Jorge J. Castillo, MD, clinical director, Bing Center for Waldenström Macroglobulinemia, institute physician, Dana-Farber Cancer Institute, associate professor, medicine, Harvard Medical School, discusses the efficacy of treatment with iopofosine I 131 (previously CLR 131) in patients with Waldenström macroglobulinemia.
Topline data from the phase 2 CLOVER WaM trial (NCT02952508) were shared on January 8, 2024, showing that the agent elicited an overall response rate (ORR) of 75.6% and a major response rate (MRR) of 61% (95% CI, 44.50%-75.80%; 2-sided P < .0001), meeting the trial’sprimary end point. Furthermore, the disease control rate was 100% and at a median follow-up of 8 months, the median duration of response (DOR) has not yet been reached. Notably, these data continue to support the 2020 fast track designation of iopofosine I 131, which was granted by the FDA to patients with lymphoplasmacytic lymphoma/Waldenström macroglobulinemia.
The data presented on January 8th, 2024, exceeded expectations, Castillo begins. The ORR was also high, and the clinical benefits observed in these patients was substantial, he emphasizes. From a clinical research standpoint, these data support the continued evaluation of therapies to address unmet needs in Waldenström macroglobulinemia, particularly the lack of complete responses (CRs) seen in this disease, he emphasizes. Achieving CRs has been a challenge in Waldenström macroglobulinemia, contrasting with the efficacy of therapies for patients with other hematological conditions, in whom deep responses and minimal residual disease–negative treatment outcomes are more attainable, he states.
In the presented data, an 8% stringent CR rate with iopofosine I 131 was observed, a noteworthy development given that traditional treatments, such as chemotherapy, are the primary inducers of CRs in Waldenström macroglobulinemia clinical trials, Castillo expands.
The efficacy of the regimen is especially interesting considering the targeted patient population, which includes those previously exposed to rituximab (Rituxan)–containing regimens and BTK inhibitors, Castillo continues. This subset of patients has limited treatment options. In the trial, patients underwent a median of 4 prior treatments, according to Castillo. Notably, iopofosine I 131 demonstrated effectiveness in patients regardless of their mutational status, adding an intriguing dimension to this agent’s potential application in clinical practice, he concludes.
