Dr Nooka on the Utility of Iopofosine I 131 in Waldenström Macroglobulinemia

Ajay K. Nooka, MD, MPH, FACP, professor, director, Myeloma Program, Department of Hematology and Medical Oncology, scientific director, Winship Data and Technology Applications Shared Resource, associate director, Clinical Research, Winship Cancer Institute, Emory University School of Medicine, discusses the rationale for investigating iopofosine I 131 (CLR 131) in the phase 2 CLOVER-WaM trial (NCT02952508) in patients with heavily pretreated, multi-class–refractory Waldenström macroglobulinemia (WM).

Nooka begins by elucidating the significance of iopofosine. This agent constitutes a radioactive iodine and is integral to the concept of phospholipid drug conjugates, he states. Investigators are employing various treatment strategies wherein the drug can be directly targeted to cancer cells, exploiting this mechanism, Nooka says. Certain treatments using this approach involve packing the drug into lipids, enabling specific delivery to cancer cells, which readily take up the drug, he explains. One notable example of a lipid-packed regimen is the combination of daunorubicin/cytarabine (Vyxeos) for patients with acute myeloid leukemia, Nooka reports.

Similarly, within the context of WM, the CLOVER-WaM trial, a pivotal expansion portion of the CLOVER-1 trial, is evaluating iopofosine I 131 as a means of delivering a radioisotope directly to cancer cells, Nooka expands. This is achieved by binding iodine-131 to phospholipid ethers on the cancer cell surface, facilitating uptake by the cancer cell, he relays. As such, this phospholipid drug conjugate can be administered directly to the cancer, minimizing toxicity to surrounding healthy cells, Nooka explains. This mechanism represents a novel and innovative approach to achieving desired tumor responses by specifically targeting cancer cells and simultaneously sparing surrounding tissue from off-target adverse effects, he imparts.

This innovative treatment approach has demonstrated promising results, particularly in B-cell malignancies and specifically in WM, Nooka elucidates. Initial results from the CLOVER-1 trial showed promising response rates in the first few enrolled patients, prompting the expansion of the CLOVER-WaM trial within the WM population, he concludes.

Notably, in 2020, the FDA granted a fast track designation to iopofosine I 131 for patients diagnosed with WM who have undergone at least 2 prior therapies, based on data derived from the CLOVER-1 study.