Clinical Characteristics and Prognosis of Secondary Acute Lymphoblastic Leukemia in Patients with Multiple Myeloma during Long-Term Thalidomide Maintenance

Background: Secondary primary malignancies (SPM) have attracted increasing attention with the application of autologous hematopoietic stem cell transplantation (ASCT) and novel agents in multiple myeloma (MM). Secondary acute lymphoblastic leukemia (sALL) has rarely been reported, and the clinical characteristics and prognosis of sALL have not been described in detail. Methods: We retrospectively enrolled 179 consecutive newly diagnosed multiple myeloma (NDMM) patients undergoing bortezomib-based induction regimens followed by upfront ASCT and maintenance therapy from December 2006 to April 2018 in our center. Results: The median follow-up interval was 69.1 months, and 12 patients (6.7%) developed sALL during maintenance therapy. The median time from the diagnosis of MM to the occurrence of sALL was 51.1 (31.7–91.5) months. All sALL patients received thalidomide as maintenance therapy before the onset of sALL, and the median duration of thalidomide maintenance was 39.5 (24–74) months. The cumulative incidence of sALL was 6.6% and 11.2% at 5 and 10 years after the diagnosis of MM, respectively. All sALL patients presented with a B-cell immunophenotype accompanied by myeloid antigen expression according to flow cytometry analysis, and the BCR/ABL fusion gene was all negative. Only one patient had evidence of active MM, and the other patients were in stable status at the time of the diagnosis of sALL. The prognosis of most sALL patients was very poor, and the median overall survival time was 11.9 (1.1–51.2) months since the diagnosis of sALL. Conclusions: sALL should be considered for MM patients who developed unexplained persistent cytopenia while on long-term thalidomide maintenance treatment, particularly if it has been more than 3 years. With the increasing availability of new drugs for MM, thalidomide may be recommended for no more than 3 years. Sequential allogeneic hematopoietic stem cell transplantation was considered as soon as possible after achieving remission in order to achieve a longer survival.