ASH 2022: New Clinical Data Challenge Long-held Assumptions

NEW ORLEANS — In addition to news on the latest in clinical care and drug development, some eyebrow-raising findings that challenge long-held but untested assumptions are promised from the annual meeting of the American Society of Hematology.

The conference starts in New Orleans on Saturday, but a sample of what is to come was given last week in a preview media briefing, moderated by Mikkael A. Sekeres, MD, from the University of Miami Miller School of Medicine. Sekeres, who recently authored a book on the FDA and how it regulates drug approvals, also serves as chair of the ASH Committee on Communications.

“Feeding Our Patients Gruel”

Sekeres said that he’s particularly excited about a multicenter randomized trial showing that patients who have neutropenia after a stem cell transplant don’t have to be stuck eating a bland diet  (Abstract 169).

“We for years have been essentially feeding our patients gruel in the hospital, and these are folks who have to be hospitalized for a stem cell transplant or in my case – I’m a leukemia specialist — for acute leukemia, for 4-6 weeks. The neutropenic diet consists of the blandest food you can imagine, with nothing to really spice it up.”

He noted that a neutropenic diet is so unpalatable that family members often sneak food into patient rooms, and “for years we’ve never seen adverse outcomes in any of those folks who instead of having mashed potatoes and oatmeal ate a corned beef sandwich for dinner.”

Now, the results from this trial “actually give us license to finally allow patients to eat whatever they want,” he said.

Practice-Changing Data

Another two presentations that ASH experts said are sure to change clinical practice include the finding that high-dose methotrexate does not reduce the risk for central nervous system (CNS) relapse in children with acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (Abstract 214), and a common-wisdom-defying study showing that intensive chemotherapy in an attempt to achieve remission before a stem cell transplant in adults with relapsed or refractory acute myeloid leukemia (AML) did not result in better outcomes compared with sequential conditioning and immediate transplant (Abstract 4).

Premature Aging in HL Survivors

ASH President Jane N. Winter, MD, from the Feinberg School of Medicine at Northwestern University in Chicago, who also spoke at the briefing, highlighted a study that followed adult survivors of pediatric Hodgkin lymphoma. This study, from St. Jude Children’s Research Hospital in Memphis and the Wilmot Cancer Institute at the University of Rochester, New York, found that these adult survivors are at significantly elevated risk for epigenetic age acceleration accompanied by neurocognitive deficits when compared with controls.(Abstract 902)

“This is an area that is very near and dear to my heart,” she said. “Much of my career has focused on reducing the therapy to reduce the long-term consequences of treatments. Pediatricians have been very much wedded to very intensive therapies and tend to incorporate radiation more commonly in their treatment strategies for children than we do in adults.”

Winter noted that although clinicians focus primarily on the link between mediastinal radiation and long-term adverse events such as breast cancer, “now we’re shedding a light on the neurocognitive deficits, which I think are underappreciated. Being able to screen for this impact of our treatment and perhaps then develop strategies to deal with it or prevent it will have very wide-ranging impact.”

Inherited Thrombophilia and Miscarriage

Cynthia E. Dunbar, MD, chief of the Translational Stem Cell Biology Branch at the National Heart, Lung and Blood Institute in Bethesda, Maryland, who also spoke at the briefing, said that one of the abstracts most important to her practice is a study concerning pregnancy. It showed that low-molecular-weight heparin did not prevent miscarriage in pregnant women with confirmed inherited thrombophilia who had two or more prior pregnancy losses compared with standard surveillance. (Abstract LBA-5).

“This is not my field at all; on the other hand, as a hematologist and a woman, that’s what my emails in the middle of the night and my panicked phone calls are often about. Once somebody has one miscarriage, especially if they feel like they’re already over 30 and the clock is ticking, there’s a huge emphasis and a huge amount of pressure on obstetricians to basically work up for everything, kind of a shotgun [approach],” she said.

Those workups may reveal genetic mutations that are associated with mild elevations in risk for clotting, and as a result some pregnant women are put on anticoagulation therapy, which can cause complications for both pregnancy and delivery. The findings from this study don’t solve the problem of spontaneous pregnancy loss but they at least rule out inherited thrombophilia as a preventable cause of miscarriages, Dunbar said.

Another potentially practice-changing abstract is a study showing that in younger adults with mantle cell lymphoma, the addition of the Bruton’s tyrosine kinase inhibitor ibrutinib (Imbruvica) to induction therapy and as maintenance with or without autologous stem cell transplant had strong efficacy and acceptable toxicity.(Abstract 1)

“The results show that the ibrutinib-containing regimen without transplant is at least as good as the current standard of care with transplant.” Winter said. “Additional follow-up will be required to show definitively that an autotransplant is unnecessary if ibrutinib is included in this treatment regimen.”

Health Equity Challenges

In addition to the more clinical abstracts, ASH 2022 will feature sessions on addressing challenges in health equity, including an abstract on social determinants of health and pulmonary embolism treatment and mortality (Abstract 140); the impact of lab-based eligibility criteria by race/ethnicity in clinical trials for diffuse large B-cell lymphoma (Abstract 850); associations between non-European ancestry and low socioeconomic status with the receipt of HLA-disparate allografts (Abstract 127); and an analysis of the use worldwide of hematopoietic stem cell transplantation for patients with acute myeloid leukemia (Abstract 3638).

Hybrid Meeting

All told, ASH 2022 will feature nearly 5000 abstracts presented in a hybrid live and virtual format. On-site attendees will be required to provide proof of vaccination against COVID-19 and will also be required to wear masks in all public areas.

American Society of Hematology (ASH) 2022 Annual Meeting & Exposition: December 10-13, 2022.

Neil Osterweil, an award-winning medical journalist, is a long-standing and frequent contributor to Medscape.

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