Immune Checkpoint Inhibitor-Induced Pure Red Cell Aplasia: A Review of 2 Cases in Metastatic Melanoma.

BACKGROUND Immunotherapy is a novel treatment offering an alternative to traditional chemotherapeutic agents for different malignancies. Hematologic adverse reactions (HARs) related to immune checkpoint inhibitors (ICIs) are uncommon. Pure red cell aplasia (PRCA) is a rare hematologic complication of ICI therapy in metastatic melanoma with significant mortality risk despite treatment with steroids or immunosuppressive therapy. For unexplained acute anemia after exclusion of other causes, performing bone marrow biopsy is imperative to diagnose PRCA and rule out involvement of bone marrow by primary tumor. HARs can occur during ICI therapy or even after ICI therapy is stopped. ICI rechallenge, even after the development of HARs, is considered in some patients with good response to treatment of HARs from ICIs. Recurrence of HARs with the same or different type of reaction is seen in some patients. CASE REPORT Two cases of ICI-induced PRCA were confirmed on bone marrow biopsy after dual ICI treatment with nivolumab and ipilimumab in metastatic melanoma. In case 2, PRCA was successfully treated with steroids and later rechallenged with single-agent nivolumab, causing mild ICI-induced immune thrombocytopenia, which did not require treatment with steroids. CONCLUSIONS It is crucial to increase clinician awareness of the possibility of PRCA development not only during treatment with ICI but also after finishing treatment with ICI; there is high mortality associated with missing an opportunity to diagnose and treat PRCA on time with favorable results. ICI rechallenge can be considered in patients who showed response to immunotherapy, especially those with limited alternative therapeutic options.

"Heart in DRESS": Cardiac Manifestations, Treatment and Outcome of Patients with Drug Reaction with Eosinophilia and Systemic Symptoms Syndrome: A Systematic Review.

Cardiac involvement in drug reaction with eosinophilia and systemic symptoms (DS) is rare but associated with high mortality. The aim of this research was to systematically review case reports by PRISMA guidelines in order to synthetize the knowledge of cardiac manifestations of DS. We identified 42 cases from 36 case reports. Women were two times more affected than men. Two-thirds of patients had cardiac manifestation in the initial phase of the disease, while in one-third of cases cardiac manifestations developed later (mean time of 70 ± 63 days). The most common inciting medications were minocycline (19%) and allopurinol (12%). In 17% of patients, the heart was the only internal organ affected, while the majority (83%) had at least one additional organ involved, most commonly the liver and the kidneys. Dyspnea (55%), cardiogenic shock (43%), chest pain (38%), and tachycardia (33%) were the most common cardiac signs and symptoms reported. Patients frequently had an abnormal ECG (71.4%), and a decrease in left ventricular ejection fraction was the most common echocardiographic finding (45%). Endomyocardial biopsy or histological examination at autopsy was performed in 52.4%, with the predominant finding being fulminant eosinophilic myocarditis with acute necrosis in 70% of those biopsied. All patients received immunosuppressive therapy with intravenous steroids, while non-responders were more likely to have received IVIG, cyclosporine, mycophenolate, and other steroid-sparing agents (60%). Gender and degree of left ventricular systolic dysfunction were not associated with outcomes, but short latency between drug exposure and the first DRESS symptom onset (<15 days) and older age (above 65 years) was associated with death. This underscores the potential importance of heightened awareness and early treatment.