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

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.