# Immune checkpoint inhibitor-induced pure red cell aplasia: a nationwide retrospective case series and literature review

## TL;DR

This study examines pure red cell aplasia caused by immune checkpoint inhibitors, showing it is a rare but severe side effect that occurs early and responds to steroid treatment.

## Contribution

The study provides a nationwide case series and literature review on ICI-induced pure red cell aplasia, highlighting its clinical features and treatment outcomes.

## Key findings

- ICI-PRCA occurs early, with a median onset of 63 days after treatment initiation.
- Systemic steroids and ciclosporin A are effective in treating ICI-PRCA.
- Rechallenge with ICI led to recurrence in one of four patients.

## Abstract

Immune checkpoint inhibitors (ICIs) may lead to rare but severe hematological adverse events, including pure red cell aplasia (ICI-PRCA). We conducted a nationwide retrospective national case-series and compiled our data with patients from the VigiBase international pharmacovigilance database. We gathered 16 cases of ICI-PRCA Among all the grade ≥ 3 adverse event reported in VigiBase, PRCA was more than two times more reported with ICI compared to all other drugs ROR [IC95%] 2.43 [1.89;3.13]. We identified 15 additional patients in our literature review. Half of the patients were women (52%), median age 63 years (range: 29–90). ICIs were mostly used in melanoma (48%) and lung adenocarcinoma (16%) in metastatic stage (29%). Monoclonal antibody targeting programmed death-1 (PD-1) alone was involved in 61% of cases. The median time from ICI initiation to symptoms onset was 63 days (range: 28–465). Grade ≥3 anemia in found in all cases (100%). Thirteen patients (42%) were treated with corticosteroids as monotherapy with an ORR of 69%. Thirteen patients (42%) required additional therapy. ICI therapy was discontinued in all patients and rechallenge was attempted in 4 patients (13%), with recurrence in one case. ICI-PRCA is a severe and early-onset immune adverse event. Both systemic steroids and cicloporine A seems effective in these immune-related forms.