Treatment-free survival to bortezomib combined with dexamethasone in patients with refractory/relapsed pure red cell aplasia: a prospective clinical study

硼替佐米联合地塞米松治疗难治性/复发性纯红细胞再生障碍性贫血患者的无治疗生存期:一项前瞻性临床研究

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Abstract

BACKGROUND: Immunosuppressive treatments induce and maintain remissions in a majority of patients with acquired pure red cell aplasia (aPRCA); however, salvage therapy for non-responders remains unsatisfactory. METHODS: In this prospective, open-label, clinical trial (NCT04423367), patients with refractory/relapsed aPRCA were recruited and received subcutaneous bortezomib at 1.3 mg/m(2) in combination with dexamethasone 40 mg weekly(BD regimen) for 12 weeks. The primary endpoint was the overall response rate at 12 weeks. RESULTS: In total, 18 patients were enrolled, including 10 (55.6%) with primary aPRCA and 8 (44.4%) with plasma cell dyscrasia-associated aPRCA. The overall response rate and complete response rate were 61.1% and 55.6%, respectively. Intensive short-term BD regimen led to rapid response, with a median time to response of 40 days (range 21-77 days). Extended maintenance was unnecessary after the 12-week treatment. At a median follow-up of 16.5 (6-51) months, the median treatment-free survival (TFS) was 7 (2-48) months. There was no significant difference in the overall hematological response rate between primary and secondary aPRCA (60% vs. 62.5%, p = 0.914). Adverse events were recorded in 5 patients, including infection, deep venous thrombosis, hyperglycemia, constipation, and liver injury. CONCLUSION: The BD regimen may serve as an effective second-line therapy for refractory/recurrent/intolerant aPRCA patients, with manageable adverse events and possibly longer TFS.

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