Gary J. Schiller, MD: Moxetumomab pasudotox is generally a safe drug. It has one prominent side effect, and that is capillary leak syndrome. The other potential risk is vascular toxicity. Vascular toxicity can be manifest as hemolytic uremic syndrome [HUS], and this is probably a result of the toxin attached to the monoclonal antibody. So these two side effects do need to be carefully evaluated in patients who are on treatment.

Leslie Andritsos, MD: The label does contain two black box warnings for both capillary leak syndrome and hemolytic uremic syndrome. Those were both seen in the early clinical trials of moxetumomab. The capillary leak syndrome occurs a little bit more frequently: about 30% to 35% of patients will develop that, whereas fewer patients will develop hemolytic uremic syndrome. But both of these are very significant side effects occurring in the setting of moxetumomab.

The capillary leak syndrome is treated both with prevention and treatment. The preventive measures are administration of IV [intravenous] fluids, both before and after drug administration, as well as patients being instructed to drink two to three liters of fluid a day during their treatment period, which is days one, three, and five of a 28-day cycle. This is a lot of fluid for patients to drink, but in the clinical trials they were able to do it, and that did help quite a bit with maintaining a patient’s blood pressure and renal function.

Patients who had capillary leak syndrome that was only grade 1 or 2 were able to restart therapy and typically did fine. And it’s important to note that both capillary leak syndrome and hemolytic uremic syndrome can happen at any time of any treatment cycle. They’re both most common in the first eight days of treatment, but they can happen at any time. So these patients do require careful monitoring for the duration of their treatment for either of these toxicities. Patients who develop only grade 1 or 2 capillary leak syndrome can continue with therapy so long as they’re tolerating it, whereas patients with hemolytic uremic syndrome typically, if that toxicity develops, have to discontinue therapy.

There isn’t a specific intervention for HUS outside of supportive care, and it’s recommended that patients are monitored carefully for this with routine CBCs [complete blood counts] to check for new anemia or thrombocytopenia, as well as routine testing for renal function and hemolysis laboratory tests. Patients should have labs done on their treatment days as well as day eight of treatment, and then a mid-cycle monitoring visit.

Patients receiving moxetumomab also may have infusion reactions, and similar to other monoclonal antibody therapies, it is recommended to provide premedications with antihistamines, as well as antipyretics. For patients who have severe infusion reactions, it’s also recommended that steroid premedications are added to their list of premedications with subsequent cycles.

Transcript Edited for Clarity