Editorial – ASH 2024

Portrait © Uni Klinik Ulm – Stephan Stilgenbauer, MD, Comprehensive Cancer Center Ulm, University of Ulm, Ulm, Germany

Portrait © private – Anna Fenzl, PhD, memo inHaematology, Springer-Verlag GmbH, Vienna, Austria

Dear Colleagues,

The 66^th Annual Meeting of the American Society of Hematology (ASH), held as a hybrid event from December 7^th to 10^th, 2024, in San Diego, California, USA, set a new benchmark with over 7,950 abstracts accepted for presentation. This special memo inHaematology issue highlights the most significant advancements from ASH 2024 in the fields of chronic lymphocytic leukemia, follicular lymphoma, Waldenström’s macroglobulinemia, and mantle cell lymphoma, offering a concise guide to the discoveries set to transform clinical practice.

In chronic lymphocytic leukemia (CLL), fixed-duration therapies took center stage, signaling a shift towards time-limited, effective treatment strategies. The AMPLIFY trial showcased the remarkable efficacy of acalabrutinib, venetoclax, with or without obinutuzumab combinations, achieving prolonged progression-free survival even in high-risk populations such as those with unmutated IGHV or complex karyotypes. These results support the double and triple combination as a new standard for a broad population of fit, treatment-naïve patients. Complementary evidence from the SEQUOIA study emphasized the durable benefits of zanubrutinib over chemoimmunotherapy, offering superior outcomes in diverse genetic subgroups. For relapsed or refractory cases, the BRUIN CLL-321 trial established pirtobrutinib as an effective and well-tolerated option for patients previously treated with covalent BTK inhibitors.

In addition to these advancements, the field witnessed the rise of novel therapeutic agents addressing treatment resistance and intolerance in CLL. BTK degraders such as NX-5948 and BGB-16673 demonstrated the ability to target BTK-mutated disease, with early results showing impressive efficacy across high-risk patient cohorts. Moreover, the ongoing exploration of MRD-driven treatment approaches, as seen for the BOVen regimen and pirtobrutinib-based triplet therapy, promises to redefine personalized care.

For follicular lymphoma, innovation was driven by a focus on improving efficacy and patient convenience. Epcoritamab, a CD3xCD20 bispecific antibody, demonstrated exceptional depth and durability of response in combination with rituximab and lenalidomide, even in patients with double-refractory disease. Mosunetuzumab, offered as a subcutaneous formulation, provided an alternative to intravenous therapy, maintaining efficacy while enhancing patient convenience. Furthermore, zanubrutinib combined with obinutuzumab in the ROSEWOOD study achieved significant improvements in progression-free survival, establishing itself as a robust option for refractory disease. Adding to these advances, BTK degraders like BGB-16673 offered hope for patients with BTK inhibitor resistance.

In Waldenström macroglobulinemia (WM), personalized approaches continued to evolve, driven by both real-world and clinical trial data. The ASPEN extension study reaffirmed the long-term safety and efficacy of zanubrutinib, solidifying its role as a key therapy in treatment-naïve and relapsed patients. Exciting progress was made with novel fixed-duration regimens, such as pirtobrutinib in combination with venetoclax, which achieved deep responses and minimized cumulative toxicity. The WhiMSICAL registry provided unique insights into real-world treatment patterns and outcomes, revealing valuable information about how BTK inhibitors and chemoimmunotherapy compare in clinical practice. Therapies for heavily pretreated patients also took the spotlight, with loncastuximab tesirine, a CD19-targeting antibody-drug conjugate, demonstrating high response rates even in those with complex genetic profiles. Meanwhile, BTK degraders like BGB-16673 showed broad activity, including in patients with resistance to prior BTK inhibitors. Additionally, zanubrutinib’s success in addressing the Bing-Neel syndrome highlighted its CNS-penetrating capability, offering new hope for patients with this rare and challenging WM manifestation. Together, these advances reflect a move toward greater personalization and expansion of therapeutic options, ensuring more effective treatments for a wider range of WM patients.

For mantle cell lymphoma, breakthroughs focused on chemotherapy-free regimens and MRD-driven strategies. The update of the TRIANGLE study confirmed superior efficacy and tolerability of consolidation with ibrutinib over high-dose therapy and transplant with impressive overall survival advantage. The OASIS II trial delivered remarkable MRD negativity rates with ibrutinib, venetoclax, and anti-CD20 antibody therapy, setting a high bar for induction treatment. Meanwhile, response-adapted strategies in the ALTAMIRA study offered insights into managing elderly patients effectively, while the antibody drug conjugate zilovertamab vedotin showed promise for relapsed or refractory cases. These studies highlight the potential for individualized approaches, but also underscore the need for continued innovation in this challenging disease.

As we reflect on these discoveries, let us embrace the opportunities they offer to refine standards of care and improve patient lives. Together, we are advancing science and transforming the future of hemato-oncology.

Under the motto “Never stop educating yourself,” Stephan Stilgenbauer, MD, Anna Fenzl, PhD, and the memo inHaematology team wish you happy reading!

© 2024 Springer-Verlag GmbH, Impressum

Disclosures: Stilgenbauer: Janssen: Membership on an entity’s Board of Directors or advisory committees, Other: Travel support, Research Funding, Speakers Bureau; Hoffmann-La Roche: Membership on an entity’s Board of Directors or advisory committees, Other: Travel support, Research Funding, Speakers Bureau; GSK: Membership on an entity’s Board of Directors or advisory committees, Other: Travel support, Research Funding, Speakers Bureau; Gilead: Membership on an entity’s Board of Directors or advisory committees, Other: Travel support, Research Funding, Speakers Bureau; Galapagos: Membership on an entity’s Board of Directors or advisory committees, Other: Travel support, Research Funding, Speakers Bureau; BMS: Membership on an entity’s Board of Directors or advisory committees, Other: Travel support, Research Funding, Speakers Bureau; BeiGene: Membership on an entity’s Board of Directors or advisory committees, Other: Travel support, Research Funding, Speakers Bureau; AstraZeneca: Membership on an entity’s Board of Directors or advisory committees, Other: Travel support, Research Funding, Speakers Bureau; Amgen: Membership on an entity’s Board of Directors or advisory committees, Other: Travel support, Research Funding, Speakers Bureau; Lilly: Membership on an entity’s Board of Directors or advisory committees, Other: Travel support, Research Funding, Speakers Bureau; Novartis: Membership on an entity’s Board of Directors or advisory committees, Other: Travel support, Research Funding, Speakers Bureau; Sunesis: Membership on an entity’s Board of Directors or advisory committees, Other: Travel support, Research Funding, Speakers Bureau; AbbVie: Membership on an entity’s Board of Directors or advisory committees, Other: Travel support, Research Funding, Speakers Bureau.

Disclosures: Fenzl: none.