I went to the Advances in Cancer Immunotherapy talk. It was a big talk, covered lots of topics, started with bispecific T-cell engagers with kind of a refresher on the mechanism of action and the review of side effects, which includes cytokine release syndrome and ICANS grading and management. A clinical pearl to take away from it–that the time to onset varies between drugs from a few hours to up to 48 hours after administration of drug. Management varies as well between the liquid tumors and the solid tumors.
With grade 2 cytokine release syndrome, you can consider toci and steroids, as opposed to it being given with some of the multiple myeloma drugs. Many regimens also are being given as inpatient for the first dose or two, as we try to find a way to manage cytokine release syndrome outpatient, though some are being given outpatient as well.
They then moved on to talk about immunotherapy toxicities. Renal and hepatic toxicities were covered, and onto even triple M syndrome. The incidence of renal toxicities was anywhere from 20% to 50%. It oftentimes presents with other immunotherapy-related adverse events first, so it presents as dehydration, kind of vague symptoms. And then you can give steroids and taper down and re-challenge if they just started having the toxicity or if a patient recovers quickly with steroids in less than a week. I thought that was really interesting. Oftentimes we’re holding patients for longer.
For hepatic adverse events, they’re more rare–5–8% of patients get them and typically within 3 months of onset. I believe it was 70%. Twelve percent of hepatic IO toxicities are actually steroid refractory. For grade 3, you're going to give IV steroids over oral steroids.
And then grade 2 toxicities–for hepatic toxicities and above, you'll consult the specialist.
Interestingly, for triple M syndrome–which we don’t see a lot but it's very important to know about because it can be so deadly–it's made up of myocarditis, myasthenia gravis, and myositis.
I never think about myasthenia gravis, probably because it occurs in less than 1%, but it's part of triple M syndrome. It’s also very difficult to diagnose as it presents similarly to myositis. The onset can be 4–6 weeks, fatality can be up to 75%. And interestingly, ocular toxicity is related to poor prognosis.
As well as myocarditis–there's a lot of information on myocarditis–up to 50% fatality with myocarditis, median onset of 30 days and most often within 3 weeks from drug. And then prior cardiac history is a risk factor. This was a very interesting talk with a lot of things that we don't often see in very rare toxicities.
I reviewed the poster on the RUBY trial, which was a phase 3 trial comparing dostarlimab and carboplatin-paclitaxel to a placebo and chemotherapy in primary, advanced, and recurrent endometrial cancer. They looked at time to subsequent therapy and overall it showed prolonged and sustained benefits to the patients that received dostarlimab and carboplatin-paclitaxel, with median time to next therapy not even reached, especially in the MSI high population.
I also got to see the poster on the Stanford Early Drug Development Team utilizing the APPs in their clinical trial group with a pilot program doing an early drug development consult program for patients on clinical trials who were admitted to the hospital unexpectedly. They did their consults by phone, and they looked at about 6 months' worth of the consults. The program showed streamlined communication, creating a clear pathway for discussion of inpatient issues for patients on clinical trials and ensured protocol adherence and toxicity management, as well as improved source documentation. Future studies will look at the length of stay and readmission rates and the impact of this program on those subjects.
