ASH Conference: Radioimmunotherapy as Part of First Line Therapy for Low Grade Lymphoma

By Rebecca Elstrom, MD

Update: this study is closed to enrollment. 

Radioimmunotherapy (RIT), or radiation targeted to lymphoma cells through conjugation to a monoclonal antibody, has long been known to be effective therapy in patients with relapsed indolent non-Hodgkin’s lymphomas.  Its use as first line therapy has been limited, however. This weekend at the American Society of Hematology (ASH) meeting, several studies exploring the use of RIT in initial therapy of low grade lymphomas, either alone or following chemotherapy, were reported.

Two studies explored the use of 90Y-ibritumomab tiuxetan (Zevalin) alone;  one presented by Dr. Pica of Genova on behalf of an Italian cooperative group exploring a single dose, and one presented by Dr. Illidge from the University of Manchester with fractionated dosing (multiple doses of the RIT, in this case 2). Both studies showed high response rates with this brief and simple strategy, and durations of remission comparable to front line chemotherapy with no excessive toxicity.

Two other studies explored the use of RIT as consolidation following initial chemotherapy. The first, presented by Dr. Press of the University of Washington, was a large multicenter study comparing Rituximab plus CHOP chemotherapy (R-CHOP) to CHOP followed by 131I-tositumomab (Bexxar). There was no difference between the two groups in response rate or duration of response. A caveat to this study is the fact that, at the time it was designed, there was concern that giving the anti-CD20 antibody rituximab prior to RIT would inhibit radiation dose delivery, as 131I-tositumomab also requires binding to CD20 in order to deliver the radiation dose to lymphoma cells. This concern does have support in laboratory studies, but it has become clear in the years since this study was designed that anti-CD20 antibody therapy with rituximab is a critical contributor to response and survival in follicular lymphoma. The second study of chemotherapy followed by RIT was presented by Dr. Fowler of MD Anderson Cancer Center. This group evaluated an induction chemotherapy regimen containing rituximab, fludarabine, mitoxantrone and dexamethasone (R-FND) followed by 90Y-ibritumomab tiuxetan. This study showed high response rates and long time to progression, but toxicity of the regimen was of some concern, possibly due to the fact that fludarabine has significant bone marrow suppressive effects, which is also the main side effect of RIT.

Overall, these presentations confirmed the impressive activity of RIT in low grade lymphoma, and extended the experience using RIT as part of first line therapy, demonstrating feasibility, safety and efficacy of this simple and very well tolerated therapeutic approach.

At Weill Cornell Medical College we are exploring radioimmunotherapy as first treatment of follicular lymphoma using a combined strategy of non-radiation tagged antibody to CD20 in combination with radio-labeled antibody against an alternative protein, CD22. This study is designed to maximize the benefit of anti-CD20 directed therapy in addition to radiation dose delivery by targeting the radio-labeled antibody to an alternative target. Click here to read more about this study.

Follicular Lymphoma Clinical Trial

Combination Veltuzumab (Anti-CD20) and Fractionated 90Y- Epratuzumab (Anti-CD22) Radioimmunotherapy in Patients with Follicular Lymphoma

Update: this study is closed to enrollment. 

Monoclonal antibodies can fight lymphoma by binding to proteins expressed on lymphoma cells and either directly killing or inducing the immune system to kill the tumor cells.

With radioimmunotherapy, the antibody is labeled with a radioactive molecule, allowing directed delivery of radiation to the lymphoma.  Radioimmunotherapy is effective in follicular lymphoma, but immune reactions against the radiolabeled antibody have limited the utility of this approach.

In this study, we are evaluating the combination of an unlabeled antibody to one lymphoma-associated protein (CD20) with a radio-labeled antibody to a different lymphoma-associated protein (CD22), in hopes of improving responses. The antibodies are modified to minimize immune responses, and both antibodies will be given in repeated doses in order to increase the total amount of drug administered while limiting side effects.

Eligibility:

  • Follicular lymphoma
  • No more than 2 prior systemic treatments for non-Hodgkin’s lymphoma
  • Detailed eligibility discussed when you contact the study team

For more information, contact June Greenberg, RN at (212) 746-2651 or jdg2002@med.cornell.edu.

Click here to view all lymphoma clinical trials at Weill Cornell Medical Center.