Why older patients do more poorly isn’t known, but a new study by researchers at the Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute indicates that some older acute leukemia patients whose cancer cells have mutations in a gene called NPM1 respond better to therapy and experience longer survival.
Currently, mutations in this gene are known to signal a favorable prognosis in younger patients with acute myeloid leukemia (AML). The findings of this study indicate that the same is true for older patients, and it suggests that these older patients should perhaps be offered stronger therapy, the researchers say.
“These findings were completely unexpected,” says study leader Dr. Clara D. Bloomfield, Distinguished University Professor and Ohio State University Cancer Scholar. “Even patients over age 70 who have NPM1 mutations do better than those with the normal gene. This study supports the importance of understanding and thinking positively about what we can do for older people with leukemia,” she says.
The findings are reported online Dec. 21 in the Journal of Clinical Oncology.
Bloomfield and her colleagues examined the outcomes of 148 AML patients age 60 and older whose cancer cells have normal-looking chromosomes. That is, they have normal cytogenetics, a feature seen in more than half of adults with AML. All the patients had been treated through one of two national clinical trials sponsored by the Cancer and Leukemia Group B (CALGB), a clinical cooperative group.
Overall, 83 patients (56 percent) had NMP1 mutations. Of these, 84 percent had a complete remission (a necessary event for long-term survival or cure) compared with 48 percent of patients whose cancer cells had a normal NPM1 gene.
Patients with the mutated gene also had a significantly higher three-year survival rate: 35 percent compared with 8 percent.
Of 31 patients age 70 and older with the mutated gene, 27 (87 percent) had a complete remission, compared with 15 of 38 patients (39 percent) with a normal NPM1 gene. The difference in overall survival was even more striking: 45 percent of patients over age 70 with NPM1 mutations were alive after three years compared with 5 percent of those with the normal gene.
The study also showed few overall genetic or molecular differences in the leukemic cells between older and young patients, suggesting that cytogenetically normal AML with NPM1 mutations is the same disease entity in both age groups.
“The overall favorable treatment response of patients with NPM1 mutations suggests that these mutations may represent a marker that can be used to stratify older patients with cytogenetically normal AML to intensive chemotherapy, which is often avoided in older patients because of disappointing clinical results,” says coauthor Dr. Guido Marcucci, associate professor of medicine and an AML specialist at the James Cancer Hospital and Solove Research Institute.
Funding from the National Cancer Institute, the Coleman Leukemia Research Foundation, and the Deutsche Krebshilfe-Dr. Mildred Scheel Cancer Foundation supported this research.
Other Ohio State researchers involved in this study were Heiko Becker, Kati Maharry, Michael D. Radmacher, Krzysztof Mrózek, Dean Margeson, Susan P. Whitman, Yue-Zhong Wu, Sebastian Schwind, Peter Paschka and Michael A. Caligiuri.
The Ohio State University Comprehensive Cancer Center- Arthur G. James Cancer Hospital and Richard J. Solove Research Institute is one of only 40 Comprehensive Cancer Centers in the United States designated by the National Cancer Institute. Ranked by U.S. News & World Report among the top 20 cancer hospitals in the nation, The James (www.jamesline.com) is the 180-bed adult patient-care component of the cancer program at The Ohio State University. The OSUCCC-James is one of only five centers in the country approved by the NCI to conduct both Phase I and Phase II clinical trials.