Chronic Lymphocytic Leukemia: Real World and QoL Evidence With BTKi

Transcript:

Sonali M. Smith, MD: What we’ve talked about so far has been data generated from prospective trials. But we’re all in clinic in the real world, so I’m going to ask Ryan to give us a review of what’s out there in terms of real-world evidence.

Ryan W. Jacobs, MD: Real-world data analysis can be helpful in a lot of situations. Patients treated outside trials don’t go through the same screening that we do in placing a patient on a trial. We don’t get the clinical trial nurse following that patient either. Outcomes can be different, and it’s nice to look at it in that way. Also, if you can find potential settings where you don’t have direct prospective comparisons, you can use real-world data to look into that. For example, we’ve been talking about ibrutinib vs acalabrutinib. If we don’t have a prospective trial in the first-line setting, there probably won’t be one done. It’s nice to look at real-world data in those circumstances.

What we saw at ASH [American Society of Hematology Annual Meeting] supports the data in terms of comparing toxicities seen in the ELEVATE-RR study. We see higher rates of A-Fib [atrial fibrillation] with ibrutinib. There are higher rates of hypertension and higher rates of bleeding. Despite the toxicity levels, questions come up. Is there a role for ibrutinib if we’ve got an agent that’s as effective but less toxic? In my clinic I’ve had patients who run into a toxicity issue with acalabrutinib. I was trying to think, in terms of FDA-approved options, can I try a patient on ibrutinib? We’d like to know, can we go from 1 BTK [Bruton tyrosine kinase] [inhibitor] to another and see success? There have been small numbers of prospective data looking at patients with ibrutinib and toxicity. Can they be treated with acalabrutinib? How does that look? Also at ASH, a poster looked at that in a real-world setting. It doesn’t work all the time. The real-world data at ASH showed about 40% of the time the acalabrutinib patients weren’t able to stay on acalabrutinib for a significant period of time. But a substantial number of patients can be converted from ibrutinib to acalabrutinib and stay on treatment.

Sonali M. Smith, MD: What we measure in trials or even collect in real-world evidence data sets are the patient perspectives. Susan, talk to us about health-related quality of life and some patient-reported outcomes [PROs].

Susan M. O’Brien, MD: To a large extent in CLL [chronic lymphocytic leukemia] and probably in cancer in general, PROs are relatively new. They’re probably not done as much as they should be. CLL lends itself to patient-reported outcomes for the following reason: we don’t treat asymptomatic patients. We watch and wait. By definition, patients who we’re starting on treatment are symptomatic. They’re in a perfect scenario, where you can potentially measure improvements easily in their symptoms. All the frontline BTK inhibitor trials have looked at PROs.

There are some similarities between the trials, but there are some differences. In RESONATE-2, ELEVATE-TN, and now in the SEQUOIA trial, there were PROs. The control arms are a little different, but they were all chemotherapy based. In RESONATE-2, it was single-agent chlorambucil. In ELEVATE-TN it was chlorambucil and obinutuzumab. In SEQUOIA it was bendamustine rituximab. But the 1 consistent finding and the 1 symptom that clearly improved much more significantly with all the BTK inhibitors than with a chemotherapy-based regimen was fatigue. Other symptoms also improved, but fatigue was consistent throughout all the trials. That’s an important symptom because if people are tired all the time, that impacts their quality of life. Fatigue was clear throughout all these trials, and there was a marked improvement compared with chemotherapy and immunotherapy with a BTK inhibitor.

Transcript edited for clarity.