Effective Treatment of a Melanoma Patient with Hemophagocytic Lymphohistiocytosis after Nivolumab and Ipilimumab Combined Immunotherapy.

Immune checkpoint inhibitors have significantly improved the prognosis of melanoma patients. However, these therapies may trigger unexpected immune-related adverse events (irAEs), which are challenging in making the proper diagnosis and providing treatment. Hematological toxicities are possible irAEs, but were poorly evaluated in clinical trials and treatment recommendations of this specific complications are limited. We present a stage IV melanoma patient who developed an extremely rare toxicity - hemophagocytic lymphohistiocytosis (HLH) after the 4th course of combined immunotherapy with nivolumab and ipilimumab. The patient was steroid resistant and only the treatment with various immunosuppressive agents provided control of the disease and finally melanoma regression. In this report, we evaluated the methods of HLH treatment and described our modification of available protocols. Immediate immunosuppression can be life-saving and due to rarity of this condition as well as lack of specific recommendations, every report is valuable for clinicians, especially when treatment was effective.

Cancer care for Ukrainian refugees during the first 6 weeks of 2022 Russian invasion - An experience of a cancer reference centre in Poland.

BACKGROUND: On 24th of February 2022, Ukrainian cancer patients had to face a new war. Here we describe an experience of the Maria Sklodowska-Curie National Research Institute of Oncology Branch Krakow in providing cancer care for Ukrainian refugees during the initial 6 weeks of war. We present patients' characteristic, point out the main challenges and share initiatives undertaken. MATERIALS AND METHODS: For this cross-sectional analysis, we have gathered demographic and clinical data together with date of crossing the Polish-Ukrainian border for 112 Ukrainian refugees with cancer who had their first-time oncology consultation between 24th February and 8th April 2022. We have also implemented national guidelines and created local procedures, interventions and policies to manage this situation. RESULTS: The peak of patient inflow was the third week of War and refugees accounted for 13% of all first-time patients within that period of time. The majority of refugees were women (86%), treated radically (57%) with breast cancer (43%). Most of the patients required systemic treatment (67%). Amongst the main challenges at the time were differences in the reimbursement system, communication issues, lack of patients' documentation or tissue samples, prolonged diagnostic or treatment interruptions, increased risk of COVID-19 infections, chemotherapy side effects, and lack of procedures. Legal, procedural and organizational steps implemented at the local and national level were described. CONCLUSIONS: The Russian invasion on Ukraine forced an unexpectedly high number of Ukrainian cancer patients to seek help abroad, leading to the straining of the health care system in Poland.

Biomarkers of Trastuzumab-Induced Cardiac Toxicity in HER2- Positive Breast Cancer Patient Population.

Trastuzumab-induced cardiotoxicity (TIC) can lead to early treatment discontinuation. The aim of this study was to evaluate: N-terminal brain natriuretic peptide (NT-proBNP), creatine kinase-MB (CK-MB), myoglobin, and selected biochemical and clinical factors as predictors of TIC. One hundred and thirty patients with HER2-positive BC receiving adjuvant trastuzumab therapy (TT) were enrolled. Measurement of cardiac markers and biochemical tests as well as echocardiography were performed prior to TT initiation and every three months thereafter. Cardiotoxicity leading to treatment interruption occurred in 24 patients (18.5%). While cardiotoxicity caused early treatment discontinuation in 14 patients (10.8%), the TIC resolved in 10 (7.7%) and TT was resumed. The most common complication was a decrease in left ventricular ejection fraction of more than 10% from baseline or below 50% (7.7%). In patients with TIC, there was no increase in the levels of NT-proBNP, myoglobin, and CK-MB. BMI, hypertension, ischemic heart disease, diabetes, age, cancer stage, type of surgery, use of radiotherapy, chemotherapy, and hormone therapy were shown to not have an effect on TIC occurrence. NT-proBNP, myoglobin, and CK-MB are not predictors of TIC. There is an ongoing need to identify biomarkers for TIC.

Early Effects of Nivolumab and Ipilimumab Combined Immunotherapy in the Treatment of Metastatic Melanoma in Poland: A Multicenter Experience.

Nivolumab and ipilimumab combination became the first-line standard in advanced melanoma. We assessed its efficacy in a real-life study in Poland. In a one-year follow-up, we evaluated the medical records of 50 melanoma patients treated with that modality in five oncology centers. We recorded therapy outcomes and adverse events (AEs) after 3 and 12 months of therapy. At the first checkpoint, the disease control rate (DCR) was recorded in 58% (n = 29) of patients, but the same number of patients (n = 29, 58%) stopped immunotherapy due to disease progression (PD, n = 14, 48.3%), toxicity (n = 11, 37.9%) or death (n = 4, 13.8%). Among patients with DCR after the induction phase, 8 (27.6%) terminated due to toxicity, and 21 (72.4%) continued. However, at the 12-month checkpoint, only 14 patients (27% of all) were still receiving immunotherapy. In 7 (33.3%) it was discontinued due to PD (n = 2), toxicity (n = 2, 28.6% each), or death (n = 3, 42.9%). AEs occurred in 66.7% (n = 34) of patients; severe (grade 3 or 4) in half of them. Interestingly, those with AEs had an 80% lower risk of death (hazard ratio [HR] 0.2, 95% confidence interval [CI] 0.07−0.57, p = 0.001) and PD (HR 0.2, 95%CI 0.09−0.47, p < 0.0001). In the entire group of patients, after a 12-month follow-up, the median overall survival was not reached (NR, range: 6.8 months-NR) and progression-free survival was 6.3 (range: 3-NR) months. Our results demonstrate that combined immunotherapy is less effective in real-life than in pivotal trials. However, early responders will likely continue the therapy after a one-year follow-up. AEs occurrence might be a predictor of clinical effectiveness.