Copilot said:

Does Dostarlimab Work for All Cancers?

No. Dostarlimab is effective only for tumors that are:

• Mismatch‑repair‑deficient (dMMR) or
• Microsatellite‑instability‑high (MSI‑H)

These cancers have a high mutation burden, making them more recognizable to T‑cells once PD‑1 is blocked.
[scienceinsights.org], [oncodaily.com]

🎯 Cancers Where Dostarlimab May Work

Dostarlimab (Jemperli) shows clinical benefit in cancers that have dMMR/MSI‑H, including:

Rectal cancer (dMMR subtype)

• The MSK trial showed 100% complete response, but only in dMMR rectal cancer, which is 5–10% of all rectal cancers.
  [scienceinsights.org], [oncodaily.com]

Other dMMR/MSI‑H solid tumors

• Dostarlimab is being studied across multiple dMMR solid tumors (e.g., some endometrial cancers).
• Trials like NCT04165772 include multiple mismatch‑repair‑deficient solid tumors, not just rectal cancer.
  [mskcc.org]

Endometrial cancer

• Dostarlimab already has FDA approval for dMMR/MSI‑H recurrent or advanced endometrial cancer (from public regulatory information; this is consistent with how PD‑1 inhibitors are used).

🚫 Cancers Where Dostarlimab Does Not Work

Dostarlimab does not help the majority of cancers, including:

Most rectal cancers

• Only 5–10% are dMMR.
• It does not work in the 90–95% of rectal cancers that are not genetically dMMR/MSI‑H.
  [oncodaily.com]

Most solid tumors without dMMR/MSI‑H

Tumors with:

• intact mismatch‑repair
• low mutation burden
• immune‑cold microenvironments

…do not respond well to PD‑1 inhibitors like dostarlimab.

Blood cancers

PD‑1 inhibitors generally show limited effect in most leukemias, lymphomas, and myelomas (except specific immune‑responsive subtypes — but dostarlimab is not indicated there).

🧬 Why It Only Works for Certain Cancers

Dostarlimab blocks the immune “off switch” (PD‑1), but the immune system can only attack cancers it can “see.”

dMMR/MSI‑H cancers:

• have lots of DNA mutations
• produce many abnormal proteins (neoantigens)
• become highly visible to activated T‑cells

➡️ This is why they respond dramatically to PD‑1 blockade.
[scienceinsights.org], [biologyinsights.com]

Most other cancers:

• have fewer mutations
• don’t generate enough immune‑visible targets
• remain invisible even if PD‑1 is blocked

🧭 Bottom Line

Dostarlimab is not a universal cancer cure.
It is a precision therapy that works extraordinarily well only in tumors with very specific genetic features — primarily dMMR/MSI‑H cancers.

For patients without those mutations, it behaves like many other PD‑1 inhibitors:
➡️ helpful in some cases, ineffective in many.