Iopofosine I 131, a novel radiopharmaceutical, has shown promising efficacy and tolerability in heavily pretreated patients with relapsed or refractory Waldenström macroglobulinemia (WM). Data from the phase 2B CLOVER-WaM trial, presented at the 2024 ASH Annual Meeting, indicate that iopofosine I 131 could offer a valuable treatment option for patients with limited alternatives. The study enrolled patients who had received at least two prior therapies and had symptomatic disease requiring treatment.
The CLOVER-WaM study administered iopofosine I 131 in two cycles, with each cycle consisting of 15 mCi/m2 doses on days 1 and 15. The primary endpoint was major response rate (MRR), defined as partial response or better, according to the modified VIth International Workshop on Waldenström Macroglobulinemia Response Criteria. Secondary endpoints included overall response rate (ORR), treatment-free survival (TFS), duration of response (DOR), and clinical benefit rate (CBR).
Efficacy Results
The modified intent-to-treat (mITT) population, consisting of 55 patients, showed a MRR of 56.4% (95% CI, 42.3-69.7). The ORR was 80%. Notably, in patients with MYD88-wild type disease, the ORR was 81%, and in those previously treated with Bruton’s tyrosine kinase inhibitors (BTKi), the ORR was 72%. The CBR was remarkably high at 98%. With a median follow-up of 8.8 months, the median DOR and TFS were not reached, and an estimated 72% of responding patients remained progression-free at 18 months.
Safety Profile
The safety population of 65 patients experienced any-grade adverse events in 87% of cases. Grade 3 or higher treatment-emergent adverse events (TEAEs) occurring in more than 10% of patients included thrombocytopenia (80%), neutropenia (69.2%), anemia (44.6%), lymphopenia (13.8%), infections (12.3%), and febrile neutropenia (10.8%). One patient death was attributed to bacterial sepsis.
Patient Characteristics and Prior Therapies
The study population had a median age of 70 years, with 73.8% being male. The median number of prior therapies was 4 (range, 2-15). A significant proportion of patients (71%) had prior exposure to BTKi, with 56% being BTKi-refractory. Genotyping revealed that 29% had MYD88-wild type, and 9% had CXCR4-mutated disease.
Investigator Comments
According to Dr. Sikander Ailawadhi from Mayo Clinic, treatment options beyond the initial lines of therapy for Waldenström macroglobulinemia are limited. He noted that iopofosine I 131, a small molecule phospholipid drug conjugate (PDC), is designed for targeted delivery of iodine-131.
Implications for Treatment
These findings suggest that iopofosine I 131 could fill a critical gap in the treatment landscape for heavily pretreated Waldenström macroglobulinemia patients, particularly those who have exhausted other available options. The durable efficacy and manageable safety profile observed in the CLOVER-WaM trial support its potential as a valuable therapy in this challenging patient population.
