Anti-CD22 Therapy in HCL: Moxetumomab Pasudotox



Gary J. Schiller, MD: In the clinical trial of moxetumomab pasudotox, patients were enrolled who had hairy cell leukemia in second relapse, so these were really patients with third-line disease. There also were patients with disease refractory to reinduction therapy, but they had all received at least two prior systemic therapies, at least one of which was a purine nucleoside analog. Probably many of them had had two cycles of purine nucleoside drugs. Patients were treated with moxetumomab. They were given three doses every 28 days on days one, three and five. They usually got less than or equal to six cycles and then their responses were evaluated by a blinded committee. Eighty patients were enrolled. And typical of what I mentioned before, most of them were men and their average age was 60. The durable remission rate was 30%. The complete remission rate was higher, it was 41%. And the objective response rate was 75%, so this represented something fundamentally new.

To me, what’s important is achieving a hematologic response, which is improvement in blood counts. That’s a therapeutic endpoint that’s very important for me, and 80% of the patients got there. There were 64 patients who got that. Moxetumomab is an immunoconjugate. We now have quite a few drugs in our therapeutic armamentarium in hematologic malignancy and even in solid tumor oncology as well. There are monoclonal antibodies either with or without a payload. In this case, the immunoconjugate has a pseudomonas exotoxin that’s attached, and so this is like a smart bomb directed to a common B-cell antigen expressed in a number of B-cell malignancies, including hairy cell leukemia. And so the monoclonal antibody delivers a toxin designed actually at disconnecting and disabling cellular machinery, important to protein synthesis, and that’s how it delivers its toxic payload and induces apoptosis and cell death of members of the clone.

Leslie Andritsos, MD: Patient selection for moxetumomab pasudotox is really dependent on comorbidities because we know that older patients tend to have more toxicities, especially people over the age of 65. And patients who have baseline renal dysfunction may experience worsening of that, and so particularly patients with a creatinine clearance less than 30 should not receive moxetumomab. In addition to that, any patient with difficulty handling IV [intravenous] hydration, such as people with a low ejection fraction, may not tolerate the infusion cycle. So even though it is a highly effective therapy for relapse and refractory hairy cell leukemia, there are going to be some patients who won’t be able to receive it.

Gary J. Schiller, MD: Now you have a drug whose label is fairly well defined. Moxetumomab’s label is defined by the pivotal trial. And so you don’t have access to that drug in first-line or even in second-line. I think the big question for those of us who treat hairy cell leukemia is how, after two lines of prior therapy, we sequence subsequent drugs. We’ll have moxetumomab, which is FDA approved within this space, but there’s also going to be the consideration of BRAF inhibitors because BRAF is so highly expressed in hairy cell leukemia.

Transcript Edited for Clarity

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