A new study has found that high doses of chemotherapy combined with immunotherapy are a powerful one-two punch in treating resistant or relapsed acute myeloid leukemia (AML). While the study’s a small one, it could signal positive news.
The clinical trial, documented in the journal Blood Cancer Discovery, said that 14 of 37 patients, or 38 per cent, experienced complete remission of the highly aggressive cancer when high-dose injections of the chemo medicine cytarabine were followed by intravenous doses of pembrolizumab two weeks later. In patients who had not benefited from standard therapy, the combination of chemotherapy and immunotherapy resulted in complete remission in 46 per cent of patients who were given the therapy as their second overall treatment. With serious side effects rare and limited, the findings suggest the therapy would be an ideal treatment early in the course of AML.
Immunotherapy, a form of treatment that bolsters the body’s natural defences to better enable it to find and eliminate cancer cells, has shown promising results in clinical settings across the continent when combined with chemotherapy. “Immunotherapy has led to a paradigm shift in treating cancer but AML has lagged behind other cancers despite extensive data that it may be effective,” said Joshua Zeidner, corresponding author of the study, associate professor of medicine and chief of Leukemia Research at UNC Lineberger Comprehensive Cancer Center in North Carolina.
“Our study is the first clinical trial to investigate the role of pembrolizumab in combination with intensive chemotherapy in patients with AML that relapses or is resistant to therapy.”
At least 138,000 Canadians are living with — or are in remission from — a form of blood cancer, according to the Leukemia and Lympthoma Society. In 2017 there were over 22,000 new diagnoses in patients of all ages, with lymphoma, leukemia, myeloma and myelodysplastic syndrome constituting the bulk of cases. The number of Canadians in remission or presently fighting a form of blood cancer rose 25 per cent from 2014-2106.
The five-year survival rate for AML, a cancer that originates in stem cells in the blood, is just 21 per cent in Canada. Although this number has increased from roughly six per cent in 1975, the remaining lifespan for people with advanced forms of AML — particularly those whose cancer does not respond to aggressive treatment — is measured in months, not years.
“Overall, trial participants lived for a median of nearly one year after their therapy, which is significant in comparison to previous benefits seen from chemotherapy alone, which resulted in median survival of six to seven months,” Zeidner said.
In addition to confirming the overall efficacy of the new therapy, the study revealed that T cells — a type of cell specific to the immune system — were prevalent in patients prior to treatment. The benefits of the treatment were correlated to the function of these T cells, a finding that suggests pembrolizumab may reinvigorate T cells and that their prior presence may predict which patients will most benefit from the procedure. Different gene pathways were also present in patients that responded to pembrolizumab, meaning these genes themselves may act as biomarkers that predict efficacy.
“We hope that these study results will lead to a clinical trial of chemotherapy with or without immunotherapy,” said Jonathan S. Serody, one of the study’s senior authors and director of the Cellular Therapy Program at UNC Lineberger. “We also hope to identify robust biomarkers of response to immunotherapy that can be incorporated into future study designs.
“Additionally, we are planning to incorporate our results into a larger, multi-institutional analysis of predictive biomarkers and characteristics of response to immunotherapy in AML.”
Dave Yasvinski is a writer with Healthing.ca
For more information on blood cancers, visit the Leukemia & Lymphoma Society of Canada.