Upfront Treatment and Early Intervention to Get Attention at ASH

For several years, the therapeutic leaps unveiled at the American Society of Hematology Annual Meeting & Exposition (ASH) focused on patients who had exhausted all other options—with the big news coming from chimeric antigen receptor (CAR) T-cell therapy or bispecific T-cell engagers (BiTEs).

ASH 2024 will have important news for those therapies, but this time the excitement in San Diego, California, December 7-10, 2024, involves bringing the most advanced therapies into earlier lines of care—or even to patients who are precancerous, with “smoldering” disease.

On Monday, physicians will learn more about a potential option for patients with untreated chronic lymphocytic leukemia (CLL) when Jennifer R. Brown, MD, PhD, of Dana-Farber Cancer Institute presents results from the phase 3 AMPLIFY trial, which involves a fixed-duration regimen of the Bruton tyrosine kinase (BTK) inhibitor acalabrutinib (Calquence, AstraZeneca) and venetoclax (Venclexta, AbbVie), with or without obinutuzumab (Gayza) vs chemoimmunotherapy.

Results from the phase 3 AQUILA study, also being presented Monday but released Sunday, will examine whether patients with high-risk smoldering multiple myeloma (SMM) benefit from treatment with daratumumab vs active monitoring, which would represent a shift in the way these patients are managed—and elevate the need to work more aggressively to identify these patients. Management of SMM has been hotly debated and was the focus of an International Myeloma Society session in September that highlighted how SMM presents differently among Black patients, calling for different approaches to care.

Word will come first thing Saturday on results of a study from the Children’s Oncology Group, which examined survival benefits of blinatumomab and chemotherapy for newly diagnosed pediatric patients with B-acute lymphoblastic leukemia (B-ALL). Amgen, the maker of this BiTE, sold as Blincyto, has highlighted that this is the 10th anniversary of its approval.

Quality of Life—for Patients and Physicians

Of interest to managed care audiences, results from the use of epcoritamab in patients with heavily pretreated CLL appear to offer good news about strong responses alongside marked improvement in toxicity. Alexey Danilov, MD, PhD, of City of Hope, will present these findings.

A fascinating analysis of where oncology and hematology fellows train and ultimately settle down to establish practice is the subject of an abstract led by Vishwanath Anil, MD, of Wellstar Health. The project tracks fellows’ location patterns against the insurance status of the patients they will treat.

Finally, among the many ASH symposia is Monday’s “Placing the Brakes on Accelerated Aging,” which notes the prevalence of hematological malignancies among older adults and will examine the distinction between chronological and biological aging assessments for hematologic disease. Organizers say these distinctions “will be crucial for the identification of targets and development of therapies for this specific population.”

Late-Breaking Abstracts

Tuesday’s late-breaking session always offers practice-changing possibilities, and 2024 will be no exception. Three studies of note are:

• Results from the phase 3 inMIND study, evaluating tafasitamab plus lenalidomide and rituximab for R/R follicular lymphoma. This study looked at the effective of dual monoclonal antibodies, CD20 and CD19, and results show significant reduction in the risk for disease progression or death compared with therapies that target CD20 alone.
• An abstract involving a key mechanism of myeloproliferative neoplasms, titled “Andean enriched NFKB1 haplotype reduces inflammation and improves response to ropeginterferon Alfa-2b in polycythemia vera essential thrombocythemia."
• This study will raise new possibilities for treatment management through the measurement of minimal residual disease (MRD): "Lack of benefit of autologous hematopoietic cell transplantation (auto-HCT) in mantle cell lymphoma patients in first complete remission with Undetectable MRD: Initial report from the ECOG-ACRIN EA4151 phase 3 randomized trial.” MRD assessments can identify those patients who respond to initial chemoimmunotherapy, allowing them to skip high-dose chemotherapy and autologous stem cell transplantation.

AI in Hematology

Artificial intelligence (AI) has made conference agendas across health care this year, and ASH is no exception: it is the meeting theme, with sessions on AI applications in genomics, diagnostics, clinical workflows, and decision-making. Sessions include:

• The Application of Artificial Intelligence in Hematological Diagnostics
• The Role of AI in Hematological Practice: The Good, the Bad, and the Ugly

Other Notable Studies

A generation after the 9/11 terrorist attacks on the World Trade Center, a study being presented has homed in on the potential cause of increased risk of leukemia among first responders exposed to high levels of dust and carcinogens in Lower Manhattan. Collaborators from Albert Einstein College of Medicine and Montefiore Medical Center in the Bronx, along with the Leukemia and Lymphoma Society and the University of Vermont, used deep sequencing to track a cohort of 988 first responders and learned that clonal hematopoiesis had higher prevalence among those exposed at the World Trade Center. Results will be presented Monday.

Follow-up data on landmark therapies approved a year ago on the eve of ASH 2023 will be presented this weekend. Stacey Rifkin-Zenenberg, DO, of Hackensack Meridian Health, will present data on early predictors on which patients with sickle cell disease response to lovotibeglogene autotemcel (Lyfgenia, bluebird bio) on Sunday. Haydar Frangoul, MD, of Sarah Cannon Research Institute at Children’s Hospital, TriStar Centennial in Nashville, will present “Durable Clinical Benefits with Exagamglogene Autotemcel for Severe Sickle Cell Disease,” for exa-cel (Casgevy, Vertex), on Monday.