Dr Castillo on Ongoing Areas of Investigation in Waldenström Macroglobulinemia

Jorge J. Castillo, MD, clinical director, Bing Center for Waldenström Macroglobulinemia, institute physician, Dana-Farber Cancer Institute, associate professor of medicine, Harvard Medical School, discusses the ongoing investigation into potential treatment options for patients with Waldenström macroglobulinemia, including iopofosine I-131 (previously CLR 131).

In the treatment of patients with Waldenström macroglobulinemia, there are several highly effective and safe regimens available, Castillo begins. Presently, the standard approaches involve either chemoimmunotherapy or BTK inhibitors. However, for patients who have undergone prior exposure to both chemoimmunotherapy and BTK inhibitors, determining the optimal third-line treatment remains uncertain, he explains. In this context, there are various options worth considering. Pirtobrutinib (Jaypirca), a noncovalent BTK inhibitor, demonstrated promising efficacy based on previous data that were presented at the 2022 ASH Annual Meeting, with patients benefiting from this approach, Castillo says. Additionally, venetoclax (Venclexta), has shown efficacy in this setting, with encouraging a progression-free survival.

Castillo goes on to explain that other agents are currently under investigation, such as iopofosine, Castillo states. Iopofosine is a novel phospholipid drug conjugate which received fast trackdesignation from the FDA for Waldenström macroglobulinemia A in May 2020. This agent is administered intravenously over 4 infusions within a 71-day interval, and final results from the CLOVER-WaM trial (NCT02952508) are eagerly anticipated, Castillo emphasizes.

Furthermore, additional agents, such as BTK degraders, constitute another category of interest and work differently than BTK inhibitors by attaching to the molecule in an alternative manner to block BTK signaling, Castillo continues. Notably, they appear effective even in patients who have received covalent and noncovalent BTK inhibitors, emphasizing their critical role. Another facet of research involves immunotherapy, he states.

Looking ahead, the future appears promising with targeted agents and immunotherapy, Castillo expands. Although the extent of their benefits to patients is yet to be fully understood, ongoing investigations in other lymphomas suggest a potential avenue for development, he says. As investigators continue to observe these advancements, the prospect of combining targeted agents with immunotherapy emerges as an area warranting further exploration, Castillo concludes.