Melanoma

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    • Dacarbazine (PO
    • Temozolamide (IV)
    • 9mo survival  (5% that are cured)
    • (1% - spontaneous remission)
    • Interferon
    • IL-2
    • Biochemotherapy (decarbazine + IL2)
    • Carbotaxel (doesn't work). 
    • RAS --> RAF --> MEK --> P13 Kinase
      • Vemufinib
      • Dabrafenib
    • CTLA4 monoclonal Antibody
      • CD8 --> allows immune response to coninue
    • Ipilimumab
      • RR 15%
      • 12 weeks to have response
      • Survival 22-29%
      • (The ones that respond, get cured ~ 25%).
      • 30-40% have autoimmune toxocity (colitis, pan-hypopit, rash, hepatitis, vitiligo, thyroid disorders)
        • Prednisone 1mg/kg if toxicity.
        • If doesn't work, use infliximab, or mycophenolate
    • April 2011 --> 
      • PD1 inhibitors (programed death), PDL1 - ligand tumor, PD1 - on T-cells
        • cancer cell uses PD1 to evade immune response (self-signal)
        • Pemberlyzimab (lambomizumab before, but laborghini asked to change)
          • Nivolimumab
        • Take <6w to have response
      • compared Pemberlyzimab to Ipi &* Nivo to Ipi --> far superior (former).
      • Long-term 35-40% survival @3y.
      • ASCO --> Nivo + Ipilimumab --> much higher response.
        • 90% alive at 1y
        • progression free survival improved. 
        • Grade 3-4 toxicity 15% (Nivo)
        • Grade 3-4 toxicity 55% (almost 100% in real world) (nivo + ipi).
      • which patients to treat
        • PDL1 testing on tumor.
        • Correlated somewhat. 
        • PLD1 positive --> treat with Nivo
        • PLD1 negative --> Nivo + Ipi (may have positive tumor closer inside tumor)
      • Ipi 125,000 x4 doses. (125,000)
      • Pembro & Nivo -->  q2-3w x2y (200,000 x2yrs)
      • Combo --> $350,000
    • NSCLC --> Nivo superior to dosetaxel
    • RCC --> Nivo superior to everolimus
    • Hodhkin's Lymphoma --> Nevo 87% resposne.
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