Melanoma

.

• 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.