Radioimmunotherapy: How Strong an Option Is It?

Bruce D. Cheson, MD


January 20, 2012

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Hello and happy New Year. This is Bruce Cheson from Georgetown University Hospital, the Lombardi Comprehensive Cancer Center. This is Medscape Hematology.

Within the last couple of weeks, I have written 2 prescriptions for radioimmunotherapy for patients with refractory and relapsed follicular lymphoma. I can't remember the last time I prescribed this form of treatment. It is a very effective therapy. In fact, it is probably the most effective yet least used treatment for follicular lymphoma.

For patients with relapsed and refractory disease, the published response rates have ranged from 60% to 80%. There are 2 drugs on the market and their activity is similar. One is I-131 tositumomab (Bexxar®) and the other is Y-90 ibritumomab tiuxetan (Zevalin®).

At the American Society of Hematology (ASH) meetings, there were a number of abstracts presented.[1,2,3,4,5] In fact, almost a whole session was on radioimmunotherapy, which surprised me because it doesn't seem to be used very often. In 2005, there was a paper in the New England Journal of Medicine suggesting that the I-131 compound, when used as initial treatment for follicular lymphoma, had about a 95% response rate and that a lot of these responses lasted for years.[6]

At the ASH meetings, there was a presentation on fractionated administration of the Y-90 compound in a relatively small series.[1] Almost every patient responded. There were some relapses with relatively short follow-up. There were some other papers that also suggested that the drug was potentially useful.

A number of years ago, the First-Line Indolent Trial (FIT) was published.[7] In this study, patients with follicular lymphoma received induction chemotherapy, occasionally rituximab-based therapy. If they did not progress, they were randomly assigned to receive Y-90 ibritumomab tiuxetan or observation. There was a significantly longer progression-free survival with radioimmunotherapy consolidation. This led to approval of this strategy for follicular lymphoma. Nevertheless, I have not seen it used in the several years since publication of this study.

Adding a little more to this controversy is an important abstract that was presented by Oliver Press.[2] The study was a North American intergroup trial with SWOG [formerly the Southwest Oncology Group], Cancer and Leukemia Group B (CALGB), and the Eastern Cooperative Oncology Group (ECOG). Patients were randomly assigned to initial therapy with CHOP, CHOP-R [rituximab], or CHOP followed by I-131 tositumomab. The arm with CHOP alone had to be dropped because the study wasn't going anywhere and no one wanted to recruit to a CHOP-only trial. These were the first results of the study. The primary endpoint was not met. In fact, the time to treatment failure and progression-free survival were the same in both arms. Whether there would have been a difference if it had been CHOP-R followed by radioimmunotherapy compared with CHOP-R, we don't know and we will probably never know, because who knows what is going to happen with radioimmunotherapy?

There are a number of problems that lead to the lack of use of this compound. It is very expensive and there were problems with reimbursement by the Centers for Medicare & Medicaid Services in the past. Additionally, it is not always available. Most of the time, the physician has to refer the patient to another institution or facility where there are radiotherapy or nuclear medicine capabilities to administer radioimmunotherapy.

There are concerns about secondary malignancies that I think are real. Although, up front, there has been no secondary acute myeloid leukemia or myelodysplastic syndrome, they have been seen in the relapsed setting and when radioimmunotherapy has been used to consolidate a chemotherapy program, so there is a concern. There are concerns about whether you can successfully and safely re-treat patients down the line. There are strict exclusion criteria based on the amount of bone marrow involvement by lymphoma and peripheral blood counts. It's not easy; you need to really coordinate among the people who are providing the therapy. The therapy itself is very easy; it's only 8 days -- day 1[premedication and rituximab], day 8 [premedication, rituximab, and 90-Y ibritumomab tiuxetan], and you're done. You monitor counts weekly for a while.

This is a good therapy in the appropriate situation. I think another issue is that we have so many other exciting new approaches for follicular lymphoma, with the kinase inhibitors, other monoclonal antibodies, and the drug antibody conjugates, that radioimmunotherapy is sort of forgotten in the process.

Where is radioimmunotherapy going and where will it be in 5 years? I can't say. All I can say is that, based on what we have seen, it is useful in appropriate patients. However, I don't expect its use to increase very much, if at all, after the SWOG presentation.

This is Bruce Cheson signing off for Medscape Hematology, and I will be speaking with you again in the near future. Thank you.


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