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A Randomized Phase II Study Comparing Consolidation With a Single Dose Of 90y Ibritumomab Tiuxetan (Zevalin®) (Z) Vs. Maintenance With Rituximab (R) For Two Years In Patients With Newly Diagnosed Follicular Lymphoma (FL) Responding To R-CHOP. Preliminary Results At 36 Months From Randomization

2013; Elsevier BV; Volume: 122; Issue: 21 Linguagem: Inglês

10.1182/blood.v122.21.369.369

1528-0020

Armando López‐Guillermo, Miguel Canales, Iván Dlouhy, Javier Briones, Dolores Caballero, Juan‐Manuel Sancho, Santiago Mercadal Vilchez, José M. Moraleda, María José Terol, Antonio Salar, Luis Palomera, Santiago Gardella, Isidro Jarque, Secundino Ferrer, Joan Bargay, Andrés López, Carlos Panizo, A. Muntañola, Carlos Montalbán, Eulogio Conde, Miguel‐Teodoro Hernández, A. Soler, Julián Marín, Jose García Marco, Guillermo Debén, José Francisco Tomás,

Chronic Lymphocytic Leukemia Research

Abstract Patients with FL can have long time of survival, but disease progression typically occurs 3-5 years after initial treatment. Consolidation with Z after initial therapy has shown to improve progression-free survival (PFS) mainly in the pre-R era, whereas maintenance with R also has demonstrated a substantial benefit in terms of PFS in patients treated with immunochemotherapy. In this setting, the Spanish intergroup PETHEMA/GELTAMO/GELCAB started a randomized phase 2 trial in order to compare the use of consolidation with Z vs. R maintenance in patients with FL responding to R-CHOP. From June 2008 to July 2010, 146 patients (66M/80F; median age, 55 years) were enrolled from 25 Spanish institutions in the randomized phase 2 trial ZAR2007 (ClinicalTrials.gov, number NCT00662948). Main inclusion criteria were: FL grade 1, 2 or 3a, age 18-75 years, stages II-IV and need of treatment according to modified GELF criteria. Patients with FL grade 3b or transformed to DLBCL were excluded. In addition, patients with platelet count <150x109/L or bone marrow infiltration>25% before randomization were also excluded. Main end-point of the trial was PFS from randomization. The distribution according to the FLIPI score was as follows: low-risk 14%, intermediate 47%, and high 39%. After R-CHOP, 124 patients in CR (n=56), CR[u] (13) or PR (55) were randomized 1:1 (stratified by response) to arm A (90Y ibritumomab tiuxetan 0.4 mCi/kg IV; total dose of 90Y was capped at 32 mCi) vs. arm B (1 infusion of R 375 mg/m2 every 8 weeks for 2 years). Sixty three (51%) patients were assigned to arm A (Z) and 61 (49%) to arm B (R). Twenty two patients were not randomized due to response <PR, low neutrophil or platelets counts or patient decision. After a median follow-up of 37 months from randomization (range, 26 to 56), 31 patients eventually progressed/relapsed with a 36-month PFS of 64% (95% confidence interval [CI] 52-76) for patients in arm A (consolidation with Z) (22 events) and 86% (95% CI 77-95) for patients in the R maintenance (9 events) (p=0.01; HR=0.38, 95%CI 0.17-0.83) as shown in the figure. The number of patients in PR after R-CHOP who reached CR during maintenance were 14 of 28 (50%) and 12 of 26 (46%) for arms A and B, respectively. Two patients developed transformation to DLBCL at 8 (arm A) and 39 months (arm B) after randomization. During the maintenance period, patients receiving Z showed grade 3-4 neutropenia in 6 of 63 cases and grade 3-4 thrombocytopenia in 5 of 63, whereas these figures were 1 of 61 and 0 of 61 (p=0.05) for patients in arm B, respectively. No unexpected late toxicities have been reported. Five patients have died during the follow-up due to the progression of lymphoma in all cases, with no differences between the arms (36-month OS, 98% vs. 95% for arms A and B, respectively). In conclusion, in patients with FL in response after R-CHOP, maintenance with R was superior to consolidation with Z in terms of PFS, with no differences in OS with the current follow-up. Disclosures: Lopez-Guillermo: Roche: Membership on an entity’s Board of Directors or advisory committees. Briones:F. Hoffmann-La Roche: Honoraria.