Dr Ailawadhi on Iopofosine I-131 in Waldenström Macroglobulinemia

Sikander Ailawadhi, MD, oncologist, Department of Hematology, CAR T-Cell Therapy Program, Mayo Clinic, discusses how the investigational agent iopofosine I-131 (previously CLR 131) may address unmet needs for patients with Waldenström macroglobulinemia.

Patients with Waldenström macroglobulinemia face several unmet needs, Ailawadhi says. There are currently 2 BTK inhibitor–based regimens approved by the FDA for patients with this disease: zanubrutinib (Brukinsa) monotherapy and ibrutinib (Imbruvica) plus rituximab (Rituxan). However, there are several limitations associated with these regimens. For instance, many patients are not suitable candidates for these agents, and these drugs are not tolerable for all patients. Moreover, some patients experience disease progression after treatment with these agents, and the prolonged, continuous intake of specialty medications often leads to financial burden, Ailawadhi explains. Iopofosine I-131 may address some of these treatment barriers associated with BTK inhibitor–based regimens, Ailawadhi emphasizes. When administered as a maximum of 4 intravenous infusions over 3 months in the phase 2 CLOVER-1/CLOVER-WaM trial (NCT02952508), iopofosine I-131 elicited durable responses.

Furthermore, specific genetic subtypes of Waldenström macroglobulinemia exhibit resistance to available agents, Ailawadhi notes. Preliminary data indicate that iopofosine I-131 has activity across diverse patient populations and is effective regardless of patient characteristics such as prior BTK inhibitor treatment, genetic mutation status, and the number of prior lines of therapy, according to Ailawadhi.

These observations are based on small datasets, and the confirmation of these findings is contingent on more extensive and mature clinical trial data. These include final results from the pivotal expansion cohort of CLOVER-WaM in patients with Waldenström macroglobulinemia who have received at least 2 prior lines of therapy, Ailawadhi says. However, in the context of a rare disease like Waldenström macroglobulinemia, patient needs often align with the inefficiency, intolerability, or costliness of available agents, and many patients require alternative treatments following disease progression on standard drugs, Ailawadhi explains. These patients need additional therapies in the Waldenström macroglobulinemia arsenal to achieve optimal benefit, Ailawadhi concludes.