Expert: Isatuximab Rapid Infusion May Improve Efficiency and Patient Experience

In an interview with Pharmacy Times®, Alice Wang, PharmD, BCOP, lymphoma clinical pharmacy specialist at Memorial Sloan Kettering, discussed how isatuximab, a CD38 monoclonal antibody, has expanded from use in relapsed/refractory multiple myeloma to frontline treatment in transplant-ineligible patients. She explained the standard infusion protocol, associated adverse effects, and emerging data supporting the feasibility of rapid infusion, which showed no infusion reactions in both clinical trials and real-world settings. Based on these findings, her institution adopted rapid infusion after two tolerated doses to improve patient convenience, clinic efficiency, and potential economic outcomes.

Pharmacy Times: Can you describe how rapid infusion isatuximab fits into the current treatment landscape?

Alice Wang, PharmD, BCOP: Isatuximab is a monoclonal antibody. Its target, CD38, is expressed highly on plasma cells, which makes it a great target for the treatment of multiple myeloma. It's currently approved for both the relapsed/refractory and frontline settings. Originally, it was for the relapsed/refractory setting in combination with dexamethasone and either carfilzomib or pomalidomide. More recently, it has expanded to frontline use in patients who are transplant-ineligible, in combination with bortezomib, lenalidomide, and dexamethasone. Its use is rapidly expanding.

This medication is given as an IV infusion. It's administered weekly for the first cycle and then every other week for newly diagnosed patients. This transitions to every four weeks starting with the 18th cycle. Notable side effects include neutropenia, other myelosuppression, infections, and infusion reactions. These infusion reactions occur in about a third to half of patients. Most are low-grade, grade one or two, and the majority occur within the first cycle, specifically the first dose.

To mitigate these reactions, the package insert recommends administering premedications before every dose, as well as slowly uptitrating the infusion rate for the first and second doses. The first dose is given over at least three and a half hours. If there are no reactions, the second dose takes a minimum of about two hours, and the third and subsequent doses take 75 minutes.

As we're using this medication more in practice, more interest has come to how we optimize administration. With daratumumab, the “cousin” in this class of CD38 monoclonal antibodies, we saw a transition from traditional titration to rapid infusions and subcutaneous injections. We're seeing the same with isatuximab. There are data on both subcutaneous injection and rapid infusion, but the subcutaneous injection has not been approved yet, so the focus is on rapid infusion.

Our experience with rapid infusion has been summarized in two studies. Briefly, one was a phase 1b study that included about 45 patients. These patients had been on isatuximab for a median of 46 cycles, well beyond the point of risk for reactions. They were transitioned from standard infusion to a rapid infusion over 30 minutes with the standard premedications, and no reactions occurred.

The second was a smaller real-world study from Canada that included 15 patients. These patients had only recently started isatuximab. Nine of the 15 had received only two prior doses, and a handful of others had received four prior doses before being switched to the rapid infusion protocol, again with standard premedications. In these 15 patients, no infusion reactions were noted.

This demonstrates the feasibility of implementing rapid infusion isatuximab.

Pharmacy Times: How have you approached adopting the practice of rapid infusion isatuximab?

Wang: Based on the two trials I shared previously, we became interested in whether it was feasible to adopt this approach at our institution. We started by looking at our current use of isatuximab. Looking back at the past three years, we found about 80 patients who had been receiving isatuximab with over 1300 doses.

We identified about a 30% incidence of infusion reactions, which is in line with what has been reported in the literature. Greater than 90% of these reactions occurred with the first dose, and the remainder occurred with the second dose. There was one outlier—a patient who received the 12th dose and had a reaction—but this occurred after a treatment pause of about four to five months.

Based on this information and the previous data, we were comfortable implementing rapid infusion isatuximab after patients had tolerated two previous doses. Starting with the third dose, we continue the standard premedications. If there is a prolonged delay, we restart with cycle one, day one protocol.

We hope this will improve patient and clinic convenience in administering this medication. We also look forward to reviewing how this protocol impacts infusion rates and the economic impact on both patients and clinics.