ASH Meeting: Diversity, Inclusion, Immunotherapy, and COVID-19

This year, the American Society of Hematology, better known to all as “ASH,” will be hosting its annual meeting in a hybrid format. Content will be presented both live and in person at the Georgia World Congress Center in Atlanta and also online for those who can’t or don’t want to be there in person.

Inevitably during the ongoing pandemic, the meeting will contain key sessions on COVID-19 in hematology, including a plenary presentation outlining a biologic mechanism for the increased coagulopathy with SARS-CoV-2 infections.

In addition, there will be a scientific symposium on COVID-19 vaccination in immumocompromised patients and a special moderated session summarizing nine abstracts on the science of thrombosis in COVID-19, outcomes in patients with hematologic disease, and vaccine responses.

And speaking of COVID, lest anyone forget, annual meeting attendees will be required to be fully vaccinated and masked. Free COVID-19 testing will be available at stations situated throughout the convention center.

Diversifying Care

A glimpse of some of the most exciting research to be presented at ASH 2021 was given at a pre-meeting press briefing by Mikkael A. Sekeres, MD, chair of the ASH committee on communications and chief of the Division of Hematology at the Sylvester Comprehensive Cancer Center at the University of Miami, Florida.

For example, investigators at Massachusetts General Hospital in Boston will present new data on code-status transitions among patients with poor-prognosis high-risk acute myeloid leukemia (AML) who are approaching the end of life. Their findings suggest that physician-patient discussions about the goals of care may occur too late in the course of illness for many patients (abstract 109).

“While there have been many advances in the treatment of acute myeloid leukemia, and in fact there has been significant progress even among high-risk patients, addressing end-of-life issues is an often neglected area,” commented briefing participant Martin A. Tallman, MD, from Memorial Sloan Kettering Cancer Center in New York City, who is also the current ASH president.

On a more upbeat note, Tallman also pointed to the results of the phase 3 randomized AGILE trial as an example of progress in AML, especially for patients with newly diagnosed high-risk disease who have mutations in isocitrate dehydrogenase 1 (IDH-1). This trial investigated a new approach to treatment, with a combination of the combination of the IDH-1 inhibitor ivosidenib (Tibsovo) and azacitidine, and compared it to azacitidine alone. The investigators assessed impact on event-free survival, overall survival, and clinical responses (abstract 697).

Tallman also highlighted abstracts touching on racial, social, and socioeconomic contributors to healthcare disparities among children with acute lymphoblastic leukemia (ALL; abstract 211) and on clinical trial enrollment characteristics and outcomes for Black and Hispanic adolescents and young adults with ALL (abstract 337).

Immunotherapy Advances

Some of the most eagerly awaited abstracts will be highlighting advances in immunotherapy for hematologic malignancies, and these were previewed by Cynthia E. Dunbar, MD, ASH secretary and chief of the Translational Stem Cell Biology Branch within the Intramural Research Program of the National Heart, Lung, and Blood Institute in Bethesda, Maryland.

These abstracts include the primary analysis of the ZUMA-7 trial, a randomized phase 3 study comparing the chimeric antigen receptor T-cell (CAR T) construct axicabtagene ciloleucel (axi-cel; Yescarta) with standard of care in patients with relapsed or refractory large B-cell lymphomas (LBCLs; abstract 2) and the interim analysis of the randomized phase 3 Transform Study comparing the CAR T construct lisocabtagene maralecleucl (liso-cel; Breyanzi) with salvage chemotherapy in patients with relapsed/refractory LBCL (abstract 91).

“Over 500 patients were enrolled in the two studies, and both abstracts report significantly longer survival without relapse in the CAR T arm ― for instance, fourfold higher in ZUMA-7 compared to standard of care,” Dunbar said at the briefing.

“These abstracts provide really critical information to patients, their treating physicians, and the payers who are trying to decide whether use of these expensive, complex, and potentially toxic CAR T-cell therapies are justified compared to standard therapy,” she said.

Dunbar also highlighted an abstract on the addition of the anti-CD38 monoclonal antibody isatuximab (Sarclisa) to lenalidomide, bortezomib, and dexamethasone as induction therapy for patients with newly diagnosed multiple myeloma who are eligible for stem cell transplantation (abstract 463).

“The authors report that patients on the isatuximab arm had significantly fewer tumor cells following treatment,” Dunbar said. “We have come a long way beyond treating myeloma with a single drug, with remissions now measured in many years instead of one or two following initiation of treatment, and this abstract is another demonstration that novel combinations of multiple agents are really making a difference in this very debilitating disease.”

She also cited an abstract (abstract 127) on monotherapy with the novel bi-specific T-cell engaging monoclonal antibody mosunetuzumab for treatment of patients with follicular lymphoma that has relapsed or is refractory to at least two prior lines of therapy.

Old Disorders, New Insights

Other abstracts highlighted at the pre-meeting press briefing included a study that found a high prevalence of monoclonal gammopathy in persons at risk for multiple myeloma (abstract 152) and another with the surprising finding that clonal hematopoiesis, a risk factor myeloid malignancies, may be protective against Alzheimer’s disease (abstract 5).

In addition, a long-term follow-up study of patients with transfusion-dependent beta-thalassemia treated with gene therapy showed that some patients have become transfusion independent and iron homeostasis was restored (abstract 573)

Presentations From CDC and FDA

Sekeres highlighted other events of interest scheduled for ASH 2021, including a Grassroots Network Lunch featuring a discussion with Rochelle Walensky, MD, MPH, director of the US Centers for Disease Control and Prevention in Atlanta, and a joint symposium between ASH and the FDA on newly approved drugs in hematology.

Sekeres has disclosed consulting/advising for Novartis, Takea/Millennium, and BMS. Dunbar reported no relevant conflicts of interest. Tallman disclosed consulting/advising with and research funding from multiple entities.

American Society for Hematology 2021 Annual Meeting: December 11–14, 2021. Georgia World Congress Center, Atlanta.

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

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