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An early-stage clinical study investigating a method of boosting the body’s defenses against two blood cancers found the drug pomalidomide could be safely added to conventional treatments, and help improve immune function.

Joshua Zeidner, MD, led a phase I clinical trial investigating treatment of two blood cancers.
UNC Lineberger’s Joshua Zeidner, MD.

University of North Carolina Lineberger Comprehensive Cancer Center researcher Joshua Zeidner, MD, assistant professor in the UNC School of Medicine Division of Hematology/Oncology, led a phase I clinical trial evaluating the impact of adding pomalidomide to chemotherapy treatments for acute myeloid leukemia and myelodysplastic syndromes, or MDS. The results were published in the journal Leukemia.

They launched the study to try to reverse immune-suppressive factors that allow cancerous cells to escape the body’s defenses.

Encouraging results in phase I trial

The study involved 43 patients who were newly diagnosed with non-favorable risk acute myeloid leukemia or high-risk MDS in order to study both the safety of their strategy and the potential clinical benefits.

Patients first received chemotherapy, and then pomalidomide as their immune systems recovered from initial chemotherapy. Zeidner said the post-chemotherapy phase is a vulnerable time for patients. Researchers found in previous studies that cancer-killing immune cells are exhausted, and overpowered by the growth of other cells that suppress immune function after chemotherapy.

There were 33 patients, or 77 percent, who had a complete remission after receiving the treatment combination, Zeidner and colleagues reported, which was an improvement compared to historical rates. In a previous study, researchers reported that 68 percent of patients who did not receive pomalidomide were in complete remission after chemotherapy.

“This was higher than expected in a group of non-favorable risk patients with AML and MDS treated with conventional chemotherapy,” Zeidner said. “Moreover, we saw encouraging response rates in high-risk patients who have poor outcomes with conventional chemotherapy.”

Specifically, they saw higher remission rates high-risk subgroups compared to historical controls in patients older than 60 years, who had secondary AML, and with high-risk genetic profile.

They also found evidence that pomalidomide helped to boost immune function in patients by promoting the maturation and growth of certain cancer-killing immune cells called T-cells.

“Pomalidomide led to changes in the immune microenvironment promoting immune activation and inhibiting immune suppressive T-cell subsets,” Zeidner said. “These effects may have led to an augmented response to induction chemotherapy.”

Their work is part of an effort to find new therapeutic strategies for leukemia and for MDS.

The need for blood cancer treatment research

Standard treatment has changed very little in decades for patients with acute myeloid leukemia, Zeidner said, and often includes intensive chemotherapy for patients less than 65 years old. Less than half of AML patients see a durable remission from chemotherapy.

“Overall outcomes are unsatisfactory in patients with non-favorable risk disease, and are particularly poor in patients who have high-risk mutations, secondary AML, and high-risk MDS,” Zeidner said. “Novel agents are urgently needed to improve outcomes in these subgroups of patients with AML and MDS.”

Based on the study’s findings, UNC Lineberger researchers are preparing to launch a phase II study of chemotherapy with or without pomalidomide in patients with high-risk AML. Their primary objective will be to see whether they can improve responses and overall outcomes of standard intensive chemotherapy.

“One of the highest unmet needs in AML is finding effective therapies for patients with adverse-risk disease, as our chemotherapy agents are largely ineffective for these patient populations,” he said. “Therapies targeting the immune system have great promise for these patients with chemo-resistant disease. We hope that future studies will identify which patients respond best to to immune-based approaches in the context of intensive chemotherapy and other combinations.”

Authors and Disclosures

In addition to Zeidner, other authors included: Hanna A. Knaus, Amer M. Zeidan, Amanda L. Blackford, Raul Montiel-Esparza, Hubert Hackl, Gabrielle T. Prince, Lukasz P. Gondek, Gabriel Ghiaur, Margaret M. Showel, Amy E. DeZern, Keith W. Pratz, B. Douglas Smith, Mark J. Levis, Steven Gore, Catherine C. Coombs, Matthew C. Foster, Howard Streicher, Judith E. Karp, Leo Luznik and Ivana Gojo.

The study was supported by National Cancer Institute grants to Johns Hopkins, University of North Carolina and Yale University. Individual researchers were supported by a Leukemia and Lymphoma Society Special Fellow in Clinical Research Award, the ASBMT New Investigator Award/Gabrielle’s Angel Foundation, the Vienna Fund for Innovative Cancer Research, the Leukemia and Lymphoma Society Scholar in Clinical Research award, and a NCI Clinical Investigator Team Leadership Award. 

Conflicts of interest: Zeidner has received research funding from Celgene, Merck, Takeda and Tolero Pharmaceuticals, honoraria from AbbVie, Agios, Celgene, Daiichi Sankyo, Genentech, Pfizer, and Tolero Pharmaceuticals, and has served as a consultant for AsystBio Laboratories, Celgene, Covance and Takeda. View disclosures for all authors.