ASH 2022 to Put Focus on Long-term Outcomes and What Treatments “Are Really Worth It”

From final results in the ALPINE trial for zanubrutinib in chronic lymphocytic leukemia (CLL) to findings that could end bland hospital food for patients undergoing stem cell transplant, the science at this weekend’s 2022 American Society of Hematology (ASH) Annual Meeting & Exposition puts the focus on what’s best for patients over the long haul, according to ASH leaders who previewed the upcoming meeting.

Presentations at the meeting, to be held at the Ernest N. Morial Convention Center in New Orleans, Louisiana, cover a range of clinical and quality of life subjects, with a number of abstracts addressing themes of health equity, maternal health, and pediatric care. ASH officials report that the meeting will feature nearly 5000 abstracts, and that most attendees will participate in person for the first time since the start of the pandemic. A virtual option remains available.

In a press briefing November 30, 2022, ASH Secretary Cynthia E. Dunbar, MD, chief of the Translational Stem Cell Biology Branch within the Intramural Research Program of the National Heart, Lung, and Blood Institute at the National Institutes of Health (NIH) in Bethesda, MD, said that this year’s meeting will bring greater focus to the long-term impact on patients of newer targeted therapies, and gene and cell therapies.

“There’s more and more emphasis on outcomes on financial toxicity or financial modeling, as well as on patient-reported outcomes and quality of life,” Dunbar said, and these themes will be reflected at the meeting. “As we come up with better and better scientifically supported and active treatments, [we have] to figure out which ones are really worth it, and which ones are the best, long term.”

ASH President Jane N. Winter, MD, professor of medicine in hematology/oncology at Northwestern University’s Feinberg School of Medicine, concurred. During the preview session, Winter reviewed a set of abstracts that challenge conventional thinking in hematology and noted, “Some of the things that we've been doing for quite some time, without good evidence aren't, in fact, the best thing to be doing for our patients.”

Winter said the meeting reflects hematology’s current focus “more on survival, quality of life, cost, the big picture items—not what the complete response rate is.”

Starting Off With Health Equity

Early Saturday, ASH will lift the embargo on presentations about health equity, featuring the following:

• A presentation on racial differences in the use of advanced therapies for pulmonary embolism, to be presented by Mary Cushman, MD, of the University of Vermont;
• Matthew J. Maurer, DSc, of Mayo Clinic, will present an examination of how lab-based criteria for inclusion in clinical trials for diffuse large B-cell lymphoma may affect participation among non-White patients;
• Warren Fingrut, MD, of Memorial Sloan Kettering Cancer Center, will present an analysis of how the relationship between non-European ancestry and low socioeconomic status plays out in the process of matching allograft recipients for bone marrow transplant; and
• Molly Tokaz, MD, of Fred Hutchinson Cancer Center, will present data on how the worldwide rise in the use of hematopoietic stem cell transplants to treat acute myeloid leukemia, a particularly aggressive disease, is not being felt evenly across populations.

Clinical Highlights

Saturday’s program will feature results from ADVANCE IV, a phase 3 randomized controlled trial involving intravenous (IV) efgartigimod, a novel treatment for patients with the platelet disorder refractory immune thrombocytopenia. This condition causes platelets to be destroyed and cleared from the blood due to interference from abnormal immunoglobulin proteins. Efgartigimod is a neonatal Fc receptor blocker, which works by blocking the pathway that recycles immunoglobulins and releases the troublesome proteins back into the bloodstream. Sponsors of efgartigimod, approved as Vyvgart to treat myasthenia gravis, have already announced positive topline results and are developing a subcutaneous formulation, with data due in early 2023. Georgetown University’s Catherine D. Broome, MD, will present findings at a plenary session.

Also Saturday, Ajai Chari, MD, of Mount Sinai School of Medicine, will present results from the phase 1/2 MonumenTAL-1 study for talquetamab in patients with relapsed/refractory (R/R) multiple myeloma. This first-in-class, off-the-shelf bispecific antibody binds to both tumor cells and T cells, as Dunbar explained; it targets both the G-protein-coupled receptor family C group 5 member D (GPRC5D) and CD3 receptors “to facilitate myeloma tumor cell killing by the T cells.” The drug, developed by Janssen, has previously received a breakthrough therapy designation from FDA.

Tuesday’s late-breaking session will feature the final analysis from the phase 3 ALPINE study, where Jennifer R. Brown, MD, PhD, of Dana-Farber Cancer Institute, will present head-to-head results in progression-free survival (PFS) between Bruton tyrosine kinase inhibitors zanubrutinib (Brukinsa, BeiGene) and ibrutinib (Imbruvica, Janssen) in relapsed/refractory CLL and small lymphocytic leukemia. In the preview call, Dunbar said that while ibrutinib was “revolutionary” in treating CLL, “it’s not effective in all patients, and it has some significant side effects, particularly to the heart.” She said the data will highlight better PFS and lower discontinuation rates in the zanubrutinib arm. “This is good news for patients with CLL unable to tolerate ibrutinib and may eventually impact on all patients with CLL,” Dunbar said.

Other data coming during Tuesday’s late-breaking session are results involving blinatumomab in newly diagnosed adult patients with B-cell acute lymphoblastic leukemia (B-ALL). Mark R. Litzow, MD, of Mayo Clinic, will present findings from the ECOG-ACRIN E1910 randomized phase 3 National Cooperative Clinical Trials Network Trial. Dunbar noted that adults with B-ALL have far worse outcomes than children and almost all adults require an allogeneic stem cell transplant following months of chemotherapy to have any hope of a cure. The current study shows that the blinatumomab treatment produces superior results, she said. “This exciting result will likely change the approach to these patients and potentially allow avoidance of allogeneic transplantation for many.”

Results for Mothers and Children

Another late-breaking abstract, the ALFIE2 study, examined the use of low-molecular-weight heparin vs standard pregnancy care for women with recurrent miscarriage and inherited thrombophilia. Dunbar keyed on this abstract as one of her favorites of the meeting—despite it being out of her field of expertise—because of its importance to women’s health. Impaired blood supply and thrombosis in the placenta have been hypothesized to play a role in recurrent miscarriage, she noted, and the question of how to manage this has worried hematologists and obstetricians for decades. The trial results being presented focus on the 5% of women with recurrent pregnancy loss that have specific situation known to result in increased risk of venous blood clots, Dunbar said, whether or not they are pregnant. Low-molecular-weight heparin was not found to improve miscarriage rates, and Dunbar said presenters “will discuss the implications of this disappointing but definitive result for the screening and treatment of women in this situation.”

Winter keyed on a study that uses long-term data from St Jude Children’s Hospital to evaluate how treatment for pediatric Hodgkin lymphoma can affect patients’ neurocognitive function over their lifetime. AnnaLynn M. Williams, PhD, MS, of Wilmot Cancer Institute at the University of Rochester, will present these findings Monday, which focus on epigenetic age acceleration as an important biomarker that may signal risk of early onset of dementia in these patients.

From Italy, a Study to Let Patients Eat “Whatever They Want”

Preview call moderator Mikkael Sekerkes, MD, of the Sylvester Comprehensive Cancer Center at the University of Miami, pointed to a study about the neutropenic diet as one that is sure to generate interest among doctors and patients alike. Federico Stella, MD, will present findings from the University of Milan, Italy, which found that that the bland diet patients receive to reduce the risk of infection offers no real advantage. Sekerkes predicts this study will have a major impact on patient care. “For years, we’ve been essentially feeding our patients gruel in the hospital,” he said, pointing out that it’s known that family members sneak food into patients—with no documented adverse effects.

“So, this trial actually gives us license to finally allow patients to eat whatever they want,” Sekerkes said. “I think this is going to massively improve the quality of life of people who are spending a month or more in the hospital for very intensive therapies for their hematologic malignancies.”