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

• Published in: Blood 2013-06, Vol.121 (23), p.4753-4757
• Main Authors: Usmani, Saad Z., Sawyer, Jeffrey, Rosenthal, Adam, Cottler-Fox, Michele, Epstein, Joshua, Yaccoby, Shmuel, Sexton, Rachael, Hoering, Antje, Singh, Zeba, Heuck, Christoph J., Waheed, Sarah, Chauhan, Nabeel, Johann, Donald, Abdallah, Al-Ola, Muzaffar, Jameel, Petty, Nathan, Bailey, Clyde, Crowley, John, van Rhee, Frits, Barlogie, Bart
• Format: Article
• Language: English
• Subjects: Acute Disease; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Boronic Acids - administration & dosage; Bortezomib; Brief Report; Chromosome Aberrations; Female; Follow-Up Studies; Humans; Incidence; Lenalidomide; Leukemia - chemically induced; Leukemia - epidemiology; Leukemia - genetics; Lymphoid Neoplasia; Male; Middle Aged; Multiple Myeloma - complications; Multiple Myeloma - drug therapy; Myelodysplastic Syndromes - chemically induced; Myelodysplastic Syndromes - epidemiology; Myelodysplastic Syndromes - genetics; Neoplasm Recurrence, Local - chemically induced; Neoplasm Recurrence, Local - epidemiology; Neoplasm Recurrence, Local - genetics; Prognosis; Pyrazines - administration & dosage; Risk Factors; Thalidomide - administration & dosage; Thalidomide - analogs & derivatives; Young Adult
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2012-11-466961

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. •MDS-CAs were observed in 11% of 1080 patients and often preceded clinical MDS/acute leukemia.•Risk factors for MDS-type cytogenetic abnormalities included immuno-modulatory drugs, older age, male gender, and low CD34 dose (