Successfully treated cancer patients may have high risk of developing secondary malignancies
Cancer patients who have undergone successful treatment may have increased risk of developing therapy-related myeloid neoplasms (t-MNs), a fatal form of secondary malignancy, even after years of successful treatment, according to a recent study presented at the ASH 58th Annual Meeting in San Diego, California, US.
“In most cases, it is fatal, and currently, there is no way to predict who is at risk, or to prevent it,” said study co-author Dr Andy Futreal from the Department of Genomic Medicine at The University of Texas MD Anderson Cancer Center in Houston, Texas, US, who noted that t-MNs occurs in about 5 percent of cancer patients who have undergone radiation therapy and/or chemotherapy.
Targeted capture sequencing (median depth 245x) was performed on bone marrow (BM) and peripheral blood (PB) samples from 14 patients with t-MNs, whose samples were obtained at the time of diagnosis and pretherapy. A control cohort of 54 patients with lymphoma who did not develop t-MNs post-therapy and a validation cohort of 74 patients with lymphoma who received CHOP*-based chemotherapy were also included for further investigation.
Among the 14 cases with t-MNs, traces of clonal hematopoiesis, a genetic preleukaemic mutation that may increase the risk of developing t-MNs, were identified in 10 samples (71 percent).
In the control cohort, traces of clonal hematopoiesis were identified in 17 samples (31 percent), suggesting that patients with t-MNs had a higher incidence of the mutation (71 percent vs 31 percent; p=0.008). The rate of development of t-MNs at 5 years was significantly higher in patients with clonal hematopoiesis than in patients without (30 percent, 95 percent CI, 16–51 percent vs 7 percent, 95 percent CI, 2–21 percent; p=0.015).
Among patients in the validation cohort, clonal hematopoiesis was identified in four of five patients (80 percent) who developed t-MNs, and in 11 of 69 patients (16 percent) who did not develop t-MNs. The rate of development of t-MNs at 10 years was significantly higher in patients with clonal hematopoiesis than in patients without (29 percent, 95 percent CI, 12–59 percent vs 0 percent, 95 percent CI, 0–0 percent; p=0.001).
Identifying preleukaemic mutations increased the risk of developing t-MNs in both control and validation studies, the authors noted. These finding suggest that preleukaemic mutations may serve as a predictive biomarker in the development of t-MNs and may aid in cancer screening measures to help identify patients at risk of developing t-MNs.
Early detection is critical as t-MNs can manifest even after 3 to 8 years postradiation therapy and/or chemotherapy. These findings warrant further investigation into the role of preleukaemic mutations as a predictive biomarker for t-MNs, according to the authors.
“Since many cancer patients are now living longer, t-MNs are an increasing concern for many cancer survivors,” said study co-author Dr Koichi Takashi from the Department of Leukemia at The University of Texas MD Anderson Cancer Center in Houston, Texas, US.