NorthWest Biotherapeutics Inc (NWBO)

[CogDiss 1188X]

Longfellow — thought you might find this of interest. A large review of adverse effects in 125 ICI clinical trials involving 20,128 patients. The abstract doesn’t break out grade 4 or 5 AEs (refers to > grade 3) and doesn’t look at hyper progression. Go figure.

Results: This systematic review and meta-analysis included 125 clinical trials involving 20?128 patients; 12 277 (66.0%) of 18?610 patients from 106 studies developed at least 1 adverse event of any grade (severity), and 2627 (14.0%) of 18 715 patients from 110 studies developed at least 1 adverse event of grade 3 or higher severity. The most common all-grade adverse events were fatigue (18.26%; 95% CI, 16.49%-20.11%), pruritus (10.61%; 95% CI, 9.46%-11.83%), and diarrhea (9.47%; 95% CI, 8.43%-10.58%). The most common grade 3 or higher adverse events were fatigue (0.89%; 95% CI, 0.69%-1.14%), anemia (0.78%; 95% CI, 0.59%-1.02%), and aspartate aminotransferase increase (0.75%; 95% CI, 0.56%-0.99%). Hypothyroidism (6.07%; 95% CI, 5.35%-6.85%) and hyperthyroidism (2.82%; 95% CI, 2.40%-3.29%) were the most frequent all-grade endocrine immune-related adverse events. Nivolumab was associated with higher mean incidences of all-grade adverse events compared with pembrolizumab (odds ratio [OR], 1.28; 95% CI, 0.97-1.79) and grade 3 or higher adverse events (OR, 1.30; 95% CI, 0.89-2.00). PD-1 inhibitors were associated with a higher mean incidence of grade 3 or higher adverse events compared with PD-L1 inhibitors (OR, 1.58; 95% CI, 1.00-2.54).

https://jamanetwork.com/journals/jamaoncology/article-abstract/2731143

Grade 3 definition:
Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care (eg, can’t bathe or use toilet on own)

Grade 4 def:
Life-threatening consequences; urgent intervention indicated.

Grade 5 def:
Death related to AE

https://www.eortc.be/services/doc/ctc/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf