PD-1 Blockade in Tumors with Mismatch-Repair Deficiency

[D.ap]

BACKGROUND
Somatic mutations have the potential to encode “non-self” immunogenic antigens. We hypothesized that tumors with a large number of somatic mutations due to mismatch-repair defects may be susceptible to immune checkpoint blockade.


http://www.nejm.org/doi/full/10.1056/NEJMoa1500596

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"First reported case of alveolar soft part sarcoma in constitutional mismatch repair deficiency syndrome tumor spectrum - diagnosed in one of the siblings with constitutional mismatch repair deficiency"

Dear Editor,

DNA mismatch repair (MMR) is a system for recognizing and repairing errors, which occur during DNA replication and recombination. Biallelic deleterious germline mutations in MMR genes (MLH1, MSH2, MSH6, and PMS2) lead to constitutional MMR deficiency syndrome (CMMR-D).[1]

We are reporting two cases of CMMR-D in siblings of a family, who developed acute lymphoblastic leukemia (ALL) with glioblastoma multiforme and ALL with alveolar soft part sarcoma (ASPS) (first case in CMMR-D spectrum) respectively.[2]



https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5379899/

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Breelyn Wilky tweeted


"FDA Approves Pembrolizumab for Microsatellite Instability-High and Mismatch Repair Deficient Cancers "

http://www.onclive.com/web-exclusives/f ... nt-cancers

[Olga]

Can you ask her if it means an approval for sarcomas esp. ASPS?

[D.ap]

Hi Olga,

In talking with doctors, patients and researching it appears that this is great news of FDA approval for those cancers/ sarcomas of congenital origination's, that are determined to be MSI-H ? The testing for MSI is apparently very trustworthy and has been used with colon cancer patients. It was felt that uterine and colon sarcomas/cancers as well as congenital tumor cancers/ sarcomas will be the immediate benefices of the FDA's announcement.
However in reading this article, I feel with improved testing of PD-L1 , that the PD-1 blockade would be the ticket for a lot of ASPS patients.
And what do you think of the term congenital? Is it applicable to ASPS?

IMHO, the beginning would be if we could test the MSI then go from there.