PURPOSE: CheckMate 914 is a two-part, randomized phase III trial evaluating adjuvant nivolumab plus ipilimumab (part A) or adjuvant nivolumab monotherapy (part B) versus placebo in mutually exclusive populations of patients with localized renal cell carcinoma (RCC) at high risk of postnephrectomy recurrence. Part A showed no disease-free survival (DFS) benefit for adjuvant nivolumab plus ipilimumab versus placebo. We report results from part B. METHODS: Patients were randomly assigned (2:1:1) to nivolumab (240 mg once every 2 weeks for up to 12 doses), placebo, or nivolumab (240 mg once every 2 weeks for up to 12 doses) plus ipilimumab (1 mg/kg once every 6 weeks for up to four doses). The planned treatment duration was 24 weeks (approximately 5.5 months). The primary end point was DFS per blinded independent central review (BICR) for nivolumab versus placebo; safety was a secondary end point. RESULTS: Overall, 825 patients were randomly assigned to nivolumab (n = 411), placebo (n = 208), or nivolumab plus ipilimumab (n = 206). With a median follow-up of 27.0 months (range, 18.0-42.4), the primary end point of improved DFS per BICR with nivolumab versus placebo was not met (hazard ratio [HR], 0.87 [95% CI, 0.62 to 1.21]; P = .40); the median DFS was not reached in either arm, and 18-month DFS rates were 78.4% versus 75.4%. The HR for DFS per investigator was 0.80 (95% CI, 0.58 to 1.12; P = .19). Grade 3-4 all-cause adverse events (AEs) occurred in 17.2%, 15.0%, and 28.9% of patients with nivolumab, placebo, and nivolumab plus ipilimumab, respectively. Any-grade treatment-related AEs led to discontinuation in 9.6%, 1.0%, and 28.4%, respectively. CONCLUSION: Part B of CheckMate 914 did not meet the primary end point of improved DFS for nivolumab versus placebo in patients with localized RCC at high risk of postnephrectomy recurrence.
- MeSH
- adjuvantní chemoterapie MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- ipilimumab * terapeutické užití aplikace a dávkování škodlivé účinky MeSH
- karcinom z renálních buněk * farmakoterapie chirurgie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru * MeSH
- nádory ledvin * farmakoterapie patologie chirurgie MeSH
- nefrektomie * MeSH
- nivolumab * terapeutické užití aplikace a dávkování škodlivé účinky MeSH
- přežití bez známek nemoci MeSH
- protokoly protinádorové kombinované chemoterapie terapeutické užití škodlivé účinky MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- randomizované kontrolované studie MeSH
- MeSH
- inhibitory kontrolních bodů škodlivé účinky terapeutické užití MeSH
- ipilimumab škodlivé účinky terapeutické užití MeSH
- kolorektální nádory * farmakoterapie genetika imunologie MeSH
- lidé MeSH
- metastázy nádorů farmakoterapie MeSH
- mikrosatelitní nestabilita MeSH
- nivolumab škodlivé účinky terapeutické užití MeSH
- oprava chybného párování bází DNA MeSH
- protokoly protinádorové kombinované chemoterapie škodlivé účinky terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- randomizované kontrolované studie MeSH
BACKGROUND: Non-clear cell renal cell cancers (nccRCCs) are a heterogeneous group of more than 20 different entities, but are rarely included in large, randomized trials. Tyrosine kinase inhibitors with or without immune checkpoint inhibition are considered as a standard of care (SOC), but optimal treatment is not yet defined. We designed the first prospective randomized trial comparing ipilimumab/nivolumab to SOC. PATIENTS AND METHODS: We randomized adult patients with previously untreated advanced or metastatic nccRCC 1:1 to nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for 4 doses followed by fixed dose nivolumab of 240 mg every 2 weeks or 480 mg every 4 weeks or to SOC. Patients were stratified by histology and by IMDC risk score. Central pathology review was mandatory. The primary endpoint was the overall survival (OS) rate at 12 months, secondary endpoints included median OS, response rate, progression-free survival (PFS), safety and quality of life. RESULTS: In total, 157 patients were assigned to receive ipilimumab/nivolumab, and 152 to SOC. The 12-month survival rate was 78% with ipilimumab/nivolumab [95% confidence interval (CI) 71-84%] compared to 68% with SOC (95% CI 60-75%, P = 0.026). Median OS was 33.2 months versus 25.2 months, P = 0.163 [HR 0.81 (0.61-1.099)]. PFS was similar in both arms [HR 0.99 (0.77-1.28)]. The ORR was 32.8% versus 19.3%. No major differences between papillary and non-papillary RCC subtypes were observed for any endpoint. Exploratory analysis showed a significant OS advantage [HR 0.56 (95% CI 0.37-0.86)] associated with a PD-L1 CPS score ≥1. Treatment discontinuation due to toxicity occurred in 27 patients (17%) with ipilimumab/nivolumab and 13 patients (9%) with SOC. CONCLUSIONS: Ipilimumab/nivolumab demonstrated a significantly longer OS at the 12-month milestone and an acceptable toxicity profile. Our results therefore underline a relevant clinical benefit of ipilimumab/nivolumab in previously untreated nccRCC entities compared to current SOC.
- MeSH
- doba přežití bez progrese choroby MeSH
- dospělí MeSH
- ipilimumab * aplikace a dávkování škodlivé účinky MeSH
- karcinom z renálních buněk * farmakoterapie patologie mortalita MeSH
- kvalita života MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory ledvin * farmakoterapie patologie mortalita MeSH
- nivolumab * aplikace a dávkování škodlivé účinky MeSH
- prospektivní studie MeSH
- protokoly protinádorové kombinované chemoterapie * terapeutické užití škodlivé účinky MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- standardní péče MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze II MeSH
- randomizované kontrolované studie MeSH
- srovnávací studie MeSH
PURPOSE: There are limited treatment options for advanced melanoma that have progressed during or after immune checkpoint inhibitor therapy. Intratumoral (IT) immunotherapy may improve tumor-specific immune activation by promoting local tumor antigen presentation while avoiding systemic toxicities. The phase 3 ILLUMINATE-301 study (ClinicalTrials.gov identifier: NCT03445533) evaluated tilsotolimod, a Toll-like receptor-9 agonist, with or without ipilimumab in patients with anti-PD-1 advanced refractory melanoma. METHODS: Patients with unresectable stage III-IV melanoma that progressed during or after anti-PD-1 therapy were randomly assigned 1:1 to receive 24 weeks of tilsotolimod plus ipilimumab or 10 weeks of ipilimumab alone. Nine IT injections of tilsotolimod were administered to a single designated lesion over 24 weeks. Intravenous ipilimumab 3 mg/kg was administered once every 3 weeks from week 2 in the tilsotolimod arm and week 1 in the ipilimumab arm. The primary end point was efficacy measured using objective response rate (ORR; independent review) and overall survival (OS). RESULTS: A total of 481 patients received tilsotolimod plus ipilimumab (n = 238) or ipilimumab alone (n = 243). ORRs were 8.8% in the tilsotolimod arm and 8.6% in the ipilimumab arm, with disease control rates of 34.5% and 27.2%, respectively. Median OS was 11.6 months in the tilsotolimod arm and 10 months in the ipilimumab arm (hazard ratio, 0.96 [95% CI, 0.77 to 1.19]; P = .7). Grade ≥3 treatment-emergent adverse events occurred in 61.1% and 55.5% of patients in the tilsotolimod and ipilimumab arms, respectively. CONCLUSION: Combining IT tilsotolimod with ipilimumab did not significantly improve the ORR or OS compared with ipilimumab alone in patients with anti-PD-1 advanced refractory melanoma.
- MeSH
- dospělí MeSH
- ipilimumab * aplikace a dávkování škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- melanom * farmakoterapie patologie imunologie mortalita MeSH
- nádory kůže * farmakoterapie patologie imunologie MeSH
- oligonukleotidy MeSH
- protokoly protinádorové kombinované chemoterapie * terapeutické užití škodlivé účinky MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
Východiska: Léčba checkpoint inhibitory (immune checkpoint inhibitor – ICI) přinesla v léčbě pokročilého nemalobuněčného karcinomu plic (non-small cell lung cancer – NSCLC) revoluční pokrok. Nemálo pacientů s NSCLC má komorbidní onemocnění. U pacientů, kteří již mají poškozenou funkci ledvin, je třeba věnovat zvláštní pozornost renální toxicitě, což je vzácná imunitně podmíněná nežádoucí příhoda. Ačkoli bylo publikováno několik kazuistik léčby ICI u pacientů s pokročilým NSCLC podstupujících hemodialýzu, informace o léčbě ICI u pacientů s chronickým onemocněním ledvin (chronic kidney disease – CKD) jsou limitované. Případ: Uvádíme zde případ úspěšně léčeného 75letého pacienta s CKD a pokročilým NSCLC. Odhadovaná rychlost glomerulární filtrace na začátku protinádorové léčby byla 40 ml/min/1,73 m2. Byl podán nivolumab a ipilimumab, jednak s ohledem na očekáváný terapeutický účinek a jednak kvůli zamezení nežádoucím účinkům. Ipilimumab byl vysazen 1 rok po zahájení léčby a podávání nivolumabu bylo také ukončeno, a to 2 roky od zahájení léčby kvůli dysfunkci štítné žlázy jako imunitně podmíněnému nežádoucímu účinku. Bez toho, aby se u pacienta zhoršilo CKD, byla možná léčba NSCLC dvěma checkpoint inhibitory po dobu ≥ 3 let. Závěr: Režim nivolumab a ipilimumab se může stát jednou z možností léčby pacientů s NSCLC a současně s CKD. Tento článek by mohl poskytnout návrh léčby budoucích pacientů, u kterých je možné předpokládat podobný průběh.
Background: Immune checkpoint inhibitor (ICI) therapy has brought about a revolutionary advance in the treatment of advanced non-small cell lung cancer (NSCLC). Not a few patients with NSCLC have comorbid diseases. In patients who already have impaired renal function, particular attention must be paid to renal toxicity, a rare immune-related adverse events. Although there have been some case reports of ICI therapy for patients with advanced NSCLC undergoing hemodialysis, information on ICI therapy in patients with chronic kidney disease (CKD) is limited. Case: We show herein a case with a successfully treated 75-year-old male patient with CKD and advanced NSCLC. His estimated glomerular filtration rate at the start of anticancer treatment was 40 mL/min/1.73 m2. Nivolumab and ipilimumab were administered, considering both the expectation of therapeutic efficacy and the avoidance of side effects. Ipilimumab was discontinued 1 year after the start of the treatment, and nivolumab was also terminated 2 years after the initiation of the treatment due to thyroid dysfunction as immune-related adverse event. Without worsening of CKD, the patient was able to control NSCLC with two immune checkpoint inhibitors for ≥ 3 years. Conclusion: Nivolumab and ipilimumab regimen might become one of the options for NSCLC patients with CKD. This report could provide some suggestions for the treatment of future patients who might experience a similar course of the therapy.
- MeSH
- chronická renální insuficience chemicky indukované diagnóza MeSH
- inhibitory kontrolních bodů * farmakologie škodlivé účinky terapeutické užití MeSH
- ipilimumab farmakologie škodlivé účinky terapeutické užití MeSH
- lidé MeSH
- nádory plic farmakoterapie klasifikace MeSH
- nemalobuněčný karcinom plic * farmakoterapie komplikace MeSH
- nivolumab farmakologie škodlivé účinky terapeutické užití MeSH
- PET/CT metody MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- kazuistiky MeSH
IMPORTANCE: There remains an unmet need to improve clinical outcomes in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). OBJECTIVE: To evaluate clinical benefit of first-line nivolumab plus ipilimumab vs nivolumab alone in patients with R/M SCCHN. DESIGN, SETTING, AND PARTICIPANTS: The CheckMate 714, double-blind, phase 2 randomized clinical trial was conducted at 83 sites in 21 countries between October 20, 2016, and January 23, 2019. Eligible participants were aged 18 years or older and had platinum-refractory or platinum-eligible R/M SCCHN and no prior systemic therapy for R/M disease. Data were analyzed from October 20, 2016 (first patient, first visit), to March 8, 2019 (primary database lock), and April 6, 2020 (overall survival database lock). INTERVENTIONS: Patients were randomized 2:1 to receive nivolumab (3 mg/kg intravenously [IV] every 2 weeks) plus ipilimumab (1 mg/kg IV every 6 weeks) or nivolumab (3 mg/kg IV every 2 weeks) plus placebo for up to 2 years or until disease progression, unacceptable toxic effects, or consent withdrawal. MAIN OUTCOMES AND MEASURES: The primary end points were objective response rate (ORR) and duration of response between treatment arms by blinded independent central review in the population with platinum-refractory R/M SCCHN. Exploratory end points included safety. RESULTS: Of 425 included patients, 241 (56.7%; median age, 59 [range, 24-82] years; 194 males [80.5%]) had platinum-refractory disease (nivolumab plus ipilimumab, n = 159; nivolumab, n = 82) and 184 (43.3%; median age, 62 [range, 33-88] years; 152 males [82.6%]) had platinum-eligible disease (nivolumab plus ipilimumab, n = 123; nivolumab, n = 61). At primary database lock, the ORR in the population with platinum-refractory disease was 13.2% (95% CI, 8.4%-19.5%) with nivolumab plus ipilimumab vs 18.3% (95% CI, 10.6%-28.4%) with nivolumab (odds ratio [OR], 0.68; 95.5% CI, 0.33-1.43; P = .29). Median duration of response for nivolumab plus ipilimumab was not reached (NR) (95% CI, 11.0 months to NR) vs 11.1 months (95% CI, 4.1 months to NR) for nivolumab. In the population with platinum-eligible disease, the ORR was 20.3% (95% CI, 13.6%-28.5%) with nivolumab plus ipilimumab vs 29.5% (95% CI, 18.5%-42.6%) with nivolumab. The rates of grade 3 or 4 treatment-related adverse events with nivolumab plus ipilimumab vs nivolumab were 15.8% (25 of 158) vs 14.6% (12 of 82) in the population with platinum-refractory disease and 24.6% (30 of 122) vs 13.1% (8 of 61) in the population with platinum-eligible disease. CONCLUSIONS AND RELEVANCE: The CheckMate 714 randomized clinical trial did not meet its primary end point of ORR benefit with first-line nivolumab plus ipilimumab vs nivolumab alone in platinum-refractory R/M SCCHN. Nivolumab plus ipilimumab was associated with an acceptable safety profile. Research to identify patient subpopulations in R/M SCCHN that would benefit from nivolumab plus ipilimumab over nivolumab monotherapy is warranted. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02823574.
- MeSH
- dlaždicobuněčné karcinomy hlavy a krku farmakoterapie MeSH
- dvojitá slepá metoda MeSH
- imunoterapie MeSH
- ipilimumab škodlivé účinky aplikace a dávkování MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru farmakoterapie patologie MeSH
- nádory hlavy a krku * farmakoterapie MeSH
- nivolumab škodlivé účinky aplikace a dávkování MeSH
- platina MeSH
- spinocelulární karcinom * farmakoterapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- komentáře MeSH
Imunoterapie jako moderní metoda onkologické léčby přináší krom řady benefitů i riziko nežádoucích účinků – tzv. immune-related adverse events (ir-AEs). Ty jsou důsledkem specifického mechanismu účinku, který zasahuje do regulace imunitního systému. Ve většině případů mají nežádoucí účinky imunoterapie reverzibilní charakter. Zejména v indukční fázi léčby může dojít ke vzniku kožní toxické reakce (stupeň I–IV). Zásadním krokem managementu kožní toxicity je včasné zahájení imunosupresivní léčby kortikosteroidy po vyloučení infekční etiologie exantému. Po zvážení poměru risk/benefit lze po zaléčení kožních potíží v imunoterapii pokračovat. Důležitá je znalost této problematiky u lékařů prvního kontaktu, interdisciplinární přístup a edukace pacienta. Níže uvedená kazuistika prezentuje případ pacientky s rozvojem závažného erythema exsudativum multiforme po podání 1. cyklu kombinované imunoterapie (nivolumab + ipilimumab) při léčbě diseminovaného tumoru ledviny.
Immunotherapy as an innovative method of cancer treatment provides not only several benefits but also a risk of adverse effects - so-called immune-related adverse events (ir-AEs). They are the consequence of a specific mechanism of action that intervenes in the regulation of the im- mune system In most cases, the adverse effects of immunotherapy are reversible. Especially during the induction phase, the cutaneuous adverse events (grade I-IV) may occur. A fundamental principle of the management of skin toxicity is the immediate initiation of immunosuppressive treatment with corticoste- roids after the infectious aetiology of exanthema has been excluded. Once the skin toxicity is resolved, it is crucial to consider the risk/benefit ratio and possibly continue with immunotherapy. Awareness about this topic among primary care physicians is very important, as well as interdisciplinary approach and patient education. A case report below presents a development of severe erythema exsudativum multiforme after administration of the first cycle of combination immunotherapy (nivolumab + ipilimumab) during treatment of disseminated kidney cancer.
- MeSH
- erythema multiforme * diagnóza farmakoterapie imunologie MeSH
- fixní kombinace léků MeSH
- hormony kůry nadledvin aplikace a dávkování terapeutické užití MeSH
- hydrokortison aplikace a dávkování terapeutické užití MeSH
- imunoterapie metody škodlivé účinky MeSH
- inhibitory kontrolních bodů škodlivé účinky terapeutické užití MeSH
- ipilimumab aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- léková dermatitida MeSH
- lidé MeSH
- nežádoucí účinky léčiv diagnóza farmakoterapie MeSH
- nivolumab aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- prednison aplikace a dávkování terapeutické užití MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Imunoterapie se za poslední dekádu etablovala do terapeutických algoritmů mnohých solidních nádorů, v čele s maligním melanomem, renálním karcinomem (RCC) a nemalobuněčným karcinomem plic (NSCLC). V současné době je možné aplikovat imunoterapii jak v monoterapii, tak v kombinaci s dalším checkpoint inhibitorem. Avšak v případě použití kombinace dvou checkpoint inhibitorů se dostává do popředí také otázka rizika vyššího výskytu nežádoucích účinků, především v podobě tzv. imunitně podmíněných nežádoucích účinků (irAE). S ohledem na neustále se rozšiřující indikace kombinované imunoterapie v léčbě solidních tumorů vyvstává otázka, zda se mezi sebou jednotlivé nádory liší v incidenci a závažnosti irAE, což je předmětem následujícího sdělení.
Over the last decade, immunotherapy has been implemented into therapeutic algorithms of various solid tumors including melanoma, renal cancer (RCC) and non-small cell lung cancer (NSCLC). Immunotherapy with checkpoint inhibitors can be administered as both monotherapy or in combination with another checkpoint inhibitor. However, the risk of immune-related adverse events (irAE) becomes relevant in combined immunotherapy. The growing number of tumors being treated with immunotherapy rises a question whether there are differences across various tumors in terms of irAR incidence and severity. The aim of this article is to address these issues.
- MeSH
- imunoterapie * metody škodlivé účinky MeSH
- inhibitory kontrolních bodů * škodlivé účinky MeSH
- ipilimumab škodlivé účinky MeSH
- karcinom z renálních buněk farmakoterapie MeSH
- kombinovaná farmakoterapie škodlivé účinky MeSH
- lidé MeSH
- melanom farmakoterapie MeSH
- nemalobuněčný karcinom plic farmakoterapie MeSH
- nežádoucí účinky léčiv diagnóza patofyziologie MeSH
- nivolumab škodlivé účinky MeSH
- protokoly protinádorové kombinované chemoterapie MeSH
- Check Tag
- lidé MeSH
PURPOSE: Nivolumab was approved as adjuvant therapy for melanoma based on data from CheckMate 238, which enrolled patients per American Joint Committee on Cancer version 7 (AJCC-7) criteria. Here, we analyse long-term outcomes per AJCC-8 staging criteria compared with AJCC-7 results to inform clinical decisions for patients diagnosed per AJCC-8. PATIENTS AND METHODS: In a double-blind, phase 3 trial (NCT02388906), patients aged ≥15 years with resected, histologically confirmed AJCC-7 stage IIIB, IIIC, or IV melanoma were randomised to receive nivolumab 3 mg/kg every 2 weeks or ipilimumab 10 mg/kg every 3 weeks for 4 doses and then every 12 weeks, both intravenously ≤1 year. Recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) were assessed in patients with stage III disease, per AJCC-7 and AJCC-8. RESULTS: Per AJCC-7 staging, 42.4% and 57.3% of patients were in substage IIIB and IIIC, respectively; per AJCC-8, 1.1%, 30.4%, 62.8%, and 5.0% were in IIIA, IIIB, IIIC, and IIID. After 4 years' minimum follow-up, the AJCC-7 superior efficacy of nivolumab over ipilimumab in patients with resected stage III melanoma was preserved per AJCC-8 analysis. No statistically significant difference in RFS between stage III substage hazard ratios was observed per AJCC-7 or -8 staging criteria (interaction test: AJCC-7, P = 0.8115; AJCC-8, P = 0.1051; P = 0.8392 ((AJCC-7) and P = 0.8678 (AJCC-8) for DMFS). CONCLUSIONS: CheckMate 238 4-year RFS and DMFS outcomes are consistent per AJCC-7 and AJCC-8 staging criteria. Outcome benefits can therefore be translated for patients diagnosed per AJCC-8.
- MeSH
- adjuvancia imunologická škodlivé účinky MeSH
- ipilimumab škodlivé účinky MeSH
- lidé MeSH
- melanom * farmakoterapie chirurgie MeSH
- nádory kůže * farmakoterapie chirurgie MeSH
- nivolumab škodlivé účinky MeSH
- staging nádorů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
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.
