Favorable response to second-line sirolimus regardless of STAT3/5b status in acquired pure red cell aplasia: A retrospective study from a single center.

BACKGROUND

Cyclosporine A (CsA) is the standard first-line treatment for acquired pure red cell aplasia (PRCA), but outcomes vary. Effective salvage strategies for CsA-refractory patients, particularly those with complex secondary subtypes, remain inadequately defined. Additionally, the clinical utility of STAT3/5b mutations in guiding treatment selection remains unclear.

OBJECTIVES

To evaluate the efficacy of second-line sirolimus for the treatment of PRCA and explore the possible genetic predictors for the response.

DESIGN

This study was a retrospective, single center, comparative study.

METHODS

Patients with acquired PRCA treated between 2021 and 2025, including 36 patients who received first-line CsA and 22 patients who switched to sirolimus due to lack of response or intolerance. Clinical outcomes, including overall response rate (ORR) and time to response (TTR), were compared between primary and secondary PRCA. STAT3/5b mutation status was also analyzed to assess its predictive value for treatment response.

RESULTS

The ORR for first-line CsA was 25.0% (9/36), with significantly higher efficacy observed in primary cases (42.1%, 8/19) than in secondary cases (5.9%, 1/17; p = 0.015). In the salvage sirolimus group, the ORR was 54.5%, demonstrating efficacy in both primary (37.5%, 3/8) and secondary cases (64.3%, 9/14). The median TTR did not differ significantly between sirolimus and CsA (3.0 vs. 1.5 months, p = 0.150), and both agents achieved sustained remission in responders. Regarding genetic predictors, no responses to CsA were observed in patients harboring STAT3/5b mutations (0/6). In contrast, sirolimus elicited responses in both mutated (3/6) and wild-type (4/5) patients, indicating efficacy irrespective of STAT3/5b status.

CONCLUSIONS

CsA is effective in primary PRCA, whereas sirolimus demonstrates efficacy in both primary and secondary cases regardless of STAT3/5b status. Early genetic profiling may facilitate the identification of patients who may not fully response to CsA and potentially earlier transition to sirolimus salvage therapy.