A Phase 2 Study of 90Y-Ibritumomab Tiuxetan (90Y-Zevalin®) in Relapsed/Refractory Non-Hodgkin’s Lymphoma: Preliminary Report of the Argentinean Cooperative Group.
Authors: Cacchione Roberto E. , Milone Jorge , Bordone Javier , Dupont Juan , Milone Gustavo , Riveros Dardo , Negri Pedro , Ardaiz María , Riera Leandro , Foncuberta Maria Cecilia , Bezares Fernando 
Published: April 2020

Abstract
Background. In our experience, in Argentina, the use of rituximab + chemotherapy in relapsed/refractory CD20+ follicular (FL) non-Hodgkin’s lymphoma results in &lt;1 year progression-free survival. 90Y-Zevalin® (90Y-ibritumomab tiuxetan), a radiolabeled antibody to CD20, has shown promising activity in this patient population. We present the initial outcome of a phase 2 trial conducted by the Argentinean Cooperative Group, using 90Y-Zevalin for relapsed refractory FL and transformed lymphomas.
Methods. Between September 2005 and November 2005, we recruited 10 patients (pts; 6 male/4 female; median age = 56 yr [range: 45–71 yr]) with platelets &gt;100,000/mm3 and bone marrow involvement &lt;25% for this trial. Nine pts had FL and 1 pt had mantle cell lymphoma. Four pts had bulky disease (largest diameter &gt;5 cm). Three pts were Ann Arbor stage I or II and 7 pts were stage IV. Three pts had received 1–2 cycles of rituximab + chemotherapy and 7 pts had received 3–5 previous cycles. Three pts had undergone autologous transplant. Pts received rituximab 250 mg/m2 IV on days 0 and 7. After the second dose of rituximab, pts received 11 MBq (0.3 mCi) 90Y-Zevalin per kg or 15 MBq (0.4 mCi) 90Y-Zevalin per kg based on platelet counts, with a maximum dose of 32 mCi. Blood counts were monitored weekly until week 10 post-treatment and monthly thereafter. Patient tumor response was reevaluated 3 and 6 months after treatment according to standard criteria.
Results. Five pts received a complete dose of 0.4 mCi 90Y-Zevalin per kg and 5 received a reduced dose of 0.3 mCi 90Y-Zevalin per kg. The overall response rate was 60% (CR = 5, PR = 1). Table 1 summarizes the responses. The 5 pts with a CR remained disease-free 8 months later. The pt with a PR progressed with adenopathies and visceromegaly 7 months after treatment. Seven of 10 pts experienced hematologic toxicity: 5 of these 7 pts required G-CSF because of grade 3/4 neutropenia and 3 of these pts developed neutropenic fever. Four of the 7 pts required platelet transfusions and 2 of them required red blood cell transfusions. All 3 pts with previous autologous transplant were in the group with hematologic toxicity. All of these pts required G-CSF and transfusion support, and 2 of these 3 pts were admitted to the clinic for this treatment; hematologic recovery occurred by week 9 post-treatment.
Conclusion. The use of 90Y-Zevalin in the relapsed/refractory NHL setting resulted in better response rates and longer disease-free survival than with standard chemoimmunotherapy. Our finding with 50% CR in a heavily pretreated cohort, including 42.8% CR in stage IV pts and 33% CR after autologous transplantation, is encouraging. We are continuing to follow these patients.
Table CR PR NR/PD Previous transplant (n=3) 1 1 1 Mantle cell (n=1) 0 0 1 Follicular (n=9) 5 1 3 Tumor volume &gt; 5cm (n=4) 1 0 3 Tumor volume &lt;5 cm (n=6) 4 1 1 Stage I or II (n=3) 2 0 1 Stage IV (n=7) 3 1 3