Exploring the Rare Lymphoma Landscape

In this episode, CancerNetwork® spoke with 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, MO, about the clinical landscape for patients undergoing treatment for rare lymphomas.

According to Mehta-Shah, one of the most promising developments in rare lymphomas is the improvement in diagnostic capabilities. Mutational profiling and genetic sequencing now allow for a more precise understanding of cancer cell biology, which has paved the way for the development of innovative therapies such as immunotherapy and oral targeted agents.

However, the rarity of these lymphomas creates substantial hurdles. The limited number of experienced specialists and the scarcity of data from large-scale prospective studies make it difficult to establish standardized treatment protocols. The diagnostic process can be lengthy, often requiring biopsies to be sent to specialized laboratories for expert analysis. Furthermore, regulatory requirements, such as the FDA's preference for randomized phase 3 studies, pose challenges in conducting clinical trials for rare diseases due to the lack of suitable comparison groups.

Despite these challenges, several clinical trials and research initiatives offer optimism. In T-cell lymphoma, PI3K inhibitors and EZH2 inhibitors have shown promise, even in cases where standard chemotherapy has failed. For cutaneous T-cell lymphoma, novel antibodies targeting KIR DL2 have demonstrated durable remissions and improved quality of life. Additionally, investigators are exploring immunotherapy in earlier lines of treatment for patients with Hodgkin lymphoma to minimize long-term adverse effects and enhance quality of life.

Mehta-Shah also emphasized several future directions in the field. Improving cure rates, minimizing the long-term toxicity of current standard-of-care therapies, and developing better treatments for relapsed/refractory T-cell lymphomas, where prognoses remain poor, are critical priorities. Addressing the financial, social, and emotional burdens of a lymphoma diagnosis through patient-reported outcomes and improving access to specialized care, particularly in rural areas, are also essential.

To overcome these barriers, several innovative approaches are being explored. Artificial intelligence (AI) tools may assist pathologists in diagnosing rare diseases by integrating molecular and pathological data. Advancements in CAR T-cell therapy, including off-the-shelf products and reduced manufacturing times, may expand patient access to treatment. Additionally, the development of oral or home-based therapies may significantly reduce the burden of frequent infusions. However, the high cost of these therapies remains a significant challenge, although non-profit organizations and patient assistance programs offer some support.

In conclusion, Mehta-Shah indicated that even with significant progress in understanding and treating rare lymphomas, ongoing advocacy and collaborative efforts among patients, advocates, scientists, and clinicians are crucial to ensure continued scientific funding and improved outcomes in the field.