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Dostarlimab immunotherapy gives amazing results in advanced rectal cancer patients

Mismatch repair–deficient, locally advanced rectal cancer was completely treated in 12 patients by  single-agent treatment with dostarlimab (Jemperli, monoclonal antibody) programmed death receptor-1 (PD-1) blockade. 

These patients have undergone at least 6 months of follow-up. All 12 patients (100%; 95% confidence interval, 74 to 100) showed no evidence of tumor on magnetic resonance imaging, 18F-fluorodeoxyglucose–positron-emission tomography, endoscopic evaluation, digital rectal examination, or biopsy.

No patients had received chemoradiotherapy or surgery, and no cases of progression or recurrence had been reported during follow-up (range, 6 to 25 months). Amazingly no adverse events of grade 3 or higher.

JEMPERLI is a programmed death receptor-1 (PD-1)–blocking antibody approved by FDA for the treatment of adult patients with mismatch repair deficient (dMMR) recurrent or advanced: 

• endometrial cancer, as determined by an FDA-approved test, that has progressed on or following prior treatment with a platinum-containing regimen, or

 • solid tumors, as determined by an FDA-approved test, that have progressed on or following prior treatment and who have no satisfactory alternative treatment options

FDA-approved tests for the detection of dMMR status is available at https://www.fda.gov/companiondiagnostics

Jemperli became the seventh immunotherapy cleared by the FDA that blocks signaling through either PD-1 or PD-L1 proteins, joining Merck & Co.’s Keytruda, Bristol Myers Squibb’s Opdivo and treatments from Roche, Pfizer, AstraZeneca and Regeneron.

It would be beneficial to identify small molecules that are affordable and easy to administer compared to expensive Jemperli, which costs $11000 for 500 mg or10 ml or make it affordable.

References:

1. Jemperli package insert (https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Jemperli/pdf/JEMPERLI-PI-MG.PDF)

2. Cercek A, Lumish M, Sinopoli J, Weiss J, Shia J, Lamendola-Essel M, El Dika IH, Segal N, Shcherba M, Sugarman R, Stadler Z, Yaeger R, Smith JJ, Rousseau B, Argiles G, Patel M, Desai A, Saltz LB, Widmar M, Iyer K, Zhang J, Gianino N, Crane C, Romesser PB, Pappou EP, Paty P, Garcia-Aguilar J, Gonen M, Gollub M, Weiser MR, Schalper KA, Diaz LA Jr. PD-1 Blockade in Mismatch Repair-Deficient, Locally Advanced Rectal Cancer. N Engl J Med. 2022 Jun 5. doi: 10.1056/NEJMoa2201445. Epub ahead of print. PMID: 35660797.

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