Efficacy of Hetrombopag for Thrombocytopenia in Patients with Idiopathic Multicentric Castleman Disease-TAFRO Subtype

Objective To investigate the efficacy of hetrombopag for thrombocytopenia in patients with idiopathic multicentric Castleman disease(iMCD)-TAFRO(thrombocytopenia, anasarca, fever, reticulin fibrosis, renal dysfunction, and organomegaly)subtype.

Methods Twelve patients with iMCD-TAFRO subtype who received hetrombopag therapy at Peking Union Medical College Hospital from October 2022 to December 2025 were retrospectively included. The primary efficacy endpoints were the rates of complete response(CR; platelet count ≥100×10⁹/L without bleeding)and partial response(PR; platelet count ≥50×10⁹/L and at least twice the baseline value without bleeding)at week 4, 8 and 16 of hetrombopag treatment. Secondary efficacy endpoints included time to initial response, time to platelet peak, platelet count levels, and biochemical response rates of Castleman disease

Results The median patient age was 51.5(38.0, 61.0)years, and 75% of patients had severe disease. Among the 12 patients with iMCD-TAFRO subtype, the overall platelet response rate was 75% at both week 4 and week 8(CR rate 50% and PR rate 25% at both time-points). At week 16, the overall platelet response rate reached 100%(CR rate 75%, PR rate 25%). The median time to initial response after hetrombopag initiation was 32.0(24.8, 72.3)d, and the median time to platelet peak was 86.0(46.5, 126.8)d. Platelet counts were significantly elevated at week 4, week 8 and week 16 compared with baselineall P < 0.017; at week 16: 154.0(97.5, 208.0)×10⁹/L vs. 28.5(19.5, 41.5)×10⁹/L, Z=-3.059, P=0.002.Biochemical response rates of Castleman disease were 50% and 91.7% when platelets rose to ≥50×10⁹/L and ≥100×10⁹/L, respectively. No serious adverse events were observed during hetrombopag treatment. As of March 31, 2026, all patients had discontinued hetrombopag, with platelet counts persistently > 100×10⁹/L.

Conclusions Hetrombopag effectively increases platelet counts in patients with iMCD-TAFRO subtype, with a favourable safety profile. Relapse of thrombocytopenia is uncommon after drug discontinuation, and hetrombopag can provide supportive conditions for the treatment of the primary disease.