Addressing Limitations to Clinical Trial Development for Lymphoma Treatment

In an interview with CancerNetwork®, Neha Mehta-Shah, MD, MSCI, associate professor in the John T. Milliken Department of Medicine in the Division of Oncology at the Washington University Medical School in St Louis, Missouri, discussed challenges related to developing clinical trials to treat rarer lymphoma subtypes.

She began by explaining that rare lymphomas are often lumped together to better understand and categorize them when conducting clinical trials. Citing marginal zone lymphoma as an example, Mehta-Shah expressed that although marginal zone lymphoma consists of numerous disease subtypes that have different biological drivers and different propensities to affect disparate areas of the body, they all end up being lumped into a single cohort within clinical trials.

Furthermore, she remarked that to effectively understand the impact of a therapy on a particular disease subtype, subgroup analyses have to be conducted. These subgroup analyses end up representing a small sample of patients, which can present concerns when treating patients with a rare disease subtype.

Mehta-Shah concluded by suggesting that retrospective studies and real-world registry studies may be necessary to guide clinical decision-making or develop national guidelines, despite less reliance on these types of studies in other areas of medicine.

Transcript:

Sometimes we have these rare lymphomas, and in order to better understand them and categorize them, [they] are put together in 1 category, but they usually encompass more than 1 type of disease. Marginal zone lymphoma is a perfect example of that, where patients can have marginal zone lymphoma but there are multiple subtypes of marginal zone lymphoma: primary cutaneous marginal zone lymphoma, splenic marginal zone lymphoma, nodal marginal zone lymphoma, or mucosal-associated marginal zone lymphoma.

These are fundamentally different diseases. They have different biological drivers. They have a different propensity to affect different areas of the body, and we treat these differently. Because marginal zone lymphomas are rare, most studies in marginal zone lymphoma encompass all these subtypes. Helping a patient understand how a particular drug or therapy is going to work for them relies on us to then look at those data specific to that patient and do a subgroup analysis. Usually, those numbers get small in helping to understand the likelihood of response or the duration of response for a particular patient.

While we do not rely on retrospective studies in all areas of medicine to inform our practice in rare diseases, sometimes retrospective studies...[or] real-world registry type of studies may be the best type of information we have to help guide our clinical decision-making or inform the development of national guidelines.