# Successful Control of Chemotherapy-Induced Breakthrough Hemolysis With Ravulizumab in a Patient With Paroxysmal Nocturnal Hemoglobinuria During Carboplatin-Pemetrexed Treatment for Lung Adenocarcinoma

## TL;DR

A patient with PNH and lung cancer successfully managed chemotherapy-induced hemolysis using ravulizumab, allowing continued treatment and extended survival.

## Contribution

Demonstrates effective use of ravulizumab for chemotherapy-induced breakthrough hemolysis in PNH patients undergoing cancer treatment.

## Key findings

- Ravulizumab normalized lactate dehydrogenase and raised hemoglobin levels in a PNH patient.
- Personalized ravulizumab scheduling enabled 14 chemotherapy cycles without transfusion or thrombosis.
- The patient achieved a PFS of two years and five months, exceeding the median for this regimen.

## Abstract

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disorder characterized by complement‑mediated intravascular hemolysis. Although breakthrough hemolysis (BTH) is typically triggered by infections or surgery, chemotherapy-induced BTH is seldom reported, and optimal management strategies during cytotoxic cancer therapy remain undefined. We report a 52‑year‑old man with longstanding PNH who developed stage IVA epidermal growth factor receptor‑mutated lung adenocarcinoma. After discontinuing first‑line osimertinib due to diarrhea, second‑line carboplatin-pemetrexed (chemotherapy regimen consisting of carboplatin and pemetrexed) induced severe BTH, evidenced by lactate dehydrogenase rising to 2,462 U/L and hemoglobin (Hb) dropping to 4.6 g/dL. Introduction of ravulizumab promptly normalized lactate dehydrogenase (<250 U/L), raised Hb to 10.5 g/dL, and suppressed total hemolytic complement activity (<14 U/mL). Although mild hemolysis recurred before subsequent cycles, administering ravulizumab before each chemotherapy session prevented further episodes. The patient completed 14 cycles without transfusion or thrombosis and achieved a progression-free survival (PFS) of two years and five months, far beyond the ~5.5 month median for this regimen. Personalized scheduling of ravulizumab enabled uninterrupted cytotoxic chemotherapy by effectively managing BTH, suggesting that sustained complement C5 inhibition may confer oncologic benefits. Prospective studies are warranted to evaluate the broader impact of complement blockade in patients with PNH and malignancy.