Hasan Şenol COŞKUN, Ali Murat TATLI, Fatma YALÇIN MUSRI, Sema SEZGIN GÖKSU, Gökhan KARAKAYA, Mustafa Serkan ALEMDAR

İmmün Kontrol Noktası İnhibitörleri ile Tedavi Edilen Malign Melanom Hastalarında Antibiyotik ve Kortikosteroid Kullanımının Tedaviye Etkileri

Amaç: Son yıllarda malign melanom tedavisi tamamen değişmiş, özellikle immün kontrol noktası inhibitörlerinin kullanıma girmesiyle yaşam süresi belirgin olarak uzamıştır. Ancak bu ilaçlar hastaların sadece bir kısmında etkili olabilmektedir. Bu tedavilerden fayda gören hastaların belirlenebilmesi için biyobelirteçler ve tedaviye etki eden faktörler araştırılmaktadır. Çalışmamızda immün kontrol noktası inhibitörü kullanan ileri evre malign melanom hastalarında antibiyotik ve kortikosteroid kullanımının ve hastaların melanom için daha önce adjuvant olarak aldıkları tedavilerin tedavi sonuçları üzerine etkilerini araştırdık. Gereç ve Yöntemler: Çalışmamızda immün kontrol noktası inhibitörleri ile tedavi edilen ileri evre malign melanom hastaları retrospektif olarak tarandı. Yirmidokuz hastanın verilerine ulaşıldı. Hastane kayıtlarından antibiyotik ve kortikosteroid kullanımı ve hastaların daha önce aldıkları adjuvant tedavi verilerine ulaşılarak sağkalım analizleri yapıldı. Bulgular: Yirmidokuz hastanın 18 i %62 antibiyotik kullanımıştı, 16 sında %55 herhangi bir sebeple sistemik kortikosteroid kullanımı vardı. 17 %58,6 hastada adjuvant interferon kullanılmıştı. İstatistiki anlamlılığa ulaşmamasına rağmen tedavi sırasında antibiyotik kullananlarda progresyonsuz sağ kalım PFS ve genel sağ kalım OS daha kısaydı. PFS 9 ay ile 15,9 ay, p= 0,561, OS 18 ay ile 38 ay, p=0,404 . Progresyonsuz sağ kalım ve OS immün kontrol noktası inhibitörleri ile beraber kortikosteroid kullananlarda daha kısaydı PFS 27,2 ay ile 5,4 ay, p=0,007, OS 50 ay ile 14 ay, p=0,009 . Adjuvant dönemde interferon kullanmış olan hastaların metastatik evrede immün kontrol noktası inhibitörleri ile hem pfs hem os sürelerinin daha uzun olduğu görüldü PFS 23,2 ay ile 6.2 ay, p=0,019, OS 39,8 ay ile 12,9 ay, p=0,004 .Sonuç: İleri evre metastatik malign melanom hastalarında immün kontrol noktası inhibitörleri ile beraber antibiyotik ve kortikosteroid kullanımı tedavi sonuçlarını olumsuz etkileyebilmektedir

Anahtar Kelimeler:

İmmün kontrol noktası inhibitörleri, Antibiyotik, Kortikosteroid, İpilimumab, Nivolumab

Impact of Antibiotics and Corticosteroids on The Efficacy of Immune Checkpoint Inhibitors in Patients With Advanced Melanoma

Objective: The treatment of malignant melanoma has changed a lot in recent years. The use of immune checkpoint inhibitors has prolonged survival in patients with advanced melanoma. Our study evaluates the impact of antibiotics, corticosteroids, and adjuvant treatment on the efficacy of immune checkpoint inhibitors in patients with advanced melanoma.Material and Methods: We conducted a retrospective analysis of metastatic melanoma patients treated with ipilimumab and nivolumab. Concomitant antibiotics, corticosteroids for any reason, and prior adjuvant treatment for melanoma were recorded. Progression free survival and overall survival were compared in each group. Results: We enrolled 29 patients with advanced melanoma treated with immune checkpoint inhibitors. Eighteen 62.1% patients had concomitant antibiotic therapy, and 16 55.2% patients had used corticosteroids for any reason. Seventeen patients 58.6% had adjuvant therapy with interferon alpha.Although not significant, PFS and OS were shorter in patients treated with concomitant antibiotics: PFS 15.9 months vs. 9 months, p=0.561; OS 38 months vs. 18 months, p=0.404.PFS and OS were shorter in patients who had used corticosteroids during immune checkpoint inhibitor treatment: PFS 27.2 months vs. 5.4 months p=0.007 and OS 50 months vs. 14 months p=0.009 . PFS was 23.2 months in the adjuvant interferon group vs. 6.2 months with no prior interferon, p=0.019. Overall survival was also longer in patients with prior adjuvant interferon treatment: 39.8 months vs. 12.9 months p=0.004 .Conclusion: Concomitant use of antibiotics and corticosteroids in patients with advanced melanoma may affect the efficacy of immune checkpoint inhibitors

Keywords:

Malignant melanoma Immune checkpoint inhibitors, Antibiotics, Corticosteroids, Ipilimumab, Nivolumab,

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