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Sneak Peek at Practice-Changing Research From ASH 2018

— "Big trials, big results," plus sickle cell disease and CAR T-cell therapies

Last Updated December 4, 2018
MedpageToday

SAN DIEGO -- The largest and top conference for hematologists and blood disease specialists is just about underway here.

While pre-conference activities at the 60th American Society of Hematology (ASH) Annual Meeting -- industry-sponsored symposia and ASH-a-Palooza (formerly Trainee Day) -- are taking place on Friday, ASH 2018 officially starts early Saturday morning when the scientific program kicks off with simultaneous oral and educational sessions, followed by the first of the poster displays.

An estimated 25,000 people from 115 countries are expected to attend the 4-day conference.

"It's really shaping up to be a very exciting meeting," said Aaron Gerds, MD, MS, of the Cleveland Clinic in Ohio and chair of the ASH Committee on Communications, during a press briefing ahead of the meeting. "I know we say this every year, but I anticipate this will be the best annual meeting ever."

Mark your calendar for an early evening talk with National Cancer Institute (NCI) Director Norman E. Sharpless, MD, who will discuss his vision of big data, workforce development, and basic science at the NCI.

Sunday's plenary session will feature six studies of the "highest caliber," selected from nearly 5,000 abstracts covering the latest research on the biology and treatment of hematologic malignancies, blood dyscrasias, clotting disorders, sickle cell anemia, and other diseases and disorders of the blood.

Also on the agenda during the meeting are two afternoon sessions covering new ASH guidelines. On Sunday, attendees can get a preview of the 2019 sickle cell disease guidelines, and on Monday, authors of the just-released venous thromboembolism guidelines will discuss their recommendations.

Monday will also feature a pair of joint symposia from ASH and the FDA on recently approved drugs for hematological disorders.

Key themes and topics at the meeting will be "Big Trials, Big Results," as the meeting organizers put it, along with sickle cell disease, CAR T-cell therapies, and the future of medicine -- a window into what treatment in hematology may look like in the years ahead.

Big Trials, Big Results

The FLYER trial (), a de-escalation study in diffuse large B-cell lymphoma (DLBCL) patients with favorable prognosis, topped the list for the "Big Trials, Big Results" theme.

"This is almost certainly going to be practice changing," said ASH Secretary Robert A. Brodsky, MD, of Johns Hopkins School of Medicine in Baltimore, during the press briefing.

Another practice changer (), he said, compared ibrutinib (Imbruvica) alone or with rituximab (Rituxan) to chemoimmunotherapy in untreated, older chronic lymphocytic leukemia (CLL) patients.

"The reason this is important is ibrutinib has been FDA approved for untreated CLL since 2016, but here it's been compared to chlorambucil, which is not a very effective therapy," he explained. "The critique of this is it's never been compared against what we would consider a modern standard of care for CLL."

Sickle Cell Disease

One of the studies highlighted by ASH President Alexis Thompson, MD, MPH, of the Robert H. Lurie Children's Hospital of Chicago, reports 2-year outcomes for high-risk sickle cell disease patients who underwent familial haploidentical stem cell transplantation. The researchers found improved quality of life and neurocognition ().

"This is actually a really interesting study," said Thompson, noting that the researchers looked at various outcomes including cardiovascular disease, neurocognitive deficits, processing speed, and emotional and physical functioning.

Another study () examined opioid use and mortality for sickle cell disease patients, who often require high doses. "There does not appear to be an increased association of in-hospital mortality in patients with sickle cell compared to the general population," she said.

As opioid-related deaths in the U.S. climbed from 1999 to 2013, the researchers found that in-hospital mortality among those with sickle cell disease remained steady. Thompson said the findings should alleviate many concerns about opioid use in these patients.

CAR T-Cell Therapies

"CAR T cells continue to play a prominent role in the management of refractory B-cell malignancies," said Brodsky.

He pointed to two studies that aimed to reduce toxicity or improve the efficacy of CAR T-cell therapy in relapsed or refractory CLL and B-cell acute lymphoblastic leukemia (ALL). The CLL trial (), which he cautioned had just 36 patients, combined CD19-specific CAR T cells with ibrutinib.

"This was well tolerated, and there's a suggestion at least that the ibrutinib was able to decrease some of the side effects -- the cytokine release that is often seen with CAR T-cell therapy -- and there may even be evidence that this can actually improve response," he said. "Early, preliminary, but very exciting."

In ALL, the checkpoint inhibitor pembrolizumab (Keytruda) was combined with CAR T cells with the goal of preventing relapse and seemed to show benefit in half the patients ().

Late-Breaking Abstracts

Among the late breakers is a trial of emapalumab (Gamifant) for primary hemophagocytic lymphohistiocytosis (HLH), which led to FDA approval earlier this month in this setting, the first agent cleared by the agency specifically for HLH.

"Suffice it to say that this drug was very effective in controlling the disease," Brodsky said. "This is going to have a major impact."

A phase III study of daratumumab (Darzalex) in newly diagnosed myeloma patients who are ineligible for transplant will be another to watch for. Asked whether the agent may have an advantage over current available first-line therapies in myeloma, Brodsky said that this would be one of the takeaways from the meeting, noting that daratumumab is giving patients deeper responses, longer remissions, and looks to be offering better survival as well.

Other late-breaking abstracts include a look at rivaroxaban thromboprophylaxis in high-risk ambulatory cancer patients on systemic therapy; a phase III trial comparing first-line ibrutinib against chemoimmunotherapy in younger CLL patients; findings on a BCL2 mutation that confers resistance to venetoclax (Venclexta) in progressive CLL; and results of the PAUSE study of perioperative management for patients with atrial fibrillation on direct oral anticoagulants.