A randomized phase 3 trial of thalidomide and prednisone as maintenance therapy after ASCT in patients with MM with a quality-of-life assessment: the National Cancer Institute of Canada Clinicals Trials Group Myeloma 10 Trial

• Published in: Blood 2013-02, Vol.121 (9), p.1517-1523
• Main Authors: Stewart, A. Keith, Trudel, Suzanne, Bahlis, Nizar J., White, Darrell, Sabry, Waleed, Belch, Andrew, Reiman, Tony, Roy, Jean, Shustik, Chaim, Kovacs, Michael J., Rubinger, Morel, Cantin, Guy, Song, Kevin, Tompkins, Kirsty A., Marcellus, Deb C., Lacy, Martha Q., Sussman, Jonathan, Reece, Donna, Brundage, Michael, Harnett, Erica L., Shepherd, Lois, Chapman, Judy-Anne W., Meyer, Ralph M.
• Format: Article
• Language: English
• Subjects: Academies and Institutes; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Canada - epidemiology; Clinical Trials and Observations; Female; Hematopoietic Stem Cell Transplantation; Humans; Lymphoid Neoplasia; Maintenance Chemotherapy - methods; Male; Medical Oncology - organization & administration; Middle Aged; Multiple Myeloma - drug therapy; Multiple Myeloma - mortality; Multiple Myeloma - therapy; Prednisone - administration & dosage; Prednisone - adverse effects; Quality of Life; Survival Analysis; Thalidomide - administration & dosage; Thalidomide - adverse effects; Transplantation, Autologous; Treatment Outcome
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2012-09-451872

We conducted a randomized, controlled trial comparing thalidomide-prednisone as maintenance therapy with observation in 332 patients who had undergone autologous stem cell transplantation with melphalan 200 mg/m2. The primary end point was overall survival (OS); secondary end points were myeloma-specific progression-free survival, progression-free survival, incidence of venous thromboembolism, and health-related quality of life (HRQoL). With a median follow-up of 4.1 years, no differences in OS between thalidomide-prednisone and observation were detected (respective 4-year estimates of 68% vs 60%, respectively; hazard ratio = 0.77; P = .18); thalidomide-prednisone was associated with superior myeloma-specific progression-free survival and progression-free survival (for both outcomes, the 4-year estimates were 32% vs 14%; hazard ratio = 0.56; P < .0001) and more frequent venous thromboembolism (7.3% vs none; P = .0004). Median survival after first disease recurrence was 27.7 months with thalidomide-prednisone and 34.1 months in the observation group. Nine second malignancies were observed with thalidomide-prednisone versus 6 in the observation group. Those allocated to thalidomide-prednisone reported worse HRQoL with respect to cognitive function, dyspnea, constipation, thirst, leg swelling, numbness, dry mouth, and balance problems. We conclude that maintenance therapy with thalidomide-prednisone after autologous stem cell transplantation improves the duration of disease control, but is associated with worsening of patient-reported HRQoL and no detectable OS benefit. •Thalidomide and prednisone maintenance after transplantation improves progression-free but not overall survival.