Krish Patel, MD, Talks Glofitamab, Other Novel Therapies in DLBCL

Dr. Patel, of the Swedish Cancer Institute in Seattle, Washington, discussed novel therapies in the lymphoma space, including the bispecific antibody glofitamab in this episode of “The HemOnc Pulse.”

Dr. Patel shared data from the POLARIX trial, which compared polatuzumab plus R-CHP with R-CHOP in patients with diffuse large B-cell lymphoma (DLBCL). He also noted that chimeric antigen receptor (CAR) T-cell therapy has become a preferred option for early relapse in transplant-eligible patients.

The podcast then shifted gears into bispecific antibodies, which Dr. Patel described as antibodies that work by targeting a tumor antigen. The bispecific antibodies currently approved and available to use in lymphoma are CD3 and C20.

The conversation turned to glofitamab, which was highlighted in abstracts at the 65th American Society of Hematology Annual Meeting & Exposition.

“Glofitamab is approved under accelerated basis based on a phase II cohort of the original phase I trial of glofitamab,” Dr. Patel explained. “That specific expansion cohort looked at patients with relapsed or refractory diffuse large B-cell lymphoma that had two prior lines of therapy. The study design was to give the patients a fixed duration of glofitamab.”

The trial administered glofitamab in step-up dosing (small dose, medium dose, and then full dose), then every three weeks for up to 12 cycles. The complete response rate was 40%.

On the topic of the study’s design, Dr. Patel further discussed fixed-duration therapy.

“It’s important in large cell lymphoma that we continue to develop fixed-duration treatment regimens and figure out how we can shorten the time frame to give these therapies,” he said.

“In my view, [glofitamab] is a very effective therapy for a subset of patients,” he continued. “What’s exciting about it is bispecific antibodies potentially can be combined with other therapies. The field is moving forward with looking at those combinations while we have this approval for single agent glofitamab in third-line DLBCL and beyond.”

Approximately one-third of the patients enrolled in the study had prior CAR-T cell therapy. Bispecific antibodies are the go-to therapy for patients who have had CAR T-cell therapy and have not achieved a cure, according to Dr. Patel.

“Having something that could cure patients after failing CAR-T is huge,” Chadi Nabhan, MD, MBA, FACP, the host of “The HemOnc Pulse” said.

The toxicity profile is similar to that of CAR-T, Dr. Patel noted, such as cytokine release syndrome (CRS) and neurologic toxicities. However, lower grade CRS is observed with bispecific antibodies due to step-up dosing.

Finally, Drs. Nabhan and Patel discussed how to sequence therapy.

“There are trials of bispecific antibodies in the second-line setting to try to augment what we get with chemotherapy-based approaches. I think the story is still being told, and it’s very likely if these trials are successful that we’ll see them potentially as early as frontline therapy,” Dr. Patel said.