DR FREIDBERG: In CLL, I think lenalidomide is an underutilized option by practitioners. I can think of probably at least 10 patients over the last year to year and a half where a standard therapeutic option would have been lenalidomide. And I don’t know that the practicing oncologist had considered that.
Lenalidomide is active in CLL, and although we’re a bit spoiled because of all these new agents, as far as an available agent it probably has one of the higher response rates in some of the poor-risk groups like deletion of chromosome 17. I use it as either a single agent or in combination with rituximab. And I think the key messages are, you have to worry about this tumor flare reaction where lymph nodes can sometimes swell, get very hot and uncomfortable for patients, as well as tumor lysis. And even 10 mg may be too high for certain patients to tolerate, particularly heavily pretreated patients. And I’ve often gone down to 5 mg a day or 5 mg even every other day for those patients.
And for the patients who respond, they often can stay on the drug for quite a long period of time. And I have not really had significant issues with tolerability over duration of time, with the exception of sometimes evolution of cytopenias that require dose adjustments.
DR LOVE: Chris?
DR FLOWERS: Jonathan brings up good points about the dosing of lenalidomide in CLL. I think this is an agent that looks to be active both as a single agent and in combination with rituximab. But you have to be somewhat careful about the dosing, depending on how late in therapy these patients are receiving lenalidomide, because of the cytopenias. I think another thing to be cautious of is how this agent is used in combination. So it looks to be active in combination with rituximab, but we had a small pilot trial looking at it in combination with rituximab and oral cyclophosphamide, where we were using the cyclophosphamide to try and avoid this tumor flare syndrome. And we saw little or no activity of that combination in the first 6 patients. And I think that’s in part due to the mechanism of action that is abundant there between the lenalidomide and rituximab, and probably depending to a large degree on these effector cells, and that the cyclophosphamide may have affected that ability of using effector cells through lenalidomide and rituximab.
So I think looking at combinations, even beyond single-agent rituximab, with lenalidomide, need to be done very carefully and done within the context of clinical trials and not out there in clinical practice.
In follicular lymphoma, this also appears to be a very active combination. The data from Nathan Fowler in the relapsed setting seem to indicate that the combination of lenalidomide and rituximab is quite active and is now moving forward into randomized trials in the front-line setting. And I think it remains to be seen how this will compare to chemotherapy-based approaches.