Iopofosine I 131 Shows Safety, Antitumor Activity in R/R Multiple Myeloma

Iopofosine I 131 (CLR 131) in combination with low-dose dexamethasone demonstrated a favorable safety profile and preliminary clinical activity in 31 patients with heavily pretreated relapsed/refractory multiple myeloma, according to results published in Cancers (Basel).^1,2

In the open-label, multi-institutional phase 1 dose-escalation trial (NCT02278315) evaluating the iodine-131–phospholipid conjugate, patients experienced primarily hematologic toxicities that resolved, with no nonhematologic toxicities of grade 3 or higher. Clinical activity was observed, with 4 of 26 patients (15.4%) with partial responses (PRs) and 22 with stable disease.

“The study demonstrated manageable toxicity with adverse events being essentially limited to cytopenias, encouraging disease control, and evidence of antitumor activity in a heavily pretreated population, supporting the potential of this novel targeted radiotherapeutic in these most fragile patients,” said lead author Sikander Ailawadhi, MD, professor of medicine in the Division of Hematology/Oncology at Mayo Clinic in Jacksonville, Florida, stated in a news release.²

Background and Trial Design

Iopofosine I 131 is a phospholipid-drug conjugate is designed to exploit the selective uptake and retention of phospholipid ethers in lipid rafts, structures markedly overexpressed on malignant cells, to deliver targeted radiotherapy to tumor cells.¹ It is also being evaluated in relapsed or refractory Waldenström macroglobulinemia, where it resulted in high response rates, as well as central nervous system lymphoma and other indications.²

The trial enrolled 33 patients who had relapsed after, or were refractory to, a proteasome inhibitor– or immunomodulatory drug–containing regimen, with a median of 4 prior lines of therapy (range, 2-12); 8 of 31 patients were triple-class refractory, and 58.1% had undergone prior autologous stem cell transplantation.¹

Patients were treated sequentially in single-dose cohorts ranging from 12.5 to 31.25 mCi/m² followed by fractionated-dose cohorts, in which equal doses of 15.63 to 20 mCi/m² were administered 7 days apart, each in combination with weekly low-dose dexamethasone for up to 12 weeks. Each cohort enrolled at least 3 patients in a 3+3 design. Patients received 40 mg dexamethasone weekly starting on the day of iopofosine infusion.

Dosing and Safety Findings

A data monitoring committee determined that 31.25 mCi/m² was the maximum tolerated dose in the single-dose group, whereas 20 mCi/m² administered twice was the highest dose evaluated in the fractionated-dose group, as no fractionated cohort met the prespecified dose-limiting toxicity (DLT) threshold. The recommended phase 2 regimen is a fractionated dose of 15 mCi/m² administered on days 1 and 7, in combination with weekly low-dose dexamethasone.

The most common adverse events (AEs) were cytopenias, including thrombocytopenia (93.5%), lymphopenia (74.2%), anemia (71%), leukopenia (61.3%), and neutropenia (58.1%). Nonhematologic AEs, including fatigue (64.5%), nausea (41.9%), and dyspnea (32.2%), were generally grade 1 or 2 and managed with supportive care. Six patients (19.4%) experienced a DLT, most commonly grade 4 thrombocytopenia lasting longer than 7 days, which occurred in 4 patients; all were managed with platelet transfusions. Median time to hematologic nadir was 34 days after the initial dose, and median time to recovery to grade 2 or better was 21 days postnadir. No cases of myelodysplastic syndrome were reported, and no patients discontinued treatment because of AEs, although 5 discontinued because of disease progression. One death was attributed to rapid disease progression and another to septic shock that was considered unrelated to treatment.

Early Efficacy Findings

Among 26 patients evaluable for efficacy, the overall response rate (ORR) was 15.4%, with 4 patients achieving a PR; all patients achieved at least stable disease, for a clinical benefit rate of 100%. Of the patients who achieved a PR, 2 were triple-class refractory and 1 was penta-drug refractory. Clinical activity was more pronounced among patients who received a higher total administered dose of iopofosine I 131: ORR was 6.3% among patients who received less than 60 mCi as a total dose, compared with 30% among those who received 60 mCi or more. Median progression-free survival (PFS) was 101 days in the overall efficacy cohort (95% CI, 79-not estimable) and was not estimable in the group receiving 60 mCi or more, compared with 98 days in the lower-dose group. Median duration of response was 47 days overall, and longer in the higher-dose group (63 days) than in the lower-dose group (31 days).

The study authors noted that response did not appear to correlate with baseline performance status, cytogenetic risk, or International Staging System disease stage, and that the higher administered doses achieved through fractionated dosing appeared to be associated with improved disease response without a notable increase in AEs.

Broader Development Context

According to Cellectar, the findings support continued development of iopofosine I 131 across multiple B-cell malignancies.² The company noted that the drug's mechanism of action is not dependent on a single molecular target or mutation, and that the FDA has granted iopofosine I 131 breakthrough therapy, 6 orphan drug, 4 rare pediatric drug, and 2 fast track designations across various cancer indications, and the European Medicines Agency has granted it a priority medicines designation.

The study authors concluded that the observed safety and tolerability profile, combined with early evidence of antitumor activity in this heavily pretreated population, supports further clinical development of iopofosine I 131 in relapsed/refractory multiple myeloma, including exploration of repeat-dosing strategies given the demonstrated recovery of treatment-related cytopenias over time.

“Iopofosine I 131 represents a differentiated therapeutic approach for patients with relapsed or refractory multiple myeloma who have limited remaining treatment options,” Ailawadhi added in the news release.

REFERENCES

1. Ailawadhi S, Peterson JL, Oliver K, Longcor J, Callander N. A phase I Trial of iopofosine I 131 and dexamethasone in patients with relapsed/refractory multiple myeloma. Cancers (Basel). 2026;18(13):2044. doi:10.3390/cancers18132044

2. Cellectar Biosciences Announces Publication of Phase 1 Study of Iopofosine I 131 in Peer-Reviewed Journal Cancers. News release. Cellectar Biosciences. July 15, 2026. Accessed July 15, 2026. https://tinyurl.com/z7cfn98y