Expert Point of View: Julio C. Chavez, MD

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Julio C. Chavez, MD, Associate Member in the Lymphoma Section of the Department of Malignant Hematology at Moffitt Cancer Center, Tampa, who co-moderated the session where the glofitamab study was presented, shared his thoughts with The ASCO Post.

“Glofitamab has great activity in high-risk relapsed/refractory diffuse large B-cell lymphoma as a single agent. This is an unmet need in the era of CAR [chimeric antigen receptor] T-cell therapy, since not all patients can be cured with CAR T. Secondly, unlike CAR T-cell therapy, it is an off-the-shelf treatment that allows patients to be treated as soon as it is clinically needed. Another attribute of this agent is that it is a time-limited option that allows patients to be off therapy if they achieve a complete response,” Dr. Chavez said.

“The study showed that the majority of patients who achieve a complete response do not relapse, which is pretty encouraging. It is also encouraging that retreatment with glofitamab is an option for patients who relapse; however, as with other agents in relapsed/refractory diffuse large B-cell lymphoma, the majority will not respond and will have a poor prognosis,” he noted.

Boom in Bispecifics

The ever-expanding list of bispecific antibodies in lymphoma “is a good problem to have,” he said, noting the need for multiple options since the prognosis of this cancer is poor. And it is not yet clear whether there are appreciable differences among these new agents. “All bispecific antibodies are active in diffuse large B-cell lymphoma; however, there appear to be some differences in terms of efficacy, dosing, and logistics,” according to Dr. Chavez.

Glofitamab and epcoritamab have similar efficacy (and are perhaps a bit better than odronextamab), but the former is a time-limited therapy, which is an advantage. The need to administer obinutuzumab prior to glofitamab seems to add some complexity to the treatment. Nevertheless, clinicians should be familiar with this antibody, as it is approved for other conditions (chronic lymphocytic leukemia, follicular lymphoma), he said.

Primarily because of glofitamab’s fixed duration of treatment and its similar efficacy and toxicity profile, Dr. Chavez maintained most hematologists would prefer glofitamab over epcoritamab in this disease. “But it will also depend on their familiarity with the drug,” he said, noting that oncologists involved in the pivotal studies may be most comfortable. Clinicians at academic institutions familiar with CAR T-cell therapy and bispecific agents should have no issues managing the toxicities, he said, but clinicians elsewhere will have “a learning curve” in using these drugs. “Therefore, there should be great focus on education to providers and for developing systems or programs in community hospitals once these agents are available,” he added.

Sequencing Considerations

In light of a growing number of treatment options beside bispecifics—including CAR T-cell therapy, polatuzumab vedotin-piiq, loncastuximab tesirine-lpyl, and tafasitamab-cxix—“the exact sequencing of treatments will be challenging, especially with the lack of formal trials comparing these agents,” Dr. Chavez said. Since he belongs to an academic center with CAR T-cell capabilities, he said his first choice for relapsed or refractory diffuse large B-cell lymphoma would be CAR T-cell therapy due to its proven efficacy and its long-term supportive data. “I would probably reserve glofitamab for relapses post–CAR T. For the rare patient who is not a candidate for CAR T, glofitamab could be used first,” he said.

DISCLOSURE: Dr. Chavez reported financial relationships with TG Therapeutics, BeiGene, Epizyme, AstraZeneca, MorphoSys/Incite, Adicet, Kite Pharma, Genmab, and AbbVie.

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