Select Excerpts from the Interview*

CD 1, Track 17

DR LOVE: One of the most discussed publications in lymphoma this year was your paper in The New England Journal of Medicine evaluating radioimmunotherapy as first-line treatment for follicular lymphoma (Kaminski 2005). Can you comment on the background to that trial?

DR KAMINSKI: We performed a lot of the developmental work on radioimmunotherapy with CD20 radio-labeled antibodies. We had shown how to administer it, what its toxicities were and where its greatest value appeared to be, which was in the follicular lymphomas. We had also done a lot of work in patients with refractory disease, and it was working in them.

The natural idea here is that if it works in the back-line setting, it should work even better in the front-line setting, where there’s less potential resistance — the patients are more immunocompetent. So especially in an incurable disease such as follicular lymphoma, it made all the sense in the world to use something that appeared in some of our trials to be superior to chemotherapy as front-line therapy.

The trial evaluated Bexxar in patients with Stage III and IV follicular lymphoma — advanced-stage disease — with no prior treatment. Our first patient was accrued in June of 1996, so we have quite a long follow-up on these patients. The first-patient phenomenon worked in this trial: That patient is still in complete remission.

DR LOVE: Can you summarize the data that you recently reported in The New England Journal of Medicine?

DR KAMINSKI: We showed in 76 patients that we could achieve a 95 percent response rate with only one course of treatment, which only takes a week to give, and a 75 percent complete remission rate (2.1). We now have long-term follow-up — the median follow-up is over five years — and the progression-free survival at five years is 60 percent for all the patients entered on the trial.

Of those who had a complete response, more than 70 percent — 75 percent — were still in remission at five years. At this point, an abundant number of patients are beyond five years. We only had four relapses, and of those four, three relapsed only in a solitary site, and we treated that with conventional radiation therapy and put them back into remission. That’s one aspect.

The other aspect of this trial was that we were interested to see if we could induce a molecular remission. If the treatment had any chance of being a potential cure, to be molecularly negative would certainly be going a long way in that direction, so we actually measured the Bcl-2 translocation using PCR techniques, serially, in the bone marrow of these patients. We found that of the patients who had the Bcl-2 translocation, more than 90 percent showed molecularly negative results at some point in the follow-up.

CD 1, Track 20

DR LOVE: What did you see in terms of short- and long-term toxicities?

DR KAMINSKI: Myelodysplastic syndrome and acute myelogenous leukemia are the long-term toxicities we’re most concerned about, and we didn’t see any — zero — with a median follow-up of five years.

As for the short term, the major toxicity is hematological (2.2). It occurs at about six to seven weeks in terms of the nadir of blood counts, but none of these patients had to have any transfusions. No one had febrile neutropenia requiring hospitalization or antibiotics, and none of them received growth factors; it was very well tolerated.

CD 2, Track 3

DR LOVE: In the clinical management of indolent lymphomas, where does radioimmunotherapy generally fit into your algorithm?

DR KAMINSKI: I try to utilize it as early as possible in the course of the disease. If a patient has had a long remission with chemotherapy and then they require more therapy, we have the options to give just rituximab or go on to give additional chemotherapy or to give radioimmunotherapy. I would clearly use radioimmunotherapy in patients who have short responses to chemotherapy and who have relatively poor responses to rituximab.

In general, because of the simplicity of the treatment and the brevity of it, I really have a hard time not thinking of radioimmunotherapy for a patient who has relapsed with a follicular lymphoma if the disease is progressing and is potentially beginning to become or is symptomatic. That’s where the highest complete response rates are, and that’s where the duration of response is greatest. If you obtain a complete response, you have an excellent chance of remaining that way for five years, and very few chemotherapeutic approaches out there demonstrate that.

Select publications

* Conducted on April 8, 2005