Promising results of tacrolimus plus dexamethasone for ITP

In the phase 2 TARGET 020 trial, the combination regimen of low-dose tacrolimus plus high-dose dexamethasone provided benefits over high-dose dexamethasone monotherapy in patients with immune thrombocytopenia (ITP). Both the initial response rates and the sustained response rates were significantly higher in the combination therapy arm. Thus, low-dose tacrolimus plus high-dose dexamethasone could be a promising first-line treatment for patients with ITP [1].

Dr Zhuo-Yu An (Peking University People’s Hospital, China) explained that approximately 30% of adult patients with ITP relapses in the first 6 months after the initiation of a first-line therapy. Therefore, first-line therapies that demonstrate long-term effectiveness are needed for patients with this condition. The prospective, multicentre, open-label, randomised, phase 2 TARGET 020 trial (NCT04747080) compared high-dose dexamethasone (40 mg, 4 consecutive days with possible repetition after 14 days) (n=56) with high-dose dexamethasone plus low-dose tacrolimus (3–5 ng/mL, 4 consecutive days with possible repetition after 14 days) (n=48). The rationale for the combination regimen was a dual-target strategy, with dexamethasone targeting abnormal B cells and antibodies to counter increased platelet destruction, and tacrolimus targeting hyperactivated T cells to reduce the impaired maturation of megakaryocytes. In this way, both increased platelet destruction and decreased platelet production may be tackled, argued Dr An. The primary outcome was sustained response at 6 months, defined as a platelet count ≥30x10⁹/L (partial remission) or ≥100x10⁹/L (complete remission), a 2-fold increase of baseline platelets, and no use of rescue medication at follow-up.

The initial response rate was higher in the combination regimen arm than in the monotherapy arm (77% vs 55%). In addition, patients treated with the combination therapy showed fewer relapses than patients treated with dexamethasone monotherapy (19% vs 29%). After 6 months, the sustained response rates were higher in the low-dose tacrolimus plus high-dose dexamethasone treatment group (64.6%) than in the high-dose dexamethasone monotherapy group (64.6% vs 41.1). There was no statistically significant difference in incidence of serious adverse events (SAEs) and treatment-related AEs between both treatment regimens. Treatment was well tolerated, with no patients displaying grade 3 or higher AEs.

The results demonstrate that low-dose tacrolimus plus high-dose dexamethasone could be a promising first-line treatment regimen for patients with ITP. However, larger randomised trials are needed to validate the results of the current phase 2 trial.

1. An ZY, et al. Tacrolimus Plus High-Dose Dexamethasone Versus High-Dose Dexamethasone Alone As First-Line Treatment for Adult Immune Thrombocytopenia: The Phase 2, Open Label, Randomized Trial (TARGET 020). Abstract 13, ASH 2021 Annual Meeting, 11–14 December.

 

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Posted on 4 February, 2022