Monday, May 22, 2017

Neurologic side effects to immunotherapy with treatment algorithm

I have been posting individual articles as well as collections of abstracts regarding possible side effect of immunotherapy for years.  I figure...forewarned is forearmed.  Here is the latest post with a link to prior:  The mice told us so...cardiotoxicity - with links to more articles related to the possible side effects of immunotherapy

Additionally, I've reported on what the experts tell us in regard to dealing with these side effects:
Here in a discussion:  Side effects and how to manage them - Weber and Agarwala

And this report that includes multiple charts with algorithms for treatments of GI, endocrine, pulmonary and hepatic side effects:  How to deal with side effects from anti-PD-1

Now there's this:

Neurologic Serious Adverse Events Associated with Nivolumab Plus Ipilimumab or Nivolumab Alone in Advanced Melanoma, Including a Case Series of Encephalitis.  Larkin, Chmielowski ... Hodi ...Weber, et al. The Oncologist. May 11, 2017.  

Despite unprecedented efficacy across multiple tumor types, immune checkpoint inhibitor therapy is associated with a unique and wide spectrum of immune-related adverse events (irAEs), including neurologic events ranging from mild headache to potentially life-threatening encephalitis. Here, we summarize neurologic irAEs associated with nivolumab and ipilimumab melanoma treatment, present cases of treatment related encephalitis, and provide practical guidance on diagnosis and management. Methods. We searched a Global Pharmaco-vigilance and Epidemiology database for neurologic irAEs reported over an 8- year period in patients with advanced melanoma receiving nivolumab with or without ipilimumab from 12 studies sponsored by Bristol-Myers Squibb. Serious neurologic irAEs were reviewed, and relationship to nivolumab or ipilimumab was assigned. Results. In our search of 3,763 patients, 35 patients (0.93%) presented with 43 serious neurologic irAEs, including neuropathy (n 5 22), noninfective meningitis (n 5 5), encephalitis (n 5 6), neuromuscular disorders (n 5 3), and nonspecific adverse events (n 5 7). Study drug was discontinued (n 5 20), interrupted (n 5 8), or unchanged (n 5 7). Most neurologic irAEs resolved (26/35 patients; 75%). Overall, median time to onset was 45 days (range 1–170) and to resolution was 32 days (2–8091). Median time to onset of encephalitis was 55.5 days (range 18–297); four cases resolved and one was fatal. Conclusion. Both oncologists and neurologists need to be aware of signs and symptoms of serious but uncommon neurologic irAEs associated with checkpoint inhibitors. Prompt diagnosis and management using an established algorithm are critical to minimize serious complications from these neurologic irAEs.

[with this algorithm]

I hope this is information you will never need....but if you do....I hope it helps. - c


  1. Thanks for posting The Trametinib dose reduction should be 2mg 1.5 mg .5 mg Ithink

  2. Thanks, Mike. Sharp eyes! Your comment should be on the BRAF/MEK post following this one...but I think you have spotted an important typo in that chart and I will make a note of it!!!