Dr Ailawadhi on Early Data for Iopofosine I 131 in Waldenström Macroglobulinemia

Sikander Ailawadhi, MD, oncologist, Department of Hematology, CAR T-Cell Therapy Program, Mayo Clinic, discusses implications of early efficacy and safety findings foriopofosine I 131 (CLR 131) in heavily pretreated patients with various B-cell malignancies, including Waldenström macroglobulinemia.

The radiotherapeutic iopofosine I-131 was previously evaluated in the phase 2 CLOVER-1 trial (NCT02952508), where the agent displayed safety and efficacy in heavily pretreated patients with Waldenström macroglobulinemia. Results from this trial supported the CLOVER WaM expansion cohort within the study specifically for patients with Waldenström macroglobulinemia.

Topline data showed that the regimen generated durable responses and was associated with a tolerable safety profile in this patient population, Ailawadhi reports. Among patients with Waldenström macroglobulinemia who had received a median of 4 prior lines of therapy, the overall response rate was 75.6% with iopofosine I 131. Moreover, the regimen produced a major response rate (MRR) of 61% (95% CI, 44.50%-75.80%; 2-sided P < .0001), and a disease control rate of 100%, which exceeded the protocol statistical hurdle of 20%. At a median follow-up of 8 months, the median duration of response (DOR) was not yet reached, the progression-free survival rate was 76%, and the stringent complete remission rate was 8%.

These preliminary results are promising, considering the heavily pretreated patient population included in the trial, Ailawadhi states. Patients were required to have at least 2 prior lines of therapy, and a subset had previously received a BTK inhibitor and either became intolerant to it or progressed on it, he expands. Despite being heavily pretreated, patients achieved high responses with the regimen across various patient subgroups, Ailawadhi reports. Responses were observed regardless of whether patients had prior exposure to a BTK inhibitor, were intolerant to BTK inhibitors, or had high-risk genetic profiles, he adds. Further testing to identify high-risk genetics is underway and will be shared in subsequent analyses, he notes. This indicates a significant benefit across various subgroups of patients participating in the trial, Ailawadhi explains.

Thus far, the regimen's adverse effect (AE) profile appears to be predictable and manageable, Ailawadhi continues. Patients did not experience non–blood count–related AEs such as nausea, vomiting, or diarrhea, he says. Even when platelet and neutrophil counts decreased, fevers were not observed, and these AEs were effectively managed. This predictability allows for proactive management, contributing to the overall safety profile of the treatment, Ailawadhi states.

Further analysis and data sharing are eagerly awaited to validate these initial observations and provide more comprehensive insights into the potential benefits of the treatment, Ailawadhi concludes.