Immune checkpoint inhibitors (ICIs) in combination therapy may be a promising treatment option for patients with newly-diagnosed and relapsed or refractory acute myeloid leukemia (AML), and myelodysplastic syndrome (MDS), according to a review published in Best Practice & Research Clinical Haematology.

ICIs have been used to treat solid tumor malignancies but have shown limited efficacy for AML and MDS in clinical trials; however, some early phase data have shown that checkpoint inhibitors combined with hypomethylating agents (HMAs) or intensive chemotherapy hold promise. Jan Philipp Bewerdorf, MD, and Amer M. Zeidan, MBBS, of the department of internal medicine, Section of Hematology, at Yale University School of Medicine, in New Haven, Connecticut, reviewed recent trials of combination therapies and suggested best practices for future trials.

Current Research of ICI Combination Therapies

Trials with azacitidine plus ICI showed synergistic effects of the combination therapy; however, those trials lacked a control group. One phase 2 study of ICI plus azacitidine, with the addition of durvalumab, included a control group ( Identifier: NCT02775903); the study was negative.

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The authors expressed the need for predictive biomarkers for treatment with ICI plus HMA for AML and MDS. Similarly, early phase trials of ICI with intensive chemotherapy lacked a control group. The 2 single-arm trials did not show a benefit for the addition of ICI.

Preliminary data of phase I trials evaluating ICI combinations targeting TIM-3, CD47, CD27-CD70 antibodies appeared promising; however, none of the trials had a control group. The trial evaluating the anti-CD47 antibody magrolimab had response rates of up to 100% in the MDS subpopulation but the authors urged caution in interpreting the results. Future trials may be able to use genetic testing to predict the likelihood of response for newer agents.

Suggestions for Future Trials

Based on the design and lessons learned from early phase trials, the authors suggested best practices for future trial design. Later-stage trials should have a randomized control group and clearly defined inclusion criteria. That criteria should include prior treatment history and whether patients with therapy-related myeloid neoplasms are eligible.

Future trials should also include extended follow up. The efficacy of ICI can lag behind that of conventional chemotherapy. Prolonged stable disease is more common with ICI, and the authors argued that could constitute a clinically meaningful outcome. But further follow up will be needed to determine the survival curve and to validate response criteria for ICI.

The investigators also highlighted the importance for future trials to perform molecular analyses to determine predictive biomarkers. The authors concluded that combination therapies with ICI offer promise for AML and MDS despite lackluster results in early phase trials.

Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.


Bewersdorf JP, Zeidan AM. Randomized trials with checkpoint inhibitors in acute myeloid leukaemia and myelodysplastic syndromes: What have we learned so far and where are we heading? Best Pract Res Clin Haematol. 2020;33(4):101222. doi:10.1016/j.beha.2020.101222