalation portion to identify the recommended phase 2 dose, Hill states. Subsequently, 48 patients were enrolled, and 47 patients were treated with the combination of R-CHOP and carfilzomib. The phase 2 expansion portion of the study included patients with the non–germinal center subtype of DLBCL. The findings indicated that the combination was both safe and effective in this population, he adds.

As part of safety monitoring, echocardiograms were conducted at baseline and the conclusion of therapy to assess excess cardiac risk, Hill continues. Notably, no significant changes in ejection fraction were observed, relative to the changes seen in control patients who underwent echocardiograms after R-CHOP therapy, he explains. This research sheds light on the potential benefits of incorporating carfilzomib into DLBCL treatment regimens, offering a promising avenue for further exploration and optimization of therapeutic strategies, Hill concludes.