Expert: Isatuximab Demonstrates Potential in Treating Immune Cytopenias After Stem Cell Transplant

In an interview with Pharmacy Times®, Mary Naufal, PharmD, MS, BCOP, bone marrow transplant (BMT) clinical pharmacy specialist (CPS) at Memorial Sloan Kettering, discussed red cell aplasia as an immune cytopenia that can occur after allogeneic stem cell transplant, particularly in patients with risk factors such as reduced intensity conditioning or ABO mismatch. Standard treatments, including steroids, IVIG, erythropoietin, and other immunosuppressive agents, often have limited effectiveness or significant adverse effects. Because insurance denied coverage for daratumumab, her team pursued isatuximab through a manufacturer assistance program, and the patient achieved transfusion independence after 8 doses. Naufal noted that the success of this case helped support the launch of a prospective clinical trial investigating isatuximab in this setting.

Pharmacy Times: Can you explain what delayed red cell engraftment is following allogeneic hematopoietic cell transplantation, and how isatuximab was utilized in your case report?

Mary Naufal, PharmD, MS, BCOP: Just a brief overview on red cell aplasia following stem cell transplant. It really falls under the umbrella of immune cytopenias, which is the immune destruction of differentiated hematopoietic cells. This can impact red blood cells and platelets.

Currently, the incidence of immune cytopenias following stem cell transplant can range anywhere from 20% to 40%, and it is more common in patients who are receiving an allogeneic stem cell transplant, reduced-intensity conditioning, or an ABO mismatch. These are all risk factors for patients to develop immune cytopenias.

The therapies that we use for patients who develop this complication have largely been extrapolated from the non-transplant setting. The standard of care is usually high-dose steroids; however, those come with significant side effects and further immunosuppress already immunocompromised patients. Other therapies include IVIG, erythropoietin, calcineurin inhibitors, and B-cell–targeted agents such as bortezomib and anti-CD20 agents.

We have also investigated the use of CD38-targeted antibodies such as daratumumab, and there have been some successful case reports for its use in this setting. Isatuximab is a newer anti-CD38 agent. It is FDA-approved in the relapsed/refractory multiple myeloma setting, but given its similarity in mechanism of action to daratumumab, we decided to use it in our case report.

We landed on it as an alternative because our patient was initially denied insurance coverage for daratumumab. She had a case of pure red cell aplasia following her transplant. We tried different agents with no response, so we wanted to move to daratumumab. When it was denied, we were able to obtain isatuximab under the manufacturer’s care assist program. To our knowledge, this is the first case report to use isatuximab in this setting.

We followed the multiple myeloma administration regimen: weekly dosing for four weeks, then every two weeks. Our patient required eight doses before she became transfusion-independent, and her erythroid precursors increased. That is how we landed on isatuximab in our case report.

Pharmacy Times: How did this case report help pave the way for the clinical trial now underway investigating isatuximab in this setting?

Naufal: I think our successful outcome for this patient, combined with the lack of prospective studies—since most of the data, even for daratumumab, is based on case reports, case series, and retrospective studies—motivated one of our physicians to take the lead in opening a study to look at this prospectively.

Currently, we have enrolled our last patient, and we will be analyzing the data and publishing afterwards. This case served as an incentive to explore the therapy in a prospective fashion so that the data becomes more reliable.