Eltrombopag is effective in patients with relapse/refractory aplastic anemia—report from a single center in China

Abstract

Eltrombopag has shown a promising effect on patients with refractory/relapsed aplastic anemia (AA). However, data in Asian patients are limited due to the short launching time. Data from relapsed/refractory AA patients treated with eltrombopag in Peking Union Medical College Hospital from December 2017 to May 2019 were analyzed retrospectively. Totally 41 patients including 37 non-severe AA and 4 severe AA were analyzed with a median age of 47 (13~81) years old. The dosage of eltrombopag varies from 25 mg every other day (qod) to 100 mg every day (qd) (median 75 mg qd) with the duration of 13 (3~23) months. The overall response rates were 51.2%, 58.5%, and 55.2% at 3-month, 6-month, and 1-year follow-up. Seventy-five percent of patients achieved the best response below the dosage of 75 mg qd at 3 (1–6) months. Two patients stopped eltrombopag after achieving complete remission and remained stable. Two patients relapsed and evolved to myelodysplastic syndrome. Adverse events included gastrointestinal discomfort, hepatic toxicity, and skin reactions, which were mild and controllable. Eltrombopag is effective for Chinese relapsed/refractory AA patients with a relatively lower dose and acceptable side effects.

Eltrombopag with or without Tacrolimus for relapsed/refractory acquired aplastic anaemia: a prospective randomized trial

“…The correlation between the absolute reticulocyte count and the ORR was also reported in a study on EPAG + ATG+CsA for newly diagnosed SAA patients [ 23 ]. For the EPAG monotherapy group, no influencing factors of the response rate were found, which was consistent with Ruan et al’s study [ 10 ]. Our study did not detect predictors for relapse events in either therapy group, which could be explained by the limited number of relapsed patients, which increased the difficulty of detecting significant differences.…”

“…The AE rate of EPAG+tacrolimus in patients with refractory/relapsed AA was 20% to 30%, which was lower than the AE rate reported in previous studies on EPAG monotherapy for relapsed/refractory AA patients [ 17 , 22 ]. The most common AEs in the EPAG+tacrolimus group and EPAG monotherapy group included dyspepsia and skin pruritus, which were generally consistent with the AEs reported in other studies [ 10 , 16 ], and no severe AEs of CTCAE grades 3-4 were observed.…”

“…For the EPAG+tacrolimus group, one NSAA patient had monosomy 7 at the 12 th month, one SAA patient had a low-risk evolution event (trisomy 8) at the 13 th month but did not progress to MDS, and one SAA patient progressed to MDS (MDS with low blasts, according to WHO 2022 classification) at the 13 th month of follow-up. One SAA patient in the EPAG monotherapy group had t [ 10 , 11 ] (p12; q21) at the 24 th month of follow-up but did not progress to MDS. An increase in PNH clone size occurred in 3 (3.9%) other patients in the EPAG+tacrolimus group at the 5th or 6th month of follow-up: one patient’s PNH clone size increased from 5% to 33%, one from 0% to 4%, and one from 0% to 3%.…”

“…From May 2020 to November 2021, patients with relapsed/refractory acquired AA who came to Peking Union Medical College Hospital (PUMCH) were enrolled according to the following criteria: (1) age ≥14 years old; (2) established diagnosis of acquired AA [ 2 ] after a complete workup, including bone marrow biopsy, cytogenetic examination, autoimmune antibody testing, virus infection history and screening for myelodysplastic syndrome (MDS)-associated genetic mutations; (3) classification of SAA or non-severe AA (NSAA) but with at least one of the following: (A) an absolute neutrophil count <0.5 × 10 9 /L, (B) a haemoglobin level <90 g/L, and (C) a platelet count <30 × 10 9 /L before enrolment [ 10 ]; and (4) previous standard IST, namely CsA + ATG or CsA alone for at least 6 months, but relapsed or failed to respond. Patients meeting any of the following criteria were excluded: (1) specific tests indicating congenital AA (e.g.…”

“…EPAG, a thrombopoietin receptor agonist (TPO-RA), was reported to be efficient for treating AA. The overall response rate (ORR) to EPAG monotherapy was 50%-80% in treatment-naïve moderate AA patients [ 5 ], and 35%-60% in refractory/relapsed AA patients [ 10 , 11 ]. In addition, Townsley et al [ 12 ] found that EPAG combined with IST can improve the ORR of untreated SAA patients to 94%, and a phase-3 trial focused on SAA patients reported a higher complete response rate (CRR) to EPAG + IST therapy than to IST as first-line therapy [ 13 ].…”