Conference Coverage

Checkpoint inhibition after HiDAC shows promise in AML

 

Key clinical point: Adding pembrolizumab after high-dose cytarabine shows promise in relapsed/refractory AML.

Major finding: The overall response rate was 42%; 37% of patients achieved complete response or CR with incomplete blood count recovery, and 5% achieved partial response.

Study details: A multicenter, phase 2 study with early results from the first 20 patients enrolled.

Disclosures: This study was funded by Merck. Dr. Zeidner reported having no financial disclosures. The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

Source: Zeidner J et al. ALF 2018, Poster Session.


 

REPORTING FROM ALF 2018

– Adding pembrolizumab after high-dose cytarabine in patients with relapsed or refractory acute myeloid leukemia (AML) appears safe and feasible and shows promising efficacy, according to early results from a multicenter phase 2 study.

The overall response rate to this novel treatment approach in 19 evaluable patients (of 20 enrolled to date) was 42%, with 7 patients (37%) achieving a complete response or complete response with incomplete blood count recovery, and 1 (5%) achieving a partial response, reported Joshua Zeidner, MD, in a poster at the Acute Leukemia Forum of Hemedicus.

Dr. Joshua Zeidner of University of North Carolina, Chapel Hill Sharon Worcester/MDedge News

Dr. Joshua Zeidner

“Five patients went on to maintenance pembrolizumab, and – most importantly – four went to [allogeneic stem cell] transplant,” Dr. Zeidner of the Lineberger Comprehensive Cancer Center at the University of North Carolina, Chapel Hill, said in an interview.

Those who went on to allogeneic stem cell transplant included three patients in complete response and one of the five who received pembrolizumab maintenance. That patient on pembrolizumab maintenance went to transplant after two cycles, three others on it relapsed after a median duration of 2.8 months in complete response, and one initially achieved a partial response and had stable disease for a “pretty remarkable” 12 cycles before progressing, he said.

Preliminary analyses in the first six patients, including three with complete response and three nonresponders, showed increased posttreatment diversity of the T-cell receptor repertoire versus baseline in peripheral blood CD8+ T cells in the complete response patients, compared with nonresponders. This suggests that T-cell diversity at baseline is a promising biomarker for programmed death-1 (PD-1) blockade response, Dr. Zeidner noted.

PD-1 suppresses immune activation, and the PD-1 pathway is exploited by AML cells to evade immune surveillance, Dr. Zeidner explained. PD-1 blockade has been shown to have antileukemic effects in vivo, there is expression of multiple coinhibitory receptors in AML patients at the time of diagnosis (that persists in refractory AML), and the ligand for PD-1 is up-regulated on AML blasts, particularly in relapsed/refractory disease, he added.

He and his colleagues hypothesized that targeting PD-1 with pembrolizumab after high-dose cytarabine (HiDAC) salvage chemotherapy would stimulate a T cell–mediated antileukemic immune response and lead to improved efficacy in patients with relapsed or refractory AML.

Next Article:

   Comments ()

Recommended for You

News & Commentary

Quizzes from MD-IQ

Research Summaries from ClinicalEdge