Checkpoint inhibitors by Caroline Robert

mmunotherapy
Presentation by Caroline Robert, on 5th June 2017

History
Ipilimumab
- a subset of pts cured
-re-induction is possible

-adding dacarbazine to ipi- no added efficacy!

Pembrolizumab and nivolumab
Pembro vs ipi - data update -
ORR 42% versus 16%
At 32 months
OS 50 % vs 39%
PFS 31% versus 14 %

Combi ipi+nivo Checkmate 067 update
OS 64% at 2 years vs 59% nivo - not a significant difference for now but researchers hope for a much higher OS on combi in time as data is still not mature.

Adverse effects
acute hypophisitis
pneumonitis
colitis
hypo and hyperthyroidism
increased ALT

-vitiligo is linked with a good response with anti PD1

-it is possible to stop the treatment after Complete Response! 

How long do we have to treat?
Response: 2 years is considered optimal; 10 months after stopping patients are still in remission.

Potential biomarkers

• PDL1- High level -high clinical response- patients with high PDL1  do well on combination but also with nivo alone.
• Mutational load - potential antigens might -not practical for use
• Gut microbiota -promising but not yet practical
• Genetical mutations-

Future
Anti PD1- will be the central drug of many combinations - lots of clinical trials in the following years

The decision to stop the treatment- there is no guaranty that if one stops the treatment, one will stay in remission or will respond again.