Radioimmunotherapy (RIT) with 90y-Ibritumomab Tiuxetan (Zevalin) in Relapsed or Refractory Aggressive Lymphoma Previously Treated with Rituximab Containing Regimens
Authors: Botto Barbara , Bellò Marilena , Chiappella Annalisa , Passera Roberto , Benevolo Giulia , Boccomini Carola , Cabras Maria Giuseppina , Castellino Claudia , Fioritoni Giuseppe , Frairia Chiara , Freilone Roberto , Martelli Maurizio , Orsucci Lorella , Pregno Patrizia , Scapoli Paola , Tonso Anna , Ricardi Umberto , Bisi Giovanni , Vitolo Umberto 
Published: April 2020

Abstract
Introduction: The addition of antibody monoclonal anti CD20 Rituximab to CHOP chemotherapy resulted in improved CR, progression free survival and overall survival rates for patients with diffuse large B cell lymphoma (DLBCL). RIT with Zevalin, as single agent, has been shown to be effective in the treatment of relapsed refractory elderly DLBCL, namely in Rituximab naïve patients. However, in patients pretreated with Rituximab the reported response rate was lower. The aim of this study was to evaluate the efficacy and safety of Zevalin in a group of patients with relapsed or refractory aggressive lymphoma, all heavily pretreated with Rituximab containing regimens.
Patients and methods: Inclusion criteria were as follows: age over 18 yrs; relapsed or refractory CD20+ aggressive lymphoma (follicular grade IIIb, PML or DLBCL); WHO performance status of 0 to 2; stage II bulky, III or IV; bone marrow involvement &lt;25 %; written informed consent approved in accordance with institutional guidelines. All patients were previously treated with ≥ 2 lines of Rituximab containing regimens. Patients with pre-treatment platelet counts of &gt; 150 × 109/l received Zevalin at 0.4 mCi/kg whereas those with platelets &lt; 150 109/l received 0.3 mCi/kg.
Results: 24 patients were treated with RIT. Five patients had stage II, and 19 stage III/IV; bone marrow involvement was present in 11/24. Nine patients had grade IIIb follicular, 14 DLBCL and one mantle cell lymphoma. Eighteen patients received 0.4 mCi/kg and six patients 0.3 mCi/kg. Eleven patients were treated with RIT alone, six received RIT after standard salvage chemoimmunotherapy and seven were treated with RIT in combination with BEAM and subsequent autologous stem cell transplantation (ASCT). Status of disease before Zevalin treatment was: progressive disease (PD) in 14; complete response (CR) and partial response (PR) after salvage chemoimmunotherapy in 4 and 6 patients respectively. All patients in CR before RIT (4/24) maintained a continous CR after treatment. Overall response rate (ORR) after RIT for patients not in CR (20/24) was: 4 patients (20%) achieved a CR, 7 patients (35%) a PR and 9 patients experienced no response/progression (ORR 11/20 patients 55%). Six of seven patients treated with RIT + BEAM + ASCT achieved a response (CR 4 patients and PR 2 patients), one patient progressed immediately after the end of program. ORR in 11 patients treated with RIT alone and in six patients treated with chemotherapy + RIT were 46% and 50% respectively. With a median follow up of 32 months, OS and PFS rates were 67% and 52%. Eight patients died, all because of lymphoma. The most common grade 3–4 adverse events were neutropenia and thrombocytopenia.
Discussion: the results of this study suggest that RIT with 90Y-Ibritumomab Tiuxetan is a safe and effective treatment for patients with relapsed/refractory aggressive lymphoma even if they were pretreated with Rituximab containing chemotherapy.