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Is There a Place for PD-1-PD-L Blockade in Acute Myeloid Leukemia?
Laura Jimbu1,2, Oana Mesaros1,2, Cristian Popescu1,3
1Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, 8 Babes Str., 400012 Cluj-Napoca, Romania.
Abstract:
Checkpoint inhibitors were a major breakthrough in the field of oncology. In September 2014, based on the KEYNOTE-001 study, the Food and Drug Administration (FDA) approved pembrolizumab, a programmed cell death protein 1 (PD-1) inhibitor, for advanced or unresectable melanoma. Up until now, seven PD-1/PD-ligand(L)-1 inhibitors are approved in various solid cancers and hundreds of clinical studies are currently ongoing. In hematology, PD-1 inhibitors nivolumab and pembrolizumab were approved for the treatment of relapsed/refractory (R/R) classic Hodgkin lymphoma, and later pembrolizumab was approved for R/R primary mediastinal large B-cell lymphoma. In acute myeloid leukemia (AML), the combination of hypomethylating agents and PD-1/PD-L1 inhibitors has shown promising results, worth of further investigation, while other combinations or single agent therapy have disappointing results. On the other hand, rather than in first line, these therapies could be useful in the consolidation or maintenance setting, for achieving minimal residual disease negativity. Furthermore, an interesting application could be the use of PD-1/PD-L1 inhibitors in the post allogeneic hematopoietic stem cell transplantation relapse. There are several reasons why checkpoint inhibitors are not very effective in treating AML, including the characteristics of the disease (systemic, rapidly progressive, and high tumor burden disease), low mutational burden, and dysregulation of the immune system. We here review the results of PD-1/PD-L1 inhibition in AML and discuss their potential future in the management of this disease.
Insights
Checkpoint inhibitors show promise in hematologic cancers but face challenges in acute myeloid leukemia (AML). Further research is needed to optimize PD-1/PD-L1 inhibitor use in AML treatment strategies.
Area of Science:
- Oncology
- Immunotherapy
- Hematology
Background:
- Checkpoint inhibitors, such as programmed cell death protein 1 (PD-1) inhibitors, represent a significant advancement in cancer treatment.
- PD-1/PD-L1 inhibitors are approved for various solid tumors and certain hematologic malignancies like Hodgkin lymphoma.
- Their efficacy in acute myeloid leukemia (AML) is still under investigation, with mixed results observed.
Purpose of the Study:
- To review the current outcomes of PD-1/PD-L1 inhibition in acute myeloid leukemia.
- To discuss the potential future applications and challenges of these immunotherapies in AML management.
Main Methods:
- Review of clinical studies and existing literature on PD-1/PD-L1 inhibitors in AML.
- Analysis of factors contributing to the limited efficacy of checkpoint inhibitors in AML.
- Exploration of potential therapeutic settings for PD-1/PD-L1 inhibitors in AML.
Main Results:
- Approved PD-1 inhibitors for relapsed/refractory Hodgkin lymphoma and primary mediastinal large B-cell lymphoma.
- Combination of hypomethylating agents and PD-1/PD-L1 inhibitors shows potential in AML, warranting further investigation.
- Single-agent or other combination therapies have yielded disappointing results in AML.
Conclusions:
- Checkpoint inhibitors have demonstrated success in other hematologic cancers but face significant hurdles in AML.
- Potential roles for PD-1/PD-L1 inhibitors in AML may lie in consolidation, maintenance therapy, or post-transplant relapse settings.
- Disease characteristics, low mutational burden, and immune dysregulation in AML limit the effectiveness of current checkpoint inhibitor strategies.
