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“To Do or Not to Do” in Aggressive Non-Hodgkin Lymphoma: Addressing the Controversies

December 10, 2022
Anupama Deepa Kumar, MD, and Ah-Reum (Autumn) Jeong, MD

Dr. Ah-Reum “Autumn” Jeong (@AutumnJeong) is an alum of Cornell University where she went for undergrad studies. A San Diego native, she returned to the West Coast and attended University of Southern California for medical school and residency, and UC San Diego for her fellowship. Today she is assistant clinical professor in the Division of Medicine, Department of Blood and Marrow Transplantation, at Moores Cancer Center at UC San Diego Health in La Jolla, California. Her interests include myeloma, CAR-T therapy, and bone marrow transplantation. This is Dr. Jeong’s second year on the board of ASH News Daily, having served as a Junior Author in 2021. “I did Taekwondo during college and competed regionally,” she informed us.

Dr. Anupama Deepa Kumar (@anupamakumar05) is a fellow at UC at Moores Cancer Center of UC San Diego Health. Focusing on all things malignant hematology, Dr. Kumar is an alum of Cornell University as well as Tufts University School of Medicine and Tufts Medical Center, where she completed medical school and residency, respectively. Her hometown is lovely Palo Alto, California.

For those who treat lymphoma, there are a few common dilemmas faced in the clinic on a daily basis: to administer or not to administer central nervous system (CNS) prophylaxis for diffuse large B-cell lymphoma (DLBCL); to proceed or not to proceed with autologous transplant consolidation for mantle cell lymphoma (MCL), and to perform or not to perform autologous transplant or chimeric-antigen receptor T-cell (CAR-T) therapy for relapsed DLBCL. Looking for answers? Look no further. Drs. Kate Cwynarski, Christopher Flowers, and Anita Kumar will provide clarity (and even better … flow charts for your office wall collection) during the Education Program Session Controversies in Aggressive NHL, on Saturday, December 10 (9:30 a.m.-10:45 a.m.).

An estimated 5 percent of patients with DLBCL develop the dreaded outcome of CNS relapse, often with an expected survival of less than six months. While rituximab-based regimens have improved outcomes for DLBCL, rituximab has poor CNS penetrance. Traditionally, patients deemed to be at high risk for developing CNS disease were treated prophylactically with intrathecal chemotherapy or intravenous methotrexate. How do we appropriately identify and prophylactically treat the highest-risk patients while avoiding unnecessary toxicity in the vast majority of patients who will never develop CNS relapse? Dr. Cwynarski from University College London will tackle this complex topic by reviewing the landscape of the literature and informing us about the latest risk stratification models and novel therapies with CNS penetrance.

The Controversies in Aggressive NHL session will then pivot to discuss relapsed/refractory DLBCL, led by the esteemed Dr. Flowers from MD Anderson Cancer Center and who is also receiving the ASH Mentor Award this year. Approximately 40 percent of patients with DLBCL relapse or fail to respond to first-line regimens. Unfortunately, many of these patients ultimately succumb to their lymphoma. The PARMA trial established salvage platinum-based chemotherapy followed by consolidative autologous stem cell transplantation as the standard of care in chemotherapy-sensitive transplant-eligible patients with relapsed/refractory DLBCL. More than 20 years later, the introduction of CAR-T therapy has shifted the treatment paradigm. Notably, the three pivotal trials — ZUMA-7, BELINDA, and TRANSCEND — compared the three available anti-CD19 CAR-T treatments against autologous transplantation in patients with relapsed/refractory DLBCL. Dr. Flowers will review the differences in the design of these trials, the conflicting results, and the real-world implications of these findings.

Lastly, Dr. Kumar of Memorial Sloan Kettering Cancer Center will delve into the role of upfront autologous stem cell transplantation in mantle cell lymphoma in the modern era. Autologous stem cell transplant consolidation has previously been shown to provide a significant benefit for progression-free survival, but not overall survival. Bruton tyrosine kinase (BTK) inhibitors are an established second-line treatment option, with promising results in relapsed/refractory disease and a signal for improved outcomes with early exposure. Currently, clinical trials are exploring first-line therapy using combinations of cytarabine-based regimens or bendamustine/rituximab (BR) plus targeted agents (e.g., the SHINE study investigating BR + ibrutinib). Dr. Kumar will also discuss the role of minimal residual disease monitoring to personalize therapeutic options. Also, stay tuned for the Plenary Scientific Session on Sunday, December 11, during which Dr. Martin Dreyling from LMU University Hospital in Munich will discuss the results of the TRIANGLE trial examining efficacy and safety of ibrutinib combined with standard first-line treatment or as a substitute for autologous stem cell transplantation in younger patients with mantle cell lymphoma.

The emergence of targeted therapies has broadened the available tools to combat aggressive lymphomas but has also left many questions we eagerly await answers to. We are excited to hear the debates and discussions and have already saved this session to our schedules on the 2022 ASH Annual Meeting App! Et tu, Brute?

Dr. Kumar and Dr. Jeong indicated no relevant conflicts of interest.

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