Select Excerpts from the Interview*

CD 1, Track 8

DR LOVE: I’m curious about your thoughts on the RESORT trial comparing R followed by R maintenance versus R alone and R re-treatment on progression. I find it interesting that maintenance therapy is given indefinitely, as opposed to being given for two years.

DR HAGEMEISTER: I love the maintenance program in this study — it’s based on real data from the Gordon trial. I like the idea, ultimately, of giving the rituximab as maintenance, until the patient develops disease progression.

This is a very interesting study (1.1); however, I would love to see an additional question addressed, and that is, Will patients who subsequently are treated with chemotherapy — or whatever additional therapy they receive when they develop progressive disease — will patients on both arms have the same responsiveness to chemotherapy? There is a suggestion that patients who are “refractory” to rituximab tend to be resistant to chemotherapy agents.

However, there are no clinical data to support that. In fact, patients seem to have more favorable disease at the time of recurrence and survive for longer periods of time, it appears, when they receive rituximab as therapy. Although there’s no real hard, strong data right now in a randomized study to demonstrate that, there is a strong suggestion that patients are living longer because they receive rituximab.

The Hainsworth study of R maintenance is in patients with relapsed lymphomas, not front-line therapy. With these patients, time to treatment failure is better when you give maintenance rituximab, but time to receiving other drugs or a new treatment is no different whether you adopt a maintenance therapy or a re-treatment therapy.

What will ultimately answer this question is the PRIMA study, which evaluates R-chemotherapy followed by rituximab maintenance every three months for two years versus none (1.2). In that trial, it may be that rituximab maintenance actually ends up prolonging the patient’s time to treatment failure — but maybe not survival.

CD 1, Track 12

DR LOVE: Would you provide an update of your study of rituximab plus GM-CSF?

DR HAGEMEISTER: We’ve been conducting a study that shows that administering GM-CSF along with rituximab leads to much higher complete response rates than we see with single-agent rituximab. It was not a randomized study, and it wasn’t in patients who were rituximab resistant. In fact, patients had to have sensitive disease. They had to have a response to their last rituximab treatment that lasted at least six months in order to be entered on the study.

Recently, Peter McLaughlin presented our data at the lymphoma meeting in Lugano, Switzerland. The complete response rates are in the range of 40 percent. They’re very dramatic. We’ve treated approximately 75 patients, and the side effects have not been any more than what you would expect with rituximab as a single agent.

Patients didn’t receive maintenance therapy on the trial. The most interesting aspect of that whole study is that we actually demonstrated that ADCC (antibody-dependent cellular cytotoxicity) is upregulated by the administration of GM-CSF.

We’re currently considering this as a new study — a Phase II/III study with rituximab/GM-CSF in patients with indolent follicular lymphoma who have zero to one adverse feature in the Follicular Lymphoma International Prognostic Index (FLIPI) score.

CD 1, Track 14

DR LOVE: Fernando Cabanillas has discussed the concept of cure, or extended survival, in patients treated for indolent lymphoma, and the series of trials that have been done at MD Anderson (1.3). What are your thoughts on that?

DR HAGEMEISTER: We’ve demonstrated in sequential trials that survival appears to have improved continuously over the last 30 years, first with CHOP alone or CHOP-Bleo initially, then with CHOP/interferon and, ultimately, with alternating triple therapy plus interferon. Then, when we introduced FND, things also significantly improved, and finally, with the addition of rituximab in the last five years — more than 90 percent of those patients are still alive at five years with R-FND-type therapies (Liu 2003).

DR LOVE: Fernando talked about a plateau in the curves at eight years. What are your thoughts on that?

DR HAGEMEISTER: We’ve evaluated patients who have Stage IV follicular lymphoma who were all submitted for the FLIPI analysis. Every patient had Stage IV disease and had been treated on a trial.

We looked at time to progression and after about nine or 10 years, approximately 40 percent of the patients who have a low beta globulin serum tumor marker have not developed progressive disease, and there is very definitely a plateau out to 15 years.

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* Conducted on August 10, 2005