Tracks 1-9

Track 1 New agents being evaluated in the treatment of lymphomas Track 2 DENSE-R-CHOP-14 trial: Dose-dense rituximab in elderly patients with diffuse large B-cell lymphoma Track 3 Clinical use of R-CHOP-14 Track 4 Tolerability of R-CHOP-14 in older patients Track 5 DENSE-R-CHOP-14 trial: Study design and results Track 6 Impact of rituximab serum levels on disease progression Track 7 Bendamustine versus chlorambucil for treatment-naïve patients with B-cell CLL: Pivotal trial results Track 8 Bendamustine-R versus CHOP-R in the first-line treatment of indolent and mantle cell lymphomas Track 9 Integration of bortezomib into treatment regimens for lymphomas

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Tracks 2, 5

DR LOVE: Can you discuss the trial of dose-dense rituximab with CHOP-14 in elderly patients with diffuse large B-cell lymphoma presented at ASCO 2008?

DR HAGEMEISTER: That trial demonstrated that if you administer rituximab more frequently — two times a week — then higher rituximab levels are sustained over a much longer period. Dose-dense rituximab also somehow imparts a better response rate and disease-free survival rate among patients with large-cell lymphoma (Pfreundschuh 2008a; [4.1]). The study was conducted with patients older than age 60, which is the population in which we’ve been using R-CHOP-14 clinically.

The caveat with this regimen is that you have to use trimethoprim/sulfamethoxazole and acyclovir as prophylaxis (Pfreundschuh 2008a), which we have not normally used with R-CHOP-21 but has been described by Memorial Sloan-Kettering with the use of standard R-CHOP-14. I’ve changed my practice — I use prophylactic trimethoprim/sulfamethoxazole and acyclovir for patients who receive standard R-CHOP-14.

DR LOVE: Would you discuss the study design and results?

DR HAGEMEISTER: It was a Phase II trial for which they selected patients with high-risk disease (Pfreundschuh 2008a). They compared these Phase II results to the results from their previous study (RICOVER-60) of R-CHOP-14 versus CHOP-14 (Pfreundschuh 2008b). The patients in the new study who received dose-dense rituximab and had worse risk features, such as more advanced disease, fared better. It was approximately a 10 percent improvement in progression-free survival after a short follow-up (Pfreundschuh 2008a; [4.1]).

I don’t know whether they’ll fall off eventually or how the data will ultimately appear. However, at an early point, it seems that using rituximab more frequently and obtaining higher rituximab levels in patients with large-cell lymphoma improve disease-free survival, time to relapse and other parameters (Pfreundschuh 2008a). Whether it will improve overall survival, I don’t know.

Tracks 7-8

DR LOVE: Can you review what we know about bendamustine in follicular lymphoma?

DR HAGEMEISTER: The German data comparing bendamustine with rituximab to R-CHOP that were presented at ASH 2007 were interesting. They demonstrated that bendamustine/rituximab was as efficacious as R-CHOP in patients with a variety of different indolent lymphomas. The data indicated a complete response rate of around 50 percent in patients with indolent or mantle-cell lymphoma (Rummel 2007; [4.2]). They suggest a role for bendamustine, particularly in combination with rituximab.

Track 9

DR LOVE: Where are we with bortezomib in lymphoma?

DR HAGEMEISTER: Evidence suggests that when you expose rituximab-resistant cell lines to bortezomib, you can make those cell lines rituximab sensitive. Evidence in cell lines also suggests that bortezomib is either additive or synergistic in combination with chemotherapy and other drugs. Ongoing studies are using rituximab with cyclophosphamide, bortezomib and prednisone (R-CBorP) for indolent lymphomas, substituting bortezomib for vincristine (Gerecitano 2008). Other trials are considering the addition of bortezomib in the treatment of mantle-cell lymphoma, indolent lymphoma and large-cell lymphoma.

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Neil Love, MD

INTERVIEWS

Steven D Gore, MD
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Michael J Keating, MB, BS
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William I Bensinger, MD
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Fredrick B Hagemeister, MD
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