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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
- PD1 inhibitors (programed death), PDL1 - ligand tumor, PD1 - on T-cells
- NSCLC --> Nivo superior to dosetaxel
- RCC --> Nivo superior to everolimus
- Hodhkin's Lymphoma --> Nevo 87% resposne.
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