Editor's Note：Significant progress has been made in the treatment of T-cell lymphomas in recent years. However, challenges persist in managing relapsed/refractory disease, selecting optimal therapies, and determining the best treatment sequencing for patients. To address these issues, the 2024 American Society of Hematology (ASH) Annual Meeting featured an educational session titled Addressing Unmet Needs in T-Cell Lymphomas. This session brought together leading experts to provide insights and practical guidance based on the latest research and clinical experiences. Hematology Frontier had the privilege of speaking with session chair Dr. Neha Mehta-Shah from Washington University’s Siteman Cancer Center. In this discussion, she shared her perspectives on unmet needs, treatment strategies for relapsed/refractory peripheral T-cell lymphoma (PTCL), innovative therapies, and the role of autologous and allogeneic transplants in PTCL.1. Unmet Needs in T-Cell Lymphoma Management
Hematology Frontier: This session at the ASH Annual Meeting focused on Addressing Unmet Needs in T-Cell Lymphomas. As the session chair, could you outline the key unmet needs in T-cell lymphoma management today?
Dr. Neha Mehta-Shah: There are many unmet needs in the T-cell lymphoma field. One critical area is the need for more effective and better-tolerated therapies, particularly for relapsed/refractory T-cell lymphoma. Unfortunately, most patients experience relapse after initial therapy. When this happens, the currently available treatments can have efficacy limitations and tolerability issues.
Another significant challenge is improving cure rates with frontline therapies, though this was not the focus of today’s session. A similar unmet need exists in cutaneous T-cell lymphomas. While we have numerous available drugs, selecting the right therapy for each patient and optimizing the sequencing of treatments—especially with a focus on improving quality of life—remains an area that requires attention.
2. Treatment Strategies and Innovations in Relapsed/Refractory PTCL
Hematology Frontier: This session also highlighted peripheral T-cell lymphoma (PTCL). Could you discuss the current strategies for managing relapsed/refractory PTCL and some of the innovative therapies and drugs on the horizon?
Dr. Neha Mehta-Shah: While the available therapies for PTCL differ across countries, the U.S. currently has FDA-approved options including histone deacetylase (HDAC) inhibitors such as belinostat and romidepsin, the CD30-targeted antibody-drug conjugate brentuximab vedotin, and pralatrexate. These form the backbone of our current treatment approach.
However, ongoing research through single-center, multicenter, and industry-sponsored studies has introduced other promising drugs for T-cell lymphoma. Some of these therapies have already been incorporated into NCCN guidelines, including PI3K inhibitors, hypomethylating agents, and JAK-STAT inhibitors. Additionally, EZH2 inhibitors and more advanced JAK inhibitors are showing potential. These innovations may significantly expand our treatment options for patients with relapsed or refractory disease.
3. Role of Transplants in PTCL Management
Hematology Frontier: How do you view the role of autologous and allogeneic transplants in PTCL? Which patients are suitable for these procedures, and what are the key considerations for timing and management pre- and post-transplant?
Dr. Neha Mehta-Shah: The role of transplantation in PTCL is complex, particularly for the most common subtypes. In my clinical practice, I typically consider autologous transplant during the first remission. Dr. Dräger presented data at the meeting indicating that, for chemotherapy-sensitive subtypes such as PTCL-not otherwise specified (PTCL-NOS), ALK-negative anaplastic large-cell lymphoma (ALCL), and angioimmunoblastic T-cell lymphoma (AITL), undergoing autologous transplant in the first remission could improve long-term outcomes by up to 20%.
Ongoing studies, including a U.S. multicenter trial and research by the French LYSA group, are randomizing patients to autologous transplant versus no transplant in the first remission. These studies may ultimately resolve the debate. For now, however, I continue to favor autologous transplant in first remission in my practice.
For allogeneic transplant, the data indicate that, while it improves disease control when performed in first remission, the associated toxicities often offset these benefits. As a result, we generally avoid allogeneic transplant in first remission, except for specific diseases like hepatosplenic T-cell lymphoma or adult T-cell leukemia/lymphoma (ATLL).
In cases of relapse, however, allogeneic transplant remains a potentially curative option. For relapsed patients with good performance status who are eligible, we strongly recommend considering allogeneic transplant.
Conclusion
Dr. Neha Mehta-Shah’s insights underscore the progress and challenges in managing T-cell lymphomas. While advancements in drug development, innovative therapies, and transplantation have expanded treatment options, unmet needs remain, particularly in improving frontline cure rates, addressing relapsed/refractory disease, and optimizing therapy sequencing. With ongoing clinical trials and emerging therapies, the future holds promise for enhanced outcomes and quality of life for T-cell lymphoma patients.
