Dr Castillo on the Rationale for Evaluating Iopofosine I 131 in Waldenström Macroglobulinemia

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 rationale for evaluating the efficacy of iopofosine I 131 (previously CLR 131) in the phase 2 COLVER WaM trial (NCT02952508) evaluating patients with Waldenström macroglobulinemia.

In Waldenström macroglobulinemia, current treatment options such as chemoimmunotherapy and BTK inhibitors have shown high effectiveness and generated durable responses, Castillo begins. However, as Waldenström macroglobulinemia is an incurable disease, there is a need for additional treatment options, Castillo explains. He adds that this is especially important with patients living longer. The single-arm, multicenter, multinational CLOVER WaM study addresses this need by investigating the use of iopofosine I 131 for patients with relapsed/refractory Waldenström macroglobulinemia who have received at least 2 prior lines of therapy, including BTK inhibitors, Castillo states.

Iopofosine I 131 is a potential first-in-class, targeted radioligand therapy, Castillo continues. It is administered intravenously over 4 doses spaced several months apart, offering a finite treatment course for patients, he details. What sets Iopofosine I 131 apart is its unique mechanism of action compared with existing therapies in Waldenström macroglobulinemia, Castillo says. As a radioisotope and phospholipid-drug conjugate, iopofosine I 131 presents a novel approach that may provide alternative benefits and outcomes for patients with Waldenström macroglobulinemia, he says.

On January 8, 2024, topline data from the CLOVER WaM trial demonstrated 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) with the agent in the efficacy-evaluable population (n = 41).

Moreover, the agent produced a disease control rate of 100% and the median duration of response (DOR) has not yet been reached at a median follow-up of 8 months.

The agent was previously granted fast track designation in 2020 by the FDA for patients with lymphoplasmacytic lymphoma/Waldenström macroglobulinemia.