Iopofosine I 131 Shows Durable Responses in Waldenström Macroglobulinemia

Updated 12-month follow-up data from the phase 2b CLOVER-WaM study (NCT02952508) of iopofosine I 131 in patients with relapsed or refractory (R/R) Waldenström macroglobulinemia (WM) supported the strong efficacy of the therapy in patients who either had or had not received prior Bruton tyrosine kinase inhibitor (BTKi) therapy, according to a news release.¹

The phospholipid-drug conjugate designed to deliver radioisotope iodine 131 demonstrated an 83.6% overall response rate (ORR) and a 61.8% major response rate (MRR) with a median duration of response (DOR) of 17.8 months. The dataset incorporates a minimum of 12 months of follow-up for all enrolled patients, fulfilling an FDA-requested threshold the company says strengthens its regulatory positioning for an accelerated approval submission and initiation of a confirmatory trial.

“The depth, durability, and consistency of responses observed across both the total population and BTKi-treated subsets underscore iopofosine’s potential as a meaningful new treatment option in WM and differentiate it from currently available therapies,” Jarrod Longcor, MBA, chief operating officer of Cellectar Biosciences, stated in the news release.

Disease Background and Unmet Need

WM is an incurable B-cell malignancy characterized by bone marrow infiltration with clonal lymphoplasmacytic cells producing monoclonal immunoglobulin M. Approximately 1500 to 1900 patients are diagnosed annually in the United States, with an estimated 11,500 requiring treatment in the relapsed or refractory setting. BTKis have become standard of care in frontline WM treatment, but there are currently no FDA-approved therapies for patients progressing on BTKi therapy. Non-FDA–approved salvage regimens are used in more than 60% of patients, and more than half receive the same or similar treatment from a prior line of therapy.

Trial Population and Efficacy

CLOVER-WaM enrolled a heavily pretreated population, with patients having received a median of 4 prior lines of therapy (range, 2 to 15). BTKi exposed-patients made up 71% of the population, and 56% of these were BTKi-refractory, based on results from an earlier data cutoff.²

In the per-protocol study population of 55 patients at 12-month follow-up, key efficacy outcomes included an MRR of 61.8%, ORR of 83.6%, median DOR of 17.8 months, median progression-free survival (PFS) of 13.5 months, a very good partial response or complete response rate of 14.5%, and a disease control rate of 98.2%.¹

Efficacy was consistent across BTKi-exposed and BTKi-refractory subgroups. Among 39 BTKi-exposed patients, MRR was 64.1%, median DOR was 18.2 months, and median PFS was 15.9 months. Among 33 BTKi-refractory patients, MRR was 63.6%, median DOR was 18.2 months, and median PFS was 14.8 months. The company noted that responses deepened during follow-up and that iopofosine I 131 is administered as a fixed-dose regimen of four approximately 30-minute infusions, without continuous therapy.

The earlier May 2024 data cutoff with median follow-up of 8.8 months in 55 efficacy-evaluable patients, had reported an MRR of 56.4% and ORR of 80%, with an estimated 72% of responding patients remaining progression-free at 18 months.²

Safety

Iopofosine I 131 demonstrated a predictable safety profile in the updated dataset. Cytopenias were the most common treatment-emergent adverse events.¹ There were no significant bleeding events and low infection rates below 10%. Non-hematologic toxicities were primarily low grade.

Regulatory Path and Next Steps

The sponsor is preparing an accelerated approval submission to the FDA based on the MRR surrogate end point supported by DOR data and plans to initiate a confirmatory randomized study in a post-first line, post-BTKi population in the fourth quarter of 2026, with PFS as the primary end point. Regulatory submissions are also planned in Europe. Full efficacy and safety results in patients treated immediately following BTKi therapy have been accepted for presentation at the American Society of Clinical Oncology Annual Meeting in Chicago.

REFERENCES

1. Cellectar Biosciences reports positive 12-month follow-up data from phase 2b CLOVER WaM study demonstrating durable responses and efficacy of iopofosine i 131 in R/R Waldenström macroglobulinemia. News release. Cellectar Biosciences. May 5, 2026. Accessed May 5, 2026. https://tinyurl.com/ypy5whuu

2. Ailawadhi S, Gavriatopoulou M, Peterson J, et al. Iopofosine I 131 in previously treated patients with Waldenström macroglobulinemia (WM): efficacy and safety results from the international, multicenter, open-label phase 2 study (CLOVER-WaM™). Blood. 2024;144(suppl 1):861. doi:10.1182/blood-2024-200277