Trends in risk for therapy-related myelodysplastic syndrome/acute myeloid leukemia after initial chemo/immunotherapy for common and rare lymphoid neoplasms, 2000–2018

BACKGROUND: Historically, survivors of common lymphoid neoplasms (LNs) had increased risks for therapy-related myelodysplastic syndrome/acute myeloid leukemia (tMDS/AML). Despite major treatment advances in the treatment of LNs over the last two decades, a comprehensive evaluation of tMDS/AML trends following both common and rare LNs treated in this contemporary period is lacking. METHODS: In US cancer registries during 2000–2018, we identified 1496 tMDS/AML cases among 186,503 adults who were treated with initial chemo/immunotherapy for first primary LN and survived ≥1 year. We quantified tMDS/AML standardized incidence ratios (SIRs), excess absolute risks (EARs, per 10,000 person-years), and cumulative incidence. FINDINGS: The highest tMDS/AML risks occurred after precursor leukemia/lymphoma (SIR = 39, EAR = 30), Burkitt leukemia/lymphoma (SIR = 20, EAR = 24), peripheral T-cell lymphoma (SIR = 12, EAR = 23), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL; SIR = 9.0, EAR = 27), and mantle cell lymphoma (SIR = 8.5, EAR = 25). Elevated risks (SIRs = 4.2–6.9, EARs = 4.9–15) also were observed after all other LN subtypes except hairy cell leukemia and mycosis fungoides/Sézary syndrome. Among patients treated more recently, tMDS/AML risks were significantly higher after CLL/SLL (SIR(2000-2005) = 4.8, SIR(2012-2017) = 10, P(trend) = 0.0043), significantly lower after Hodgkin (SIR(2000-2005) = 15, SIR(2012-2017) = 6.3, P(trend) = 0.024) and marginal zone (SIR(2000-2005) = 7.5, SIR(2012-2017) = 2.3, P(trend) = 0.015) lymphomas, and non-significantly lower after mantle cell lymphoma (SIR(2000-2005) = 10, SIR(2012-2017) = 3.2, P(trend) = 0.054), lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (SIR(2000-2005) = 6.9, SIR(2012-2017) = 1.0, P(trend) = 0.067), and plasma cell neoplasms (SIR(2000-2005) = 5.4, SIR(2012-2017) = 3.1, P(trend) = 0.051). EAR and cumulative incidence trends generally were similar to SIR trends. Median survival after tMDS/AML was 8.0 months (interquartile range, 3.0–22.0). INTERPRETATION: Although tMDS/AML risks are significantly elevated after initial chemo/immunotherapy for most LNs, patients treated more recently have lower tMDS/AML risks, except after CLL/SLL. Though rare, the poor prognosis following tMDS/AML emphasizes the importance of continued efforts to reduce treatment-associated toxicity. FUNDING: This research was supported in part by the Intramural Research Program of the 10.13039/100000054National Cancer Institute, National Institutes of Health. LMM, GMD, REC, and CBS verified the data, and all authors had access to the data and made the decision to submit for publication.