Bruce D. Cheson, MD


February 01, 2013

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Hello. This is Bruce Cheson [from Lombardi Cancer Center, Georgetown University Hospital, in Washington, DC] for Medscape Hematology. I am here to update you on a few exciting results from the American Society of Hematology meetings held in Atlanta, Georgia, in December 2012. Several themes caught my attention. The first of these was the BRIGHT study.[1]

As you know, in 2009 the StiL Group from Germany presented results that were updated last year, but still unpublished, comparing R-CHOP (rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone) with R-bendamustine in previously untreated patients who had a variety of histologies of lymphomas, including follicular, marginal zone, lymphoplasmacytic, mantle cell, and so on.[2]

They showed that the overall response rates (> 90%) were comparable. The complete response rate was significantly higher with the bendamustine-containing regimen, and the progression-free survival was significantly longer [with R-bendamustine] -- a median of 69.5 vs 31 months with R-CHOP. It was twice as long. The toxicity was significantly better with the bendamustine-based therapy, particularly when it came to neutropenia, infections, neuropathy, and stomatitis. Worse, however, were the skin reactions one frequently sees with bendamustine.

This study has resulted in a major shift in practice. More and more patients are receiving R-bendamustine vs R-CHOP in the community and academic centers based on these results. Again, the results are not yet published.

Now, along comes the BRIGHT study, presented at the ASH meeting.[1] This was a collaborative study [from centers in] North America, Australia, and New Zealand that compared R-bendamustine with R-CHOP or R-CVP (cyclophosphamide/vincristine/prednisone) in patients with similar histologies who had not been treated previously. This was a noninferiority study. Complete response rates were similar: 31% with R-bendamustine and 25% with either R-CHOP or R-CVP. The overall response rate was 97% [with R-bendamustine] vs 91% [with R-CHOP or R-CVP], which met the noninferiority endpoint. This held true whether you compared R-bendamustine vs R-CHOP or R-bendamustine vs R-CVP. However, with very short follow-up, the progression-free survival curves were virtually superimposable, until the very end when they seemed to separate a little bit [but again, the follow-up was short] -- quite in contrast to the StiL study.

Of importance, the adverse-event profile was not quite as favorable for R-bendamustine as it had been in the German [StiL] trial. Patients in the R-bendamustine group reported more nausea and vomiting, fevers, chills, hypersensitivity, drug reactions, rash, pruritus, and more opportunistic infections. Patients receiving the other regimens reported more constipation, paresthesias, neuropathies, alopecia, and mucosal inflammation.

What do we do with these data? I am not sure, but it is critical that we see the final reports of both of these studies in some published form so that we can compare, contrast, and analyze.

In my own experience, I have found that patient response to R-CHOP and R-bendamustine is a mixed bag. Some [patients] say that one is easier than the other, but I have heard the contrary from other patients. Some pharmacogenomic issues must be involved. I do not know, but I came away from ASH with less certainty as to the relative roles of these 2 regimens. I think we have to define the various populations in which one might be better than another. Clearly, R-bendamustine is not inferior to R-CHOP, and it is a perfectly acceptable frontline therapy but we need longer follow-up and more data.

This is Bruce Cheson signing off for Medscape Hematology. Have a good day.