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.