Alexey V. Danilov, MD, PhD: The choice between obinutuzumab and rituximab is a discussion between the patient and the physician. In my practice, I would strongly favor obinutuzumab in those patients whom I think would be of highest risk of progression within the first 24 months of the induction therapy. Again, we don’t necessarily know who those patients are. We can’t predict them with certainty. However, patients who have a high FLIPI [Follicular Lymphoma International Prognostic Index] score, advanced stage disease, high LDH [lactate dehydrogenase], or beta-2 microglobulin would be prime candidates for a combination of obinutuzumab and chemotherapy. In this particular case, I would use bendamustine/obinutuzumab.
The flip side of this is that patients who receive obinutuzumab are at high risk of infection, particularly during the maintenance phase of therapy. That’s what I would be discussing with my patients—the increased risk of infections with this agent. I would also consider sometimes treating patients with induction with obinutuzumab/chemotherapy and then not following through with maintenance, but that would not necessarily be how the study was designed.
The safety profiles of obinutuzumab and rituximab are quite similar. Both agents are associated with infusion-related reactions. However, the risk of those reactions would be higher with obinutuzumab, compared with rituximab. I do see cytopenias in patients treated with obinutuzumab more frequently than in patients treated with rituximab. I use this agent both in follicular lymphoma and in chronic lymphocytic leukemia, and the adverse effects are quite similar there. The cytopenias with both of these agents typically tend to be quite transient, however, and I particularly do not use any growth factors. Those patients very rarely require transfusions to maintain the platelet count.
Therefore, both drugs appear very safe. I do warn my patients who I treat with obinutuzumab that infusion-related reactions are very common and will happen frequently. However, they can be quite easy to manage in the infusion room. Furthermore, both drugs are associated with some rare complications, such as delayed neutropenia, as well as progressive multifocal leukoencephalopathy, and this tends to be a class effect of anti-CD20 antibodies. There are no data that one or another puts patients at higher risk.
Carla Casulo, MD: Both of them have infusion-related reactions. However, obinutuzumab does have a higher rate of infusion-related reactions—closer to about 60%, compared with about 45% with rituximab. When you administer obinutuzumab, you would use the same protocol of slow infusion and increase the rate as the patient tolerates it, and then have a protocol in place for addressing any infusion-related reactions, if and when they occur.
However, there is a higher rate of that, so I think you have to use caution with someone in whom there is a history of significant sensitivity to medications, or who has a history of anaphylaxis, or has been treated with rituximab previously and also had a high risk of infusion-related reaction. Those patients may be at higher risk of developing an infusion-related reaction with obinutuzumab.
They’re more likely to occur during the first infusion. They do tend to decrease over time. You can premedicate patients with corticosteroids, Benadryl, or things like that. You can mitigate that over time, but usually, it’s the very first infusion.
A patient who has neutropenia, for example, would have to probably delay their treatment and either get growth factor support, or let some time pass between their treatments—delay treatment, in other words—if they have neutropenia. If someone has anemia and it’s not severe, not grade 3 anemia, you may not necessarily delay treatment for anemia. You might delay for cytopenia, such as thrombocytopenia. The dose-limiting, or treatment-limiting, cytopenias, more often than not, will include neutropenia, which we can handle with either growth factor support or delaying treatment and allowing the patient to recover until their next cycle.
Transcript Edited for Clarity