Ianalumab plus Eltrombopag in Immune Thrombocytopenia

Clinical Snapshot

Key Findings

• P Value: P=0.04 (9mg group) and P=0.045 (3mg group) vs placebo

• Effect Size: Hazard ratio 0.55 (9mg group) and 0.58 (3mg group) vs placebo

• Primary Outcome: Freedom from treatment failure at 12 months: 54% (9mg ianalumab) vs 51% (3mg) vs 30% (placebo)

• Nnt Or Sensitivity: NNT approximately 4 patients (based on 24% absolute risk reduction for 9mg group)

• Confidence Interval: 95% CI for 12-month freedom from treatment failure: 39-67% (9mg), 36-64% (3mg), 18-43% (placebo)

Clinical Application

Requires monthly IV infusions for 4 months plus daily oral eltrombopag. Feasible in Australian haematology centres with IV infusion capabilities. Eltrombopag available on PBS for ITP. Ianalumab would require TGA approval and PBS listing. Fits within RACGP/ASH guidelines for second-line ITP management if approved. Adults with primary ITP who have failed first-line glucocorticoid therapy and require second-line treatment

Abstract

BACKGROUND: Current second-line treatments for immune thrombocytopenia (ITP) require long-term administration. Ianalumab, a monoclonal antibody targeting B cells, is being assessed as a short-course second-line therapy in ITP. METHODS: In this phase 3, randomized, double-blind trial, we assigned, in a 1:1:1 ratio, adults with primary ITP and an insufficient response or a relapse after first-line glucocorticoid therapy to receive ianalumab at a dose of 9 mg or 3 mg per kilogram of body weight or placebo once monthly for 4 months. Eltrombopag, an oral thrombopoietin-receptor agonist, was administered once daily in each group according to local prescribing information; the dose was tapered until discontinuation by the end of week 24 in eligible patients. The primary end point was freedom from treatment failure, as determined in a time-to-event analysis, with treatment failure defined by a platelet count of less than 30×109 per liter more than 8 weeks after randomization, initiation of rescue therapy more than 8 weeks after randomization, initiation of new ITP therapy, inability to taper or discontinue eltrombopag because of an inadequate platelet count, or death from any cause, whichever occurred first. The key secondary end point was a stable response at 6 months, defined by a platelet count of at least 50×109 per liter in at least 75% of the measurements between weeks 19 and 25 without use of rescue therapy or new ITP therapy. Safety was assessed. RESULTS: A total of 152 patients underwent randomization: 50 to the 9-mg ianalumab group, 51 to the 3-mg ianalumab group, and 51 to the placebo group. The estimated probability of being free from treatment failure at 12 months was 54% (95% confidence interval [CI], 39 to 67) in the 9-mg group, 51% (95% CI, 36 to 64) in the 3-mg group, and 30% (95% CI, 18 to 43) in the placebo group. The time to treatment failure was significantly longer with ianalumab plus eltrombopag than with placebo plus eltrombopag; the estimated hazard ratio for treatment failure (ianalumab vs. placebo) was 0.55 (P = 0.04) in the 9-mg group and 0.58 (P = 0.045) in the 3-mg group. The percentage of patients with a stable response at 6 months was significantly higher in the 9-mg group than in the placebo group (62% vs. 39%; P = 0.045). The overall frequency of adverse events during the treatment period was generally similar in the three groups. The frequency of serious adverse events was 16% in the 9-mg group, 6% in the 3-mg group, and 4% in the placebo group. CONCLUSIONS: Ianalumab plus eltrombopag led to a longer time to treatment failure than placebo plus eltrombopag. (Funded by Novartis; VAYHIT2 ClinicalTrials.gov number, NCT05653219.).

References

1. 1.Cuker, A., Stauch, T., Cooper, N., Al-Samkari, H., Michel, M., Ghanima, W., Urban, P., Fronczek, J., Foster, M., Weill, M., Zhang, L., Hou, M., Zander, T., Sharif, A., Sun, J., Nath, U. K., Schutgens, R., Rossi, E., Deleu, L., Červinek, L., Yoon, J.-H., Chang, H., Ruchutrakool, T., Iino, M., Goto, T., & Zaja, F. (2026). Ianalumab plus eltrombopag in immune thrombocytopenia. *New England Journal of Medicine*. https://doi.org/10.1056/NEJMoa2515168