A Phase 2 Study of 90Y-Zevammab in Relapsed Refractory Non-Hodgkin's Lymphoma: Preliminary Report of the Argentinean Cooperative Group

Reviewer: Eric Shinohara MD, MSCI
Abramson Cancer Center of the University of Pennsylvania
Last Modified: March 22, 2007

Presenter: Cacchione, R
Presenter's Affiliation: CEMIC Argentina
Type of Session: Scientific


  • Non-Hodgkin’s Lymphoma (NHL) represents a diverse group of malignancies and has a variable presentation, ranging from indolent to aggressive. 
  • Diffuse large B-cell lymphoma (DLBCL) is the most common histological subtype. 
    • Though usually aggressive it can be treated definitively with standard immuno-chemotherapy.
  • Other subtypes, such as follicular lymphoma have a more indolent course and can have long periods of remission but generally relapse.
  • Rituximab is a chimeric antibody which targets CD20 on the surface of B-cells.  It has been shown to be effective in treating NHL, however, patients still tend to relapse.
  • Hence, new treatments with efficacy in patients who have relapsed or have refractory disease are needed. 
  • Radioimmunoconjugates are monoclonal antibodies bound to radioisotopes and have been shown to have efficacy in lymphoma.  The antibody is specific for surface antigens expressed on malignant cells allowing targeted delivery of radiation.
  • Yttrium (90Y) ibritumomab tiuxetan has been shown to have efficacy in relapsed and refractory low-grade, follicular or transformed lymphoma.  It is comprised of the antibody, ibritumomab which is a CD20 specific murine monoclonal antibody which is covalently bonded to the pure beta emitter, 90Y.  
  • Previous studies have shown that Yttrium (90Y) ibritumomab tiuxetan had superior response rates compared with rituximab in patients with relapsed or refractory low grade lymphoma.  However, no improvement in time to progression (TTP) or response duration was found.
  • The purpose of this prospective study was to address Yttrium (90Y) ibritumomab tiuxetan efficacy in patients with relapsed or refractory lymphomas who had already failed rituximab using the end point of complete response (CR).

Materials and Methods

  • 27 patients with refractory/relapsed lymphoma who had failed on rituximab were enrolled between September 2005 and February 2007.
  • All patients received rituximab 250 mg/m2 intravenously (IV) on days 0 and 7.  After the second dose patients received either 11 MBq (0.3 mCi) or 15 MBq (0.4mCi) per kilogram of Yttrium (90Y) ibritumomab tiuxetan based on platelet counts.  Maximum dose was 32 mCi. 


  • Median age was 58 years old (range 45-76) with fourteen women and thirteen men.  Twenty two patients had follicular lymphoma and five had mantle cell.  Sixteen patients had stage II-IV disease, ten had bulky disease and five had bone marrow involvement.  
  • Time from diagnosis was 0-3 years in five patients, 3-6 years in eight patients, and greater than 6 years in thirteen patients.  Eight patients had 1-2 previous courses of treatment, eighteen had 3-5 and five had previous bone marrow transplant.  
  • Tumor response was evaluated at 3 and 6 months after treatment.
    • Fifteen patients responded to treatment with eleven having a complete response (CR) and four having a partial (PR) response.  Ten of eleven patients remained in remission for between 3 to 15 months. 
    • Eleven patients required filgrastrim for neutropenia.  Eight required platelet transfusion.  Four required red blood cell transfusion.  Six had neutropenia with fever and five had to be admitted for pancytopenia.  One patient died 40 days after treatment from hypoplastic bone marrow and septicemia.  All five patients with previous bone marrow transplant required filgrastrim and transfusions.

Author's Conclusions

  • There was a 41% CR rate after treatment with Yttrium (90Y) ibritumomab tiuxetan who had previously failed Rituximab. 
  • Yttrium (90Y) ibritumomab tiuxetan appeared to be tolerated by patients with previous bone marrow transplant. 

Clinical/Scientific Implications

  • This study suggests that Yttrium (90Y) ibritumonab tiuxetan may be a safe treatment for patients with refractory/relapsed disease, even after several different treatments, including bone marrow transplant.  However, there was one death which appeared to be related to treatment.
  • To determine if the complete response rate in response to Yttrium (90Y) ibritumonab tiuxetan leads to differences in prognosis, larger studies with endpoints such as progression free survival and overall survival need to be performed.
  • Further studies of the maximum tolerated dose would be of interest, as the dose tolerated by patients without previous bone marrow transplant may be higher and be of therapeutic value.
  • It appears that Yttrium (90Y) ibritumonab tiuxetan has potential to be used as a salvage treatment in patients with relapsed/refractory disease though further studies to look at definitive endpoints or quality of life are needed.

See the patient-oriented summary of this study