Radioimmunotherapy (RIT) with ⁹⁰Y-Ibritumomab Tiuxetan (Zevalin) for the Treatment of Relapsed or Resistant Aggressive Diffuse Large B-Cell Lymphoma (DLBCL) Heavily Pretreated with Rituximab + Chemotherapy: A GIMURELL Experience.

Introduction: The addition of antibody monoclonal anti CD20 Rituximab to CHOP chemotherapy has resulted in improved CR, progression free survival and overall survival rates for patients affected by diffuse large B cell lymphoma. Recently, RIT with Zevalin has been shown effective in the treatment of relapsed refractory elderly DLBCL. We report the results of a study to evaluate the efficacy and safety of Zevalin in relapsed or chemoresistant aggressive lymphoma previously treated with Rituximab.

Patients and methods: Elegibility criteria were as follows: age over 18 years, refractory or chemoresistant CD20+ aggressive lymphoma (grade III follicular, PML or DLBCL de novo) WHO performance status of 0 to 2, stage II bulky, III or IV, bone marrow involvement < 25%, written informed consent in accordance with institutional guidelines. All patients were previously treated with Rituximab and almost two lines of chemotherapy. Patients with pre-treatment platelet counts of > 150.000/mm³ received Zevalin at 0.4 mCi/kg whereas those with platelets < 150.000/mm³ received 0.3 mCi/kg.

Results: Fourteen patients were treated with RIT: 5 patients were stage II, 3 stage III, 6 stage IV (5 with bone marrow involvement). Six patients had grade III follicular, 4 primary mediastinal and 4 DLBCL de novo. Ten patients received 0.4 mCi/kg and 4 patients 0.3 mCi/kg. Five chemoresistant patients after 2 or more lines chemoimmunotherapy received RIT in combination with BEAM and subsequent autologous stem cell transplantation (ASCT) and 9 patients were treated with Zevalin alone. Two months after RIT we reported CR 4 patients, PR 5 patients and no response/progression 5 patients (ORR 9/14 patients 64%). All 5 patients treated with RIT + BEAM + ASCT achieved a response (CR 2 patients and PR 3 patients ORR 100%). ORR in 9 patients treated with RIT alone was 46% (CR 2 patients and PR 2 patients). No toxic deaths were observed, two patients died of lymphoma (one patients 1 year after Zevalin infusion and the second progressed and died 5 months after RIT). The most common grade 3–4 AE were neutropenia and thrombocytopenia.

Discussion: RIT with ⁹⁰Y-Ibritumomab Tiuxetan is a safe and effective approach for patients affected by aggressive lymphoma and heavily pretreated with Rituximab + chemotherapy. The effective role of RIT alone or in combination with high dose chemotherapy + ASCT as salvage therapy has to be studied in this subset of patients.