During a recent PW podcast episode, Gita Thanarajasingam, MD, a hematologist and researcher at Mayo Clinic, talked about the assessment and reporting of adverse events in treatments for chronic myeloid leukemia (CML). The following includes highlights from that interview.
I’ve realized that we did a poor job understanding how patients with CML feel and function on treatment. We put a lot of emphasis into improving cure rates and novel therapeutics.
The tyrosine kinase inhibitors, which had miraculous response rates, were some of the first noncytotoxic chemotherapies to have a profound impact, allowing people to live with their disease as a chronic condition. We’ve always looked at side effects as if they’re not severe when they don’t require hospitalization or aren’t life-threatening. we’ll tolerate them because we want the efficacy.
But when you think about oral treatments that are chronically administered, or some of the newer immune therapies, cellular therapies like CAR T, you have to consider toxicity differently.
How our patients feel and function over time on treatment matters a lot more than it used to when we were focused on just wanting patients with cancer to live. We have improved outcomes and better progression-free and overall survival rates for many different cancers, but we haven’t really modernized our approach when looking at side effects or the patient experience during treatment.
When we talk about toxicity or side effects of cancer treatment, there’s a grading system that we use called the CTCAE. Usually, a grade 3 or 4 event is something that’s life threatening. Grade 5 is a side effect that causes death. But if you are a patient receiving therapy for CML and you’ve been taking imatinib for years at a time, you may have an effect that limits your ability to live your life or impacts your QOL.
For example, grade 2 diarrhea is a bowel movement four to six higher than a person’s baseline. So, if someone normally produced two stools a day, but were now producing up to eight stools a day, that would be considered a grade 2 event. But that’s usually not reported. Clinicians are trained to consider this as “low grade,” thinking it’s acceptable if patients are tolerating it well. But I challenge you to think of anybody who can function in their life, or in their work, with this type of intrusive side effect.
We sometimes use tolerability as an interchangeable concept, when something can be safe but it’s completely intolerable. To understand this concept of tolerability, you have to involve the patient’s perspective, because what may be tolerable to you may be completely intolerable to me.