Effect of Prognostic Risk Classification on Temsirolimus Efficacy and Safety Outcomes in Patients with Relapsed/Refractory Mantle Cell Lymphoma (2011)

Abstract Abstract 2708 Background: The simplified Mantle Cell Lymphoma International Prognostic Index (MIPI) has been shown to be a good predictor of patient survival (Blood 2008;111:558–65; Blood 2010;115:1530–1533). This post hoc study analyzed data from a randomized, phase III clinical trial investigating temsirolimus (TEM) in relapsed/refractory mantle cell lymphoma (MCL) in which TEM 175/75 (175 mg for first 3 weeks then 75 mg weekly) demonstrated significantly longer progression-free survival (PFS) vs investigator's choice of therapy (INV; 4.8 vs 1.9 months, respectively; hazard ratio [HR]=0.44; P=.0009; J Clin Oncol 2009;27:3822–9). Patients receiving TEM 175/25 (175 mg for first 3 weeks then 25 mg weekly) also had longer PFS vs INV, but this difference was not significant (3.4 vs 1.9 months; respectively; HR=0.65; P=.06). During the trial, baseline prognostic risk classification was not recorded; thus, patients were retrospectively assigned baseline prognostic scores, and outcomes were analyzed according to risk category. Methods: All patients (N=162) were classified as low, intermediate, or high risk using the simplified MIPI. The MIPI scores were based on 4 independent prognostic markers: age, Eastern Cooperative Oncology Group (ECOG) performance status, lactate dehydrogenase level, and white blood cell count. Median PFS and overall survival (OS) were calculated using Kaplan-Meier estimates, and treatment effect was assessed using log-rank statistics. P values of ≤.05 indicated significance of the treatment effect between the 2 treatment groups. As the phase III study was not powered to analyze patients according to MIPI risk categorization, statistical analyses shown are for explanatory purposes. Results: Distribution was relatively even across MIPI risk categories (55 patients low, 59 patients intermediate, 48 patients high). MIPI distributions in the 2 TEM arms were: 175/75 (n=54: 28% low, 43% intermediate, 30% high); 175/25 (n=54: 28% low, 33% intermediate, 39% high). Relative to the TEM arms, the INV arm (n=54) had a higher proportion of low-risk patients (46% low; 33% intermediate; 20% high). TEM 175/75 resulted in significant improvement in median PFS (independent assessment) vs INV in high-risk patients (P=.003) (Table); trends toward improvement were observed for intermediate-risk and low-risk patients (P=.06 in each group). By investigator assessment, TEM 175/75 improved median PFS vs INV by 7.9 months in the low-risk category (P=.0007) and by 2.8 months (P=.06) and 1.1 month (P=.001) in the intermediate-risk and high-risk categories, respectively. A trend toward longer OS was observed in the low-risk patients treated with TEM 175/75 vs INV (P=.0502). In the low-risk category, maintenance of stable disease or better response was achieved in more patients receiving TEM 175/75 (9/15 [60%]) vs INV (5/25 [20%]); objective responses were observed in 5 patients with TEM 175/75 and in no patients with INV. Patients in the low-risk category treated with TEM 175/75 received a longer duration of therapy vs INV (30.7 vs 9.0 wk, respectively). Across the duration of treatment, the average frequency of delay was once per 5.6 wk with TEM 175/75 vs once per 6.4 wk with INV. TEM was generally well tolerated. Grade 3/4 anemia, thrombocytopenia, and infection also were analyzed by patient risk category. In both the TEM 175/75 and INV groups, the selected grade 3/4 events occurred more commonly in high-risk than low-risk patients. In the low-risk category, a higher incidence of grade 3/4 thrombocytopenia and anemia was observed with TEM 175/75 vs INV. Conclusions: Retrospective risk analysis of patients according to the simplified MIPI demonstrated that TEM 175/75 was effective across patient risk categories. The greatest benefit trend was observed in low-risk patients. In this study of relapsed/refractory MCL patients, MIPI was a good predictor of survival outcome. Disclosures: Hess: Pfizer: Consultancy, Honoraria, Research Funding. Off Label Use: Torisel is licensed for treatment of relapsed and/or refractory mantle cell lymphoma and renal cell carcinoma in Europe. Torisel is licensed in the US for renal cell carcinoma. Kang:Pfizer: Employment. Moran:Pfizer: Employment.