Advancements in research and technology are critical to improving patient care and outcomes. But with these advances, new challenges arise, particularly regarding decision-making for complex diseases like mantle cell lymphoma (MCL). This “paradox of choice,” as described by psychologist Barry Schwartz in his 2004 book of the same name, is evident in our practice, where we now have an array of therapeutic options (e.g., proteasome inhibitors, immunomodulators, and Bruton tyrosine kinase inhibitors) that can be integrated into immunochemotherapy regimens for newly diagnosed patients with MCL. With each additional choice, the complexity of treatment selection grows. For us practicing generalists who routinely care for lymphoma patients, these choices come entangled with uncertainty, akin to a tree growing beyond reach. Fortunately, a professional-level crash course awaits at today’s oral abstract sessions on indolent B-cell lymphomas (2:00 p.m. to 3:30 p.m. and 4:00 p.m. to 5:30 p.m., Mariott Marquis, Grand Ballroom 11-13), where the complexities surrounding both MCL and follicular lymphoma (FL) treatments will be demystified.
One of the highlights of the session will be the next chapter of the TRIANGLE randomized phase III trial of the academic European MCL Network, which investigates the efficacy of incorporating first-line ibrutinib plus chemo-immunotherapy. Following the #ASH22 plenary presentation and publication, we were left at a cliffhanger regarding the role of autologous transplant consolidation. Martin Dreyling, MD, the lead study author, will continue the story by answering two lingering questions: What is the long term-outcome of patients who received ibrutinib plus chemo-immunotherapy without transplant vs. the standard of care, and what does transplant add to the ibrutinib-containing arm? “These are solid data, and they hold up,” Dr. Dreyling said. “After a median of five years of follow-up … now we will provide a definite answer” (Abstract 240).
On another side of the TRIANGLE, Marco Ladetto, MD, will present a retrospective analysis of the role of rituximab maintenance, shedding light on its potential impact on the safety and efficacy of each arm of the trial (Abstract 237).
Other afternoon oral abstracts will also include findings from various trials that explore different intensities of treatment in MCL. Nina D. Wagner-Johnston, MD, will present results from the ECOG-ACRIN EA4181 study examining acalabrutinib in combination with bendamustine-rituximab and cytarabine-rituximab (Abstract 236). Additionally, David John Lewis, MD, will discuss the results of the ENRICH randomized phase III trial comparing ibrutinib plus rituximab with rituximab-chemotherapy for older, untreated patients (Abstract 235). “This study defines the standard-of-care control arm in future trials in MCL,” Dr. Lewis said. “I think the audience will be surprised by the findings.”
Numerous factors can influence and shape the shared decision-making process. What are patients’ preferences and goals? How can we balance novelty bias and the allure of “all-oral non-chemotherapy,” which may not necessarily represent the better choice? Clinicians must help patients weigh the fear of toxicity, long-term risks, short-term gains, and potential trade-offs, all while instilling confidence in their recommendations. This nuanced approach to decision-making is especially relevant in FL, where treatment options can vary based on disease burden. For patients with minimal disease, a “watch and wait” approach is considered acceptable. However, inaction may also lead to harm, as patients can experience anxiety that impacts their quality of life, thus earning this strategy the “watch and worry” pejorative across conference room hallways.
Later in the day, Noriko Fukuhara, MD, PhD, will present the results of the JOCG1411/Flora study (Abstract 338), where the efficacy of early rituximab monotherapy administration for patients with low tumor burden FL was studied in a randomized fashion, with the goal of determining whether early immunotherapy treatment can delay disease progression and thus the need for cytotoxic chemotherapy. With a more modern twist on the first-line treatment of FL, and leading the incoming wave of bispecific antibodies in the #ASH24 oral abstract sessions, Lorenzo Falchi, MD, will present the primary analysis of the Mithic-FL1 phase II trial (Abstract 340), in which mosunetuzumab, a CD20xCD3 bispecific antibody, was employed in patients with FL with a more traditional indication for starting treatment.
These and many more oral abstracts on novel therapies in the relapsed refractory setting await, including analyses of loncastuximab tesirine, epocoritamab, and yet-to-be named bi-specifics and chimeric antigen receptor T-cell (CAR-T) therapy. By the end of these sessions, the “paradox of choice” for MCL and FL treatments will be demystified, presenting clearer and more navigable strategies, equipping hematologists with the essential insights needed to deliver the highest level of patient care.
Outside of the lymphoma world, other Saturday oral abstracts to watch out for include Session 503 (2:00 p.m. - 3:30 p.m., Manchester Grand Hyatt, Grand Hall D), which will focus on the mechanistic intersection between clonal hematopoiesis, aging, and inflammation. Later in the day, be sure to attend Session 702 (4:00 p.m. - 5:30 p.m., Manchester Grand Hyatt, Grand Hall C). This session will feature basic and translational discoveries in the interplay between CAR-T therapy and myeloid biology that seek to bring the success of immune effector cells to patients with acute myeloid leukemia and other non-lymphoid neoplasms.
