Despite recent advancements in FDA approved therapeutics, Acute Myeloid Leukemia (AML) remains a difficult disease to treat, with few patients experiencing long-term remission.1
In a recent paper published in Blood Advances, researchers conducted a Phase 2 trial for patients with relapsed/refractory(R/R) AML, who received a combination of azacytidine with the PD-1 checkpoint inhibitor, nivolumab.1 These patients showed promising response rates (33%) and median event-free and overall survival, compared to those treated with just azacytidine-based therapies. Furthermore, the combination azacytidine/nivolumab treatment was evaluated to have an acceptable safety profile.1
In this study, a multiplexed immune assay was used to measure the functional states of CD4+ and CD8+ T cells at a single-cell level in pretherapy bone marrow in 16 patients with R/R AML treated with azacytidine/nivolumab. The team found that effector CD4+ T cells had distinct polyfunctional groups and were associated with positive responses and better outcomes, while CD8+ T cells did not have significant polyfunctionality or drug response.1
Isoplexis’ Single-Cell Functional Phenotyping Platform Delivers Critical Predictive Metrics
AML patients treated with azacytidine in combination with nivolumab typically have short-term positive response rates, but long-term response is rare. With Isoplexis’ technology, a highly polyfunctional subset of immune cells present in AML patients were identified prior to therapy that was associated with patient response.
The team utilized single-cell functional proteomics to identify which subsets of bone marrow-infiltrating immune cells were associated with response and the specific cytokines that were driving higher polyfunctionality within this subset.
Interestingly, although response to the checkpoint blockade is believed to be determined by CD8+ T cells, IsoPlexis technology revealed that it was actually the CD4+ T cells that were inducing the response, confirming the significance of this immune cell population in favorable responses to checkpoint inhibitor therapies.
In addition, the use of IsoPlexis technology revealed that AML patients who responded to this combination therapy had distinct and highly polyfunctional subsets of CD4+ T cells prior to therapy, revealing a potential biomarker that may predict patient how a patient responds to the treatment.
“Pretreatment PSI should be evaluated in association with treatment outcomes with CTLA4, PD-L1, TIM3 and other T-cell based strategies in clinical trials in AML and may have a potential role as a biomarker in the wider sphere of immunotherapy in AML,” the authors concluded.
Treating AML is no easy feat. It is an aggressive type of cancer that requires immediate action upon diagnosis. This study highlights the power of IsoPlexis’ single-cell functional phenotyping platform, which provided a functional biomarker predictive of resultant outcomes for AML patients treated with a checkpoint inhibitor.
As the only technology that can reveal true functional insights to accelerate next-generation therapy development, Isoplexis’ platform is helping to change the outcomes of patients with AML. This study is just one example of how we are providing critical predictive metrics for the product characterization and optimization of cancer research.
Contact us today to learn how Isoplexis technology can help advance your next-generation therapies.