Expert Point of View: Leslie Popplewell, MD
“Naratuximab emtansine plus rituximab appears to be an effective and well tolerated combination in a heavily pretreated population. The results of the study are very promising,” said Leslie Popplewell, MD, Associate Clinical Professor, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, California.
She noted that the response rate to this combination is similar to that observed with another antibody-drug conjugate, polatuzumab vedotin, which is given in combination with bendamustine and rituximab. In the phase II ROMULUS study, the objective response rate with polatuzumab vedotin plus rituximab in patients with diffuse large B-cell lymphoma (DLBLC) was 54%, with complete responses seen in 21%.1 In a small study of polatuzumab vedotin plus bendamustine and rituximab, a complete response rate of 40% was noted.2 The regimen of polatuzumab vedotin/bendamustine/ritixumab is now listed as a second-line option for patients who are not eligible for transplantation in the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology.
Leslie Popplewell, MD
“We have been giving polatuzumab vedotin to some patients as a bridge to chimeric antigen receptor (CAR) T-cell therapy,” Dr. Popplewell said. Naratuximab emtansine plus rituximab could potentially be useful for this purpose as well, she predicted.
Dr. Popplewell is interested in seeing the effect of this combination therapy in patients who have received CAR T-cell therapy. “That’s an issue with some trials—excluding patients who have already had CAR T-cell therapy. It would be interesting to see how this drug performs in those patients, because, increasingly, the goal for patients with refractory disease is to try to get there.”
Dr. Popplewell suggested the next step with naratuximab emtansine is to study it in combination with bendamustine, gemcitabine, or other agents typically used in refractory DLBCL.
DISCLOSURE: Dr. Popplewell has received honoraria from Hoffmann–La Roche and Pfizer; and has been reimbursed for travel, accommodations, or other expenses by Novartis.
1. Morschhauser F, Flinn IW, Advani R, et al: Polatuzumab vedotin or pinatuzumab vedotin plus rituximab in patients with relapsed or refractory non-Hodgkin lymphoma: Final results from a phase 2 randomised study (ROMULUS). Lancet Haematol 6:e254-e265, 2019.
2. Sehn LH, Herrera AF, Flowers CR, et al: Polatuzumab vedotin in relapsed or refractory diffuse large B-cell lymphoma. J Clin Oncol 38:155-165, 2020.
The combination of the CD37-targeting antibody-drug conjugate naratuximab emtansine and rituximab yielded deep and long-lasting responses in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), in a phase II trial presented during the 2021 European Hematology Association...