Risk factors for MDS and acute leukemia following total therapy 2 and 3 for multiple myeloma

Abstract

Lenalidomide has been linked to myelodysplastic syndrome (MDS) after autotransplants for myeloma. Total therapy trials (TT; TT2(-/+) thalidomide) and TT3 (TT3a with bortezomib, thalidomide; TT3b with additional lenalidomide) offered the opportunity to examine the contribution of these immune-modulatory agents to MDS-associated cytogenetic abnormalities (MDS-CA) and clinical MDS or acute leukemia ("clinical MDS/AL"). Of 1080 patients with serial cytogenetic studies, MDS-CA occurred in 11% and clinical MDS/AL in 3%. Risk features of MDS-CA included TT3b, age ≥65 years, male gender, levels of β-2-microglobulin >5.5 mg/L, and multiple myeloma relapse. Clinical MDS/AL occurred less frequently in the control arm of TT2 and more often with TT3a and TT3b. Since MDS-CA often antedated clinical disease, periodic cytogenetic monitoring is recommended. Larger CD34 quantities should be collected upfront as the risk of MDS could be reduced by applying higher CD34 doses with transplant. Thus, treatment, host, and myeloma features could be linked to MDS development after therapy for this malignancy. This trial was registered at www.clinicaltrials.gov: TT3A: NCT00081939, TT3B: NCT00572169.

Figures

Figure 1

Cumulative incidence of MDS-CA (left panel), persistent MDS-CA (middle panel), and clinical MDS/AL (right panel), by protocol. (A) From protocol enrollment, the cumulative incidence of MDS-CA and, to a lesser degree, of clinical disease increased progressively with transition from TT2 to TT3a to TT3b. (B) From first transplantation, the cumulative incidence of MDS-CA and, to a lesser degree, of clinical disease increased progressively with transition from TT2 to TT3a to TT3b. (C) From start of maintenance therapy, the cumulative incidence of MDS-CA and, to a lesser degree, of clinical disease increased progressively with transition from TT2 to TT3a to TT3b.