RIT with 90Y Ibritumomab Tiuxetan in Agressive Non-Hodgkin Lymphoma. Evaluation of Recent Outcomes in a Single Institution
Authors: Montes Anel , Andrade Ma , Murillo Ilda , Lopez-Gomez Luis , Baringo Teresa , Giraldo Pilar 
Published: October 2019

Abstract
Abstract 4883
Diffuse Large B Cell (DLBC) and Mantle Cell Lymphoma (MCL), are two subtypes of aggressive non-Hodgkin lymphoma (A-NHL),that frequently present as advanced systemic disease limiting the use of involved field radiation. They are also predominant in advanced age population non suitable for intensive therapy such as stem cell transplantation. Their aggressive systemic behavior, confer high rates of relapse and short overall survival. The development of radioimmunotherapy brings a new therapeutic approach for both types of A-NHL. We present the results derived from a single-institute use of 90Y-Ibritumomab Tiuxetan (90Y-IT) (Zevalin®) in DLBC and MCL, both as consolidation therapy in first complete response (C-1CR) after chemoimmunotherapy and as second line treatment in relapsed disease (RD).

Patients and Methods:
we included 19 patients with A-NHL, 10 MCL and 9 DLBCL, treated with 90Y-IT according to a multidisciplinary clinical protocol, between September 2005 and February 2012. Inclusion criteria were: histological confirmed CD20+ MCL or DLBCL, with absolute neutrophil count (ANC) ≥ 1.5 × 109/L, absolute platelet count (APC) ≥ 100 × 109/L, ≤ 25% bone marrow CD20+ lymphocytes, in Complete Remission (CR) after first line chemoimmunotherapy or with relapsed disease. All patients received two prior 250 mg/m2 Rituximab doses, followed by 0.4 mCi /kg IV 90Y-IT. Response was evaluated by PET/TC 12 weeks after treatment. Major endpoints were: objective response rate (ORR), overall survival (OS), progression free survival (PFS), and safety. Other clinical prognostic factors were taken into account upon their possible influence in treatment value.

Results:
18 of 19 patients treated with 90Y-IT completed follow-up and were taken into analysis, 10 MCL (52.6%) and 9 DLBCL (47.4%); M/F distribution 10/9 (73.6/26.4%); Overall ECOG 0–1 82.35%. Mean follow-up time: 46.8 months. 8 patients were treated as C-1CR, 4 MCL and 4 DLBCL. For MCL mean age was 66.9 (53–79) years. MIPI score distribution: 0–3 (70.0%), >3 (30.0%). Status before 90Y-IT was: C-1CR 3; relapsed in CR after chemotherapy 3; relapsed/refractory with active disease after chemotherapy (PR) 4. Previous chemotherapeutic schedules: ≤2 (50 %). Overall response (80.0%) 7 CR; 1 PR. Mean estimated OS since 90Y-IT: 57.0 months (52.4–61.6), median OS: 59 months (34.8–86.1) and mean PFS: 24.9 months (95% CI: 14.3–35.6); median PFS: 22 months (95% CI: 1.9–42.0). For DLBCL: mean age 53 (35–87) years. IPI-R score distribution: 0–2 (33.3%), >2 (66.7%). Status before 90Y-IT was: C-1CR 5; relapse/refractory with active disease after chemotherapy (PR) 4; Previous chemotherapeutic schedules ≤2 (77.8%). Overall responses (88.8%) 5 CR; 3 PR. Mean OS since 90Y-IT: 49.2 months (42.8–55.6); median OS: NR and mean PFS: 39 months (95% CI: 22.6–55.4). Until analysis 11 patients have relapsed (57.8%), 8 MCL (80%) and 3 DLBCL (37.5%). Four patients had died, 3 because of disease progression even after several chemotherapeutic treatments. In respect to safety: thrombocytopenia was the most frequent hematologic toxicity presented in 63.1%, grade 3–4 in 21%, with median time to presentation of 2.8 weeks and median time for recovery of 3 weeks. Neutropenia occurred in 52.6%, grade 3–4 in 21%, with median time for recovery of 2 weeks. 1 patient (5.2%) required red cell transfusion and 4 (21.5%) needed platelet transfusion. The most frequent non hematologic toxicity was asthenia. One MCL patient who relapsed 28 months and received 2 more chemotherapy schedules has been diagnosed, four years after 90Y-IT as lung carcinoma.

Conclusions:
90Y-IT is a safe and effective consolidation therapy in A-NHL, that allows sustained CR and extends PFS with a low toxicity profile. There are needed further studies to evaluate the impact of radioimmunotherapy in A-NHL.
This worh has bee partially sponsored by a grant from FEHHA

Disclosures:
No relevant conflicts of interest to declare.