Bruce D. Cheson, MD


December 02, 2011

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Good morning and welcome to Medscape Hematology. I am Bruce Cheson from Georgetown University Hospital, the Lombardi Comprehensive Cancer Center. It is 3 days before Thanksgiving. Do you know what that means? The American Society of Hematology (ASH) meetings are coming up. I just wanted to give you an idea of some of the things that I think will be interesting to see here. If you feel that you can't go to certain ones, because there are so many sessions that compete with one another, then here is a list of half a dozen that I am really going to try to attend.

Hodgkin lymphoma. There sure has been a lot about Hodgkin lymphoma, particularly with the approval of brentuximab vedotin, the SGN-35 antibody-drug conjugate. The controversy regarding the role of radiation therapy continues to exist. With regard to the ASH meetings, I am not going to give you any of the results because I'm not allowed to; you can look them up online. The study by Ralph Meyer and the National Cancer Institute of Canada Clinical Trials Group, which was published in 2005 in the Journal of Clinical Oncology,[1] randomized patients with early-stage disease to ABVD with or without subtotal nodal irradiation. There were some other nuances about risk factors, etc. At the time of initial publication, there was a slight benefit for the radiation group. I think it was 93% vs 87% progression-free survival and not much of any survival advantage. Now, after 11.3 years of follow-up, we will be looking for the consequences of the radiation. Will this study resolve the controversy about whether radiation should be included? Probably not, because it was subtotal nodal irradiation. Since that time, we moved to involve fields and node radiation. At least it will be interesting, important, and something else to continue to stoke the fire.

Chronic lymphocytic leukemia. There is a lot of interest in the role of new molecules, small molecules, and targeted therapies. How quickly can we move them up front? An interesting paper will be presented that combines rituximab and lenalidomide -- a so-called R-squared regimen -- as the initial therapy for chronic lymphocytic leukemia. It would be nice to get away from chemotherapy for certain subpopulations of patients.

T-cell lymphoma. For a long time we didn't care much about T-cell lymphoma sessions because there wasn't much to talk about. Now we have a bunch of new drugs. Again, brentuximab for the anaplastic large cell and, I predict, for some other histologies in the future. Jonathan Friedberg will be presenting data on an Aurora A kinase inhibitor in aggressive B-cell and T-cell lymphoma. Rumor is that, particularly for T-cell lymphoma, the results may be of interest. In fact, there is an intergroup study, with SWOG and Cancer and Leukemia Group B (CALGB), which is a phase 2 trial of this inhibitor in patients with relapsed and refractory peripheral T-cell lymphoma. We really need to get away from CHOP chemotherapy. The only way we are going to do this is to have some exciting drugs in the relapse setting, combine them, and move them up front. That is where things are headed. There are also some antibodies out there. There will be some data presented on those at the ASH meetings.

Radioimmunotherapy. What really surprised me is how many abstracts are on the oral session for radioimmunotherapy in lymphoma. Radioimmunotherapy is probably the most effective, least used treatment for lymphoma. It has been out there for years, and yet very few patients receive it for a whole variety of reasons. There is a session that is almost completely devoted to radioimmunotherapy. What I fancy is an important trial, being a coauthor, is Oliver Press' SWOG-led intergroup study, which was R-CHOP vs CHOP followed by I-131 tositumomab. This was initially a 3-arm study with CHOP, but they couldn't accrue it. No one wanted to put patients on CHOP alone, so these were the 2 arms. If one arm is clearly superior, that's easy, but what if they are similar? Which one would be the preferable regimen, R-CHOP x 6 with no maintenance or CHOP x 6 with radioimmunotherapy following it for about 7 days? It will engender interesting discussions and raise controversy. We probably would have been better off with R-CHOP vs R-CHOP followed by radioimmunotherapy, but we don't have that. I am interested to see how the data will be spun.

There will be some additional data with Y-90 ibritumomab tiuxetan as front-line therapy. There will be some more data presented on consolidating initial therapy with radioimmunotherapy, such as the previously published and updated First-Line Indolent Trial (FIT). Whether these data will stimulate more physicians to use radioimmunotherapy in the treatment of lymphoma remains to be seen, but it sure is not used very much.

I think it was the American Society of Clinical Oncology (ASCO®) meeting where there was a presentation on relapsed refractory follicular rituximab with or without bortezomib, which showed a slight advantage to adding bortezomib in activity or efficacy, but certainly not with regard to adverse events. The study did not meet its primary endpoints. The company, as a result, realized that it was indeed a negative study and decided not to pursue that indication, but at this meeting they are going to try to identify certain subsets of patients who might benefit from the combination of the 2 drugs. I think it is better to move on, but there will be considerable discussion of a new anti-CD20 monoclonal antibody (GA101), obinutuzumab. GA101, a glycosylated anti-CD20, has been shown to be active and well tolerated. There are several abstracts at the ASH meeting. There will be an update of the single-agent data. There will be some data on combining the antibody with FC or with CHOP, but I think most interesting will be the third abstract, because I have always said that there are only 2 real ways a new anti-CD20 will supplant rituximab: (1) It has to be active when rituximab is not, or (2) It has to be more active than rituximab in a head-to-head comparison. Randomized phase 2 data from such a comparison are going to be presented, GA101 vs rituximab.

I think those are some of the more interesting abstracts that I plan on seeing. There are many more on myeloma, acute leukemias, chronic myelogenous leukemia, etc. These are the ones that I am going to try to see. I hope to see you at ASH because I think it is going to be an important meeting, and we can have some further discussions about what we did see once we get back from San Diego. This is Bruce Cheson signing off for Medscape Hematology. For those of you who are going to ASH, have a good trip. If you are not, we will let you know what we saw. Thank you.