New Leukemia Txs, Fewer Blood Clots With GLP-1 Rxs

SAN DIEGO — Groundbreaking studies into leukemia treatments and the effects of glucagon-like peptide 1 (GLP-1) inhibitors on venous thromboembolism (VTE) risk will be presented on December 9-12 at the American Society of Hematology (ASH) 2024 Annual Meeting, according to association leaders who spoke in a media preview session. Here’s a closer look at some of the highlighted research.

Children’s Disorders: Major Progress in B-Cell Acute Lymphoblastic Leukemia (B-ALL), Immune Thrombocytopenic Purpura (ITP)

While B-ALL is the most common childhood cancer and one of the most treatable, some patients face grim outcomes after they relapse following chemotherapy, said Cynthia E. Dunbar, MD, chief of the Translational Stem Cell Biology Branch at the National Heart, Lung, and Blood Institute.

A new study reports that adding the targeted cancer drug blinatumomab (Blincyto) to chemotherapy boosted disease-free survival in standard-risk pediatric patients. “They definitively demonstrate a benefit with the addition of this immunotherapeutic drug, achieving 97% disease-free survival at 3 years on the blinatumomab plus chemotherapy arm compared to 90% for the control arm with standard therapies alone,” Dunbar said. “This trial will establish the addition of blinatumomab for childhood B-ALL as standard of care.”

A reporter asked Dunbar about the risk for severe immune activation syndrome. “These immune cell engagers can result in cytokine release syndrome and other severe immune activation consequences ,” she said. “However, it appears that children seem to be less susceptible to those, at least in terms of severity, than adults. In this study, the complications that occurred didn’t result in mortality and were easily treatable. So that was not a major drawback to the addition of this drug.”

The blinatumomab study is sponsored by Children’s Oncology Group.

In ITP, thrombopoietin (TPO) agonists such as eltrombopag (Promacta) are a mainstay of second- or third-line treatment in children and adults with severe cases, Dunbar said. “However, TPO agonists are generally only given after months to years of failures of corticosteroids, IVIG [intravenous immunoglobulin], or splenectomy.”

In the phase 3 randomized, controlled PINES trial, researchers explored whether the drug could improve outcomes in children with untreated or very recent-onset severe ITP vs standard of care.

“The children treated with eltrombopag had double the response rate with a much lower need for rescue therapies,” Dunbar said. The percentage of patients who received rescue therapy was 19% in the eltrombopag arm (15/78) vs 46% in the control arm (18/39, P = .002).

“Given the potential short- and long-term consequences of corticosteroids and other standard treatments in children, this study is encouraging and will likely result in a change in the standard of care for pediatric ITP,” Dunbar said.

The eltrombopag study is sponsored by the ITP Consortium of North America and funded by Novartis.

Fewer Blood Clots: Another Big Benefit for Weight Loss Drugs?

Mikkael A. Sekeres, MD, MS, of the Sylvester Comprehensive Cancer Center at the University of Miami, Miami, highlighted an analysis of whether GLP-1 receptor agonists, initially approved as type 2 diabetes treatments, affect the risk for VTE.

Researchers tracked patients with type 2 diabetes — 366,369 who received the drugs and 290,219 who took dipeptidyl peptidase 4 inhibitors. The patients who took GLP-1 agonists “had lower rates of venous thromboembolic events after 1 year,” Sekeres said. “The risk reduction was actually pretty substantial.”

In these patients, the risk for VTE was 18% lower (hazard ratio [HR], 0.82; 95% CI, 0.77-0.88), and there were 22% and 15% reductions in pulmonary embolisms and deep venous thrombosis, respectively (HR, 0.78; 95% CI, 0.71-0.86 and HR, 0.85; 95% CI, 0.79-0.92).

Drug Regimen Improves Outcomes in Chronic Lymphocytic Leukemia (CLL)

An interim analysis of an open-label, randomized phase 3 trial of patients with untreated CLL “demonstrated superior progression-free survival with acalabrutinib and venetoclax versus what we consider more classic chemotherapy of fludarabine, Cytoxan [cyclophosphamide], and rituximab or bendamustine and rituximab,” Sekeres said. “Similar findings were seen with acalabrutinib, venetoclax, and obinutuzumab versus that classic chemotherapy.”

Overall response rates were 93% for both the acalabrutinib/venetoclax regimens vs 75% for bendamustine/rituximab, Sekeres noted, and overall survival was higher for acalabrutinib/venetoclax vs the two classic chemotherapy regimens (HR, 0.33; P 

However, Sekeres questioned the value of comparing acalabrutinib/venetoclax with classical chemotherapy regimens. “A lot of times we have a lot of new, really good, really effective therapy to offer to patients that isn’t as toxic as previous chemotherapy.”

In contrast, fludarabine, cyclophosphamide, and rituximab are “your grandmother’s or your grandfather’s chemotherapy. It’s pretty toxic stuff,” he said.

Sekeres said it would have been better to compare acalabrutinib/venetoclax with a Bruton tyrosine kinase inhibitor-based regimen.

The German CLL Study Group is listed as the trial’s sponsor, and AstraZeneca is a collaborator.

Dunbar disclosed research funding from Novartis. Sekeres had no relevant disclosures.

Randy Dotinga is an independent writer and board member of the Association of Health Care Journalists.