Study Finds Elevated Risk of MDS and AML After Chemotherapy for Most Solid Tumors
Findings from a new study by researchers at the National Cancer Institute (NCI) show that patients treated with chemotherapy for most solid tumors from 2000 to 2014 experienced an increased risk of therapy-related myelodysplastic syndrome/acute myeloid leukemia (MDS/AML). The study, which used U.S. population-based cancer registry data from NCI’s Surveillance, Epidemiology, and End Results (SEER) program and treatment information from the SEER–Medicare database, was published by Morton et al in JAMA Oncology.
“We’ve known for a long time that the development of myeloid leukemia is a very rare adverse effect of some types of cancer treatments that damage cells,” said Lindsay Morton, PhD, lead author of the study and a senior investigator in NCI’s Division of Cancer Epidemiology and Genetics. “There have been many changes in cancer treatment over time, including the introduction of new chemotherapy drugs and drug combinations, but we didn’t know what the risk of therapy-related leukemia looked like for patients since these changes were made.”
Because therapy-related MDS/AML is rare, most data on the disease have come from case series, case-control studies, and clinical trials, which often include a relatively small number of therapy-related MDS/AML cases.
Study Methods
In this study, researchers analyzed SEER registry data on more than 700,000 patients aged 20–84 in the United States with solid tumors who were diagnosed and treated with initial chemotherapy during 2000–2013 and survived at least 1 year after diagnosis.
Findings
Of these patients, 1,619 developed therapy-related MDS/AML through 2014. When the researchers analyzed the risk of therapy-related MDS/AML by original cancer type, they found that risk was increased by 1.5-fold to more than 10-fold for 22 of the 23 solid cancer types investigated (all except colon cancer).
These findings expand the groups of survivors at risk of therapy-related MDS/AML following treatment with chemotherapy because, in the past, excess risks were established only after chemotherapy for cancers of the lung, ovary, breast, soft tissue, testis, and brain/central nervous system. In the present analysis, cumulative incidence of therapy-related MDS/AML was less than 1% at 10 years after chemotherapy for most solid cancer types. However, prognosis following therapy-related MDS/AML diagnosis was poor—1,270 of 1,619 patients (78.4%) died, and their median overall survival was 7 months. For patients treated with chemotherapy at the present time, approximately three-quarters of therapy-related MDS/AML cases expected to occur within the next 5 years will be attributable to chemotherapy.
Because information on the specific chemotherapy agents was not available in the SEER registry data, the researchers used the SEER–Medicare linked database to examine the patterns of use of specific chemotherapy agents during the same time period. Among 165,000 patients in the SEER–Medicare database who received initial chemotherapy for a first primary solid cancer during the study period, 2000–2013, there was a substantial rise in use of platinum-based chemotherapy agents, from 57% of patients in 2000–2001 to 81% of patients in 2012–2013. Platinum-based chemotherapy agents are known to increase risk of therapy-related MDS/AML.
“The most important message from this study is that, while advances in cancer treatment approaches have improved the prognosis for many types of cancer, the number of patients at risk of developing rare, therapy-related leukemia after cancer chemotherapy in the modern treatment era has markedly expanded,” Dr. Morton said. “Assessments of treatment risks and benefits should balance these risks and other adverse effects of chemotherapy against potential gains in survival following treatment for the initial solid cancer.”
The researchers wrote that their study shows that continued efforts to minimize exposure to leukemia-causing chemotherapy agents and to develop effective and less toxic chemotherapeutic approaches are critical going forward.
Disclosure: The study authors’ full disclosures can be found at jamanetwork.com.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
