The Role of CD22-targeted Immunotoxins in HCL

Jae Park, MD: Dr Sitlinger, you can tell us about CD22-targeted immunotoxin, the mechanism, and how it works with moxetumomab?

Andrea Sitlinger, MD: This is now approved in the second line or second relapse. It’s an interesting kind of first-in-class type of drug where it’s fused to a pseudomonas exotoxin, and so once it is digging into the cell, the toxin base inhibits protein synthesis and ultimately triggers apoptosis. There have been several studies, and recently in ASH , they presented data on long-term follow-up with this drug. Patients are having long-term response. We’re still waiting for years out like we have for some of the other drugs, but in patients who are having those earlier relapses, it’s something to consider.

Jae Park, MD: Dr Ravandi, I know you participated in the Kreitman published study. You obviously had good experience with these agents. What are your experiences with these agents efficacy wise?

Farhad Ravandi-Kashani, MD: My experience in hairy cell has been limited. We have treated a couple patients. In terms of hairy cell, as you have seen the reports in publications, it is effective in the approved setting, and that’s the second relapse of patients. Dr Kreitman has shown that in many of these patients, you can get MRD –negative responses. The question of MRD negativity comes back, but in the relapse setting, it’s more useful to have MRD negativity because the patient has already shown that the disease has a tendency to keep coming back. If you’re treating a relapse patient, it might be more prudent to try to achieve an MRD-negative response.

Obviously, the drug has a couple adverse effects that are well publicized. Hemolytic uremic syndrome tends to happen in about to 5% to 10% of patients. Also, capillary leak syndrome requires significant monitoring and asking the patient to drink a lot of fluid during the course of therapy. Other things also need...carefully monitored for hemolytic uremic syndrome, including renal function...during the course of therapy. But again, with monitoring and with appropriate management, these are generally limited in terms of the degree of incidents and are also generally reversible. I do believe there is a need to use aspirin prophylaxis when you get this drug, so then some patients with low platelets, we would need to be a bit careful. Overall, it is an active drug, and it does produce MRD-negative responses. You heard about the long-term follow-up data.

Steven Coutre, MD: I participated in the original trial. It has an interesting history. The first iteration of the drug did cause quite a bit of hemolytic uremic syndrome,...but the patients on that trial...were truly refractory patients. These are patients that you had to demonstrate that after they got cladribine for the fourth time or they didn’t respond at all that they were without treatment options at that time. The drug is quite effective, as Farhad mentioned, quite prolonged responses in that difficult-to-treat population. It clearly has a role.

Jae Park, MD: Can someone talk more specifically about the response rate that has been observed in this particular study or to a particular agent? I know the one benefit of this agent is the MRD negativity, as all mentioned, the deeper response they were getting for patients, which hopefully will lead to more durable remissions and less likelihood of needing another line of therapy. For those who are more familiar with it, any one of you, maybe talk about what CR [complete response] rates we see in this type of patient and then the MRD negativity.

Andrea Sitlinger, MD: With the original trial, 41% of patients achieved a CR, and 27 patients, so 34%, achieved MRD negativity. Of those patients, 30% or 24 patients maintained a remission for more than 180 days. These were the truly refractory patients. These patients have done quite well compared to what they had done with other treatments.

Steven Coutre, MD: There is some anecdotal experience with a few patients being retreated with the drug. These are patients who first got it as an investigational agent, and now that it’s commercially available have been retreated many years later. I have one such patient, for example, who retreated successfully and achieved a nice complete response once again.

Transcript Edited for Clarity