Select Excerpts from the Interview

CD 1, Track 24

DR LOVE: What are the reasonable options for initial therapy for patients with diffuse large B-cell lymphoma with adverse prognostic features?

DR WILSON: I think it’s clear that R-CHOP is the standard. But even with R-CHOP, we know from the GELA study (Feugier 2005; Coiffier 2003) that patients who are over the age of 60 with a poor prognosis do relatively poorly. We don’t know about people under 60 with poor prognosis, because MInT (Pfreundschuh 2004a; [3.1, page 15]) involved people who had a favorable prognosis.

We’ve been very interested in the development of better therapies. That’s why we developed dose-adjusted EPOCH-R. With this regimen, the poorprognosis groups have event-free survivals over 50 percent. Therefore, I would say that a regimen like EPOCH-R probably should be considered.

Patients who have a good prognosis will also benefit from this regimen. According to the results from our trial at the NCI, in which we have around 70 patients (Wilson 2004), and the CALGB study (Wilson 2005), neither of which involves radiation, event-free survival is 94 percent in patients over 60. In our study, we’ve never seen a single failure beyond 17 months.

CD 2, Track 1

DR LOVE: What are your thoughts about the dose-dense approach in terms of both the clinical data and the theoretical considerations?

DR WILSON: Dr Pfreundschuh conducted a four-arm study that compared CHOEP and CHOP administered either every 14 or every 21 days. The patients were divided into one study for those over 60 years of age and one study for those 60 years of age and under. What was a little bit unclear was that in the patients over 60, CHOP-14 worked (Pfreundschuh 2004b; [3.2, page 16]), but in the patients under 60 years of age, dose density didn’t have an impact, but receiving etoposide improved event-free survival (Pfreundschuh 2004c; [2.1]).

The biology of the tumors is not radically different between people over and under 60 years of age. So it was not clear why dose density was not effective in people 60 years and younger and did work in people older than 60. Furthermore, a Japanese study of dose density didn’t show a benefit. In fact, they stopped the study (Hotta 2003). Then Dr Pfreundschuh looked at R-CHOEP versus R-CHOP and noted that rituximab was the “great equalizer” (Pfreundschuh 2005; [2.2]).

CD 2, Track 8

DR LOVE: What do you think are reasonable options in the clinical setting for first-line treatment of patients with mantle-cell lymphoma?

DR WILSON: One of the things people don’t realize is that mantle-cell disease is a disease you can sometimes watch. It’s also a disease with a median age of approximately 60 years, and it can be indolent in a fair number of patients. So, depending upon the patient’s age and the tempo of the disease, it’s certainly reasonable to consider “watch and wait” for some folks. When it comes to treating patients, this is going to depend also on the doctor’s goals. For younger patients, emerging evidence suggests that allogeneic transplant may be able to provide some benefit.

As far as choice of therapy, I think it’s dealer’s choice. I’m quite excited by the results that have been reported with bortezomib (O’Connor 2005; Goy 2005). In fact, we have just begun a new study using that drug up front. I believe we will begin to see bortezomib/rituximab combinations. We also have the report from the Austrian group of rituximab and thalidomide (Kaufmann 2004). And, of course, there’s the old standby, R-CHOP. While R-CHOP has a median event-free survival of about 18 months (Lenz 2005), if a patient has bulky disease, you may want to use bigger guns.

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