ASH Clinical News January 2016 | Page 36

Literature Scan New and noteworthy research from the medical literature landscape Meta-Analysis of Maintenance Therapy in Multiple Myeloma: Time to Rethink Immunomodulatory-Based Maintenance Therapy? Maintenance therapy with immunomodulatory drugs (IMiDs; including thalidomide, lenalidomide, and pomalidomide) and the proteasome inhibitors bortezomib and carfilzomib has been shown to increase event-free and progression-free survival (PFS) in patients with multiple myeloma (MM), but questions about their efficacy in extending overall survival and the safety of long-term use remain. In a recent meta-analysis published in the Journal of the National Cancer Institute, Yucai Wang and colleagues from the Department of Medicine at Rutgers New Jersey Medical School in Newark, New Jersey, examined randomized controlled trials (RCTs) that studied the safety and efficacy of thalidomide and lenalidomide as maintenance therapy for patients with MM, with the goal of establishing the best algorithms for MM management. Dr. Wang and co-authors searched PubMed and abstract databases for major hematology/ oncology meetings to identify 18 phase III RCTs, enrolling a total of “IMiD-based maintenance therapy can significantly improve PFS but not OS in MM , regardless of AutoHCT status.” —YUCAI WANG 34 ASH Clinical News Effects of IMiD-Based Maintenance Therapy on Progression-Free and Overall Survival TABLE 1. IMiD Thalidomide/ lenalidomide Thalidomide Lenalidomide Overall survival Number of trials HR (95% CI) p Value HR (95% CI) p Value Combined 18 0.62 (0.57-0.67) <0.001 0.93 (0.85-1.01) 0.082 With AutoHCT 9 0.61 (0.54-0.68) <0.001 0.89 (0.73-1.07) 0.214 Without AutoHCT 11 0.63 (0.55-0.71) <0.001 0.95 (0.88-1.04) 0.273 Combined 12 0.66 (0.61-0.72) <0.001 0.94 (0.85-1.05) 0.278 With AutoHCT 6 0.67 (0.61-0.74) <0.001 0.90 (0.73-1.11) 0.343 Without AutoHCT 7 0.66 (0.57-0.76) <0.001 0.97 (0.85-1.11) 0.627 Combined 6 0.52 (0.44-0.62) <0.001 0.87 (0.73-1.04) 0.135 With AutoHCT 3 0.49 (0.41-0.57) <0.001 0.82 (0.48-1.41) 0.477 Without AutoHCT 4 0.55 (0.43-0.72) <0.001 0.95 (0.85-1.05) 0.308 7,730 patients. Among these trials, IMiDs used in the maintenance therapy regimen included thalidomide (12 trials) and lenalidomide (6 trials). IMiD-based maintenance therapy was used after patients received autologous hematopoietic cell transplantation (AutoHCT) in seven trials, and nine trials evaluated the safety and efficacy of maintenance therapy in the nontransplant setting. Two trials had enrolled both transplant-eligible and -ineligible patients. Overall, IMiD-based maintenance therapy statistically significantly improved the PFS (hazard ratio [HR] = 0.62; 95% TABLE 2. Progression-free survival AutoHCT status CI 0.57-0.67; p<0.001) in patients with MM (TABLE 1). In subgroup analyses, both thalidomide- and lenalidomide-containing regimens improved PFS. “[For thalidomide] the PFS prolongation was observed in all six studies (HR=0.56-0.73), demonstrating an unequivocal benefit of thalidomide maintenance therapy after AutoHCT in delaying disease progression,” Dr. Wang and colleagues noted. This improvement was also seen in both transplant and non-transplant settings: HR=0.61 (95% CI 0.54-0.68; p<0.001) and HR=0.63 (95% CI 0.55-0.71; p<0.001), respectively. Conversely, IMiD-based maintenance therapy was not associated with a statistically significant improvement in overall survival (OS), though there was a trend for longer OS: HR=0.93 (95% CI 0.85-1.01; p=0.082). This was true regardless of the type of IMiD used or transplant eligibility: • Thalidomide: HR=0.94 (95% CI 0.85-1.05; p=0.278) • Lenalidomide: HR=0.87 (95% CI 0.73-1.04; p=0.135) • Transplantation: HR=0.89 (95% CI 0.73-1.07; p=0.214) Grade 3 or 4 Adverse Even ts Adverse event Number of trials Events in IMiD arm Risk ratio (95% CI) p Value Vascular events 10 123/1,958 2.52 (1.41-4.52) 0.002 Peripheral neuropathy 6 53/1,419 2.27 (1.35-3.84) 0.002 Neutropenia 9 484/1,894 2.73 (1.63-4.55) <0.001 Thrombocytopenia 10 159/1,886 2.14 (1.34-3.40) 0.001 Anemia 10 149/1,955 1.43 (1.13-1.80) 0.003 Infection 9 297/1,654 1.64 (1.40-1.92) <0.001 Fatigue 10 130/1,969 1.48 (1.08-2.03) 0.016 Constipation 7 36/1,502 1.82 (1.03-3.21) 0.039 Second primary malignancies 7 93/1,593 1.33 (0.81-2.19) 0.257 January 2016