New Biological Insights and Recent Therapeutic Advances in the Management of Acute and Chronic Leukemias and Myelodysplastic SyndromesClinical implications of the CLL11 trial of obinutuzumab/chlorambucil in patients with untreated CLL and comorbidities
3:10 minutes.
TRANSCRIPTION:
DR BROWN: This was the CLL11 study, the German CLL study group, which led to the registration of obinutuzumab and chlorambucil. And it was a 3-arm study in which patients with comorbidities were randomized to either chlorambucil single agent, rituximab/chlorambucil or obinutuzumab/chlorambucil. And there are multiple stages of comparisons. The one that I think was probably most interesting to people was the direct comparison of obinutuzumab/chlorambucil versus rituximab/chlorambucil. And in that, it was found that the obinutuzumab/chlorambucil improved the complete remission rate, MRD negativity and progression-free survival compared to rituximab/chlorambucil. And we were talking about a year improvement, 27-month progression-free survival for obinutuzumab/chlorambucil versus 15 months for rituximab/chlorambucil. There was also, for obinutuzumab/chlorambucil compared to chlorambucil alone, an overall survival benefit, but that’s compared to chlorambucil alone. The difference with rituximab/chlorambucil was not significant for overall survival at present. DR LOVE: One of the issues here is, it’s always difficult to judge the magnitude of a benefit. You see numbers in a trial and then you see a patient in front of them. And, I mean, I’ve heard different reactions to these data, but I’m just kind of curious, Jennifer, what your thoughts are in terms of what you think this really means clinically. DR BROWN: I think part of the reason I find the data impressive is that my personal experience with obinutuzumab has been impressive. Partly I thought that a priori it was more likely to work better in CLL, because of its ability to directly kill CLL cells, as well as the enhanced ADCC. So a priori, from the in vitro data, I thought it looked promising. And then my clinical experience has been that you get extremely rapid clearance of disease and much deeper responses that I haven’t seen anything similar to with rituximab. And so that has made me inclined to believe the data. DR LOVE: Just getting back to this issue of infusion reaction, Jennifer, I have heard general oncologists express concern about that in the older patient, for example. It has to be balanced out against the hope for efficacy benefit. What’s your actual clinical experience? And when you see a patient’s 85, 90, but otherwise healthy, do you have any concerns about using the drug? DR BROWN: So my clinical experience has been that the infusion reactions are pretty manageable. You can run into trouble with rituximab infusion reactions if you’re not careful, too. And they’re actually different. One thing about obinutuzumab is they’re highly predictable: their first dose, first hour of the infusion. And if you get through that, you’re going to be okay. And so you don’t end up getting late severe reactions, which occasionally turn up with rituximab. And so in that sense, it’s predictable. You definitely have to use highly potent corticosteroids as premedication, and that makes a huge difference. Sometimes I’ll even start steroids, a dose the night before, which I find also can help. But I do that with people at high risk for rituximab reactions, too. So I haven’t, in my personal experience, seen a marked problem that is outside what I’ve managed before with rituximab. |