Advancing Research and Clinical Trials Across Key Lymphoma Populations

As part of a visit to Yale Cancer Center in New Haven, Connecticut, CancerNetwork® spoke with a variety of experts in hematologic oncology about key initiatives they are organizing at their institution to help improve outcomes across different lymphoma populations. Specifically, Shalin Kothari, MD, detailed important considerations in the mantle cell lymphoma field while Tarsheen Sethi, MD, MSc, discussed work dedicated to T-cell lymphoma management.

Kothari, an assistant professor of medicine (hematology) at Yale University, emphasized making an accurate diagnosis via hematopathology and determining predictive molecular biology markers that may inform treatment strategies in mantle cell lymphoma. Additionally, he outlined a few ongoing studies at Yale that are assessing novel therapeutic combinations across multiple treatment lines and settings, describing a willingness to “push the envelope” and provide options to patients whenever they require care.

Sethi, an assistant professor of medicine (hematology) at Yale School of Medicine, stressed the importance of evaluating how deeply minimal residual disease (MRD) and progression-free survival (PFS) benefits can occur among those with different lymphoma subtypes. She noted her passion for treating patients with T-cell lymphomas, stating that multiple trials are ongoing in the frontline and relapsed/refractory settings.

Transcript:

Kothari: Specifically, for mantle cell lymphoma, I would say that it’s [quite] important to make sure, first of all, that the diagnosis is appropriate. Often, it happens that we get patients for second opinions, we get hematopathology review, and we find features of mantle cell lymphoma or some other non-Hodgkin lymphoma, which ended up being mantle cell lymphoma. The reason for those is that there are some mantle cell lymphomas that are CCND1 negative. And in those situations, it requires a good hematopathologist to make that diagnosis. That’s No. 1.

No. 2 is to spend time in figuring out the exact molecular biology that impacts the treatment, what we call predictive markers. It’s [quite] important to get a karyotype, to get FISH [fluorescence in situ hybridization] for certain probes, and to check for at least TP53, if not others. Here, we typically end up sending next-generation sequencing with [more than] 100 genes to understand the molecular features of that mantle cell lymphoma.

And then, particularly at Yale, we have clinical trials ongoing. In frontline [mantle cell lymphoma], we have loncastuximab tesirine-lpyl [Zynlonta] with zanubrutinib [Brukinsa] and rituximab [Rituxan], which is being studied. In addition, we have a trial of zanubrutinib with rituximab as part of the Alliance [for Clinical Trials in Oncology] trial [NCT05976763]. I have multiple relapsed/refractory trials in the second, third, and fourth line, which includes bispecific antibodies and CAR T-cell therapies. We are always trying to push the envelope and trying to have those options available for patients when they need it. In terms of just a quick tidbit for the patients, I would say that it’s important to get second opinions if needed, especially in the second, third, or fourth line of therapy with mantle cell lymphoma, because it can get very nuanced. It’s a niche field with a lot of minutiae that if you take care of [them], then we can have a significant impact on outcomes.

Sethi: It’s [quite] important that, as we are getting all these data in all these different subtypes of lymphoma, to remember that in some diseases—for example, chronic lymphocytic leukemia—we still want to try to figure out how much of a deep MRD and a [PFS] benefit [we can achieve]. Is it worth going for as compared with just truly sequencing treatment, where we do have these options that can last patients a long time because these patients will need multiple options over time? As far as my research is concerned, especially at Yale, we are passionate about treating patients with T-cell lymphomas. This is a rare disease, but again, a lot of research is needed in this field. Many patients are not doing as well. We continue to have multiple clinical trials in T-cell lymphoma, both in the front line and in the relapsed/refractory setting.