Incidence and Characteristics of Therapy-Related Myeloid Neoplasms in Patients with Non-Hodgkins Lymphoma Treated with Radioimmunotherapy

Radioimmunotherapy (RIT) delivers targeted radiation to tumor cells using cancer-specific monoclonal antibodies. Two agents, ⁹⁰Y-ibritumomab tiuxetan (Zevalin®) and ¹³¹I-tositumomab (Bexxar) have been approved for the treatment of relapsed or refractory CD20 positive low-grade, follicular, or transformed NHL. With increasing use of RIT, it is important to elucidate short and long-term toxicities of treatment, particularly the development of therapy-related myelodysplastic syndrome and/or acute myelogenous leukemia (t-MDS/AML). We are reporting on the incidence and characteristics of t-MDS/AML in 149 patients with NHL treated at a single institution.

We conducted a retrospective chart review of 149 patients with NHL treated with radioimmunotherapy at our institution. Incidences of t-MDS/AML, along with patient and disease characteristics were investigated.

149 patients with NHL were included in this analysis: All patients had received at least one cytotoxic chemotherapy regimen prior to RIT. Regimens most commonly included purine analogues, anthracyclines, alkylating agents, and topoisomerase II inhibitors. Seven out of 149 patients developed t-MDS/AML with an estimated incidence of 4. 69%, (t-MDS: 5, t-AML: 2). Five patients had follicular lymphoma, 1 with mantle cell lymphoma, and 1 with diffuse large B-cell lymphoma. Three patients received ¹³¹I-tositumomab and 4 patients received ⁹⁰Y-ibritumomab tiuxetan. The median age at RIT, and at diagnosis of t-MDS/AML, was 71. 3 and 73. 1 years respectively. The median time from RIT to diagnosis of t-MDS/AML was 1266 days (3. 47 years). The median time from initial NHL treatment to t-MDS/AML was 1680 days (4. 60 years). Two patients developed t-AML without a preceding t-MDS; one of whom had received topoisomerase II inhibitors. Six patients had cytogenetic abnormalities, with complex karyotype present in 4 patients. The majority of the karyotypic abnormalities involved chromosomes 5, 7, 11, and 20. The median time from diagnosis of t-MDS/AML to death was 278 days (0. 76 years).

Therapy –related myeloid neoplasms develop after exposure to cytotoxic agents and carry a worse prognosis than de novo disease as is shown in our series. Incidence varies according to underlying disease, specific agents received, timing of exposure, and dose. The incidence rate of 4. 69% observed in this study is within the range previously described for NHL patients treated with conventional-dose chemotherapy (Armitage J. O. et al., 2003). Most patients received fludarabine, an agent linked to a high incidence of t-MDS/AML (Carney D. A. et al., 2010). Roboz et al., 2007, noted that the median time to t-MDS/AML after standard initial therapy is approximately 6 years, which is slightly longer than our study (4. 60 years). This difference may be attributed to differences in chemotherapeutic agents utilized in that analysis for NHL therapy. T-AML without antecedent t-MDS was likely related to etoposide as has been observed in previous studies (Ratain M. J. et al., 1987, 1992). Chromosome 5 and 7 abnormalities were seen with the greatest frequency, a finding typical of t-MDS/AML (Armitage J. O. et al., 2003). This study provides an estimate of 4. 69% for the development of t-MDS/AML after NHL therapy which included chemotherapy/RIT, and suggests that RIT may not contribute to an increased risk of developing t-MDS/AML beyond what is expected with chemotherapy alone. Longer follow-up of NHL patients treated with RIT alone is necessary to determine the precise role of RIT in the development of t-MDS/AML.

No relevant conflicts of interest to declare.