Introduction and CLL Background

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EP: 1.Introduction and CLL Background

EP: 2.ELEVATE-RR Study Overview

EP: 3.Patient Characteristics in ELEVATE-RR

EP: 4.ELEVATE-RR: Efficacy Data

EP: 5.ELEVATE-RR: Safety Data

EP: 6.Key Takeaways and Clinical Implications

EP: 7.Unmet Needs and Future Directions in CLL

EP: 8.Recap: Noninferiority Comparison of Acalabrutinib and Ibrutinib for Previously Treated CLL

Michael R. Bishop, MD: Welcome to CancerNetwork® Between The Lines journal club. I’m Dr Michael Bishop. I’m the director of the David and Etta Jonas Center for Cellular Therapy at the University of Chicago and a member of the lymphoma program at the University of Chicago. I’m joined by a good friend and colleague, Dr Bruce Bank, who’s from Northwest Oncology & Hematology in Rolling Meadows, Illinois. Dr Bank and I collaborate in the care of a number of patients with hematologic malignancies. He was kind enough to agree to join us for this journal club experience.

The article that we’re going to be reviewing tonight is titled, “Acalabrutinib Versus Ibrutinib in Previously Treated Chronic Lymphocytic Leukemia: Results of the First Randomized Phase III Trial.” This article was published in the Journal of Clinical Oncology in July of 2021. The first author is John Byrd, [MD]. If you’re interested in pulling this article up during the recording and following along, we’d love for you to do so. You can see that the reference is at the bottom right corner. This was in volume 39 on page 3441. You can pull that up if you’re an ASCO [American Society of Clinical Oncology] member or pull it up online, get it from PubMed, or anything that you’d like to do.

As a prelude to all this, Bruce has a focus on hematologic malignancies, which is why I enjoy working with him. Bruce, can you tell me a little about the typical patient with CLL [chronic lymphocytic leukemia] you see in your practice?

Bruce B. Bank, MD: First of all, thanks very much for inviting me to participate in this. I look forward to learning a lot from you, as I usually do when I work with you and collaborate on patient care. We’ve typically been seeing more patients who have basically normal CBC [complete blood count] results except for a slightly elevated WBC [white blood cell count], maybe in the range of 15 to 20 per μL, and an automated differential that shows a slight preponderance of lymphocytes. This is how most of our patients are presenting, at least to my clinic, for a new consultation these days.

Michael R. Bishop, MD: Bruce, let me follow up on that. I gave a lecture last night and one of the questions to me was, what are the indications to start therapy for a patient with chronic lymphocytic leukemia? Or small lymphocytic lymphoma, whichever you want to refer to. I thought that was a great question. I’d love to hear your answer to that.

Bruce B. Bank, MD: I’ve always found this to be a very vexing question because I find that there are some patients who you know have to start therapy, there are patients who definitely don’t need therapy, and there are quite a few patients in the gray area. Clearly, patients who are having signs of hemolytic anemia, significant autoimmune cytopenias, or bone marrow failure require treatment. Patients who have symptomatic lymphadenopathy or abdominal organomegaly require treatment.

There are patients who are in a gray area. For example, one thing that I usually find to be vexing is when a patient feels well and has a sky-high white blood cell count. It drives everybody crazy. The patient tends to get frustrated. Everybody knows arithmetic, so a patient who’s looking at himself having a white blood cell count of 150 or 200 per μL is starting to get antsy about it. Certainly, the referring physicians are. I always find it difficult to know whether those patients should be treated right away. I tend to not just because I’m not persuaded that the patients have a better outcome if we treat them early. But [we] certainly [treat] patients who become symptomatically anemic or have discomfort from their lymphadenopathy.

One other symptom that has come into the foreground for me is generalized fatigue. There are data to back up that some patients develop fatigue even without a lot of lymphadenopathy or a lot of cytopenias. It’s always difficult to figure that out because these are usually older patients who have half a dozen other possible reasons for being fatigued. But if I don’t find any other good reason, that’s a possible reason to initiate treatment.

Michael R. Bishop, MD: I share all of those thoughts and criteria for my patient population too. I see more refractory chronic lymphocytic leukemia, knowing that this is probably one of the more common hematologic malignancies you’re going to see in your practice. Those are all very relevant. When you treat, what’s your go-to therapy? Does it depend on the patient? What’s the role of Bruton tyrosine kinase [BTK] inhibitors in your clinical practice?

Bruce B. Bank, MD: We distinguish a little based on the patients. With patients who have extremely aggressive disease, by which I mean extremely symptomatic, profound cytopenias, or lymphadenopathy all over the place, if we do a PET [positron emission tomography] scan on these patients and they have a fair amount of PET avidity in their lymph nodes, I sometimes recommend an aggressive regimen like R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone]. Fortunately, that isn’t for too many patients, but there are patients like that. For the more common presentation of a patient who requires treatment, BTK inhibitors [BTKIs] are the best way to start. It hasn’t been that long since ibrutinib hit our radars and looked great. In our group, we had 4 patients on the E1912 study. I don’t remember whether that’s one of the ELEVATE studies.

Michael R. Bishop, MD: That’s one of the early trials. That’s right.

Bruce B. Bank, MD: Luckily in our practice, 3 of those 4 patients got randomized to the ibrutinib-rituximab arm, and they’ve all done well. In fact, 2 of them are in a sustained CR [complete response]. I’ve been lucky because neither of them have had any major toxicity from it. Off study—this must be my magic touch or something—the published risk of cardiac events, especially atrial fibrillation, with ibrutinib is around 20% or 25%. In my case, it’s around 80%. The older they are, the more likely it is, which is probably consistent with the published data. At least in 1 case, it wasn’t reversible. A couple of cases were quite symptomatic. I’ve found that to be a deal-breaker. You can work around the other stuff, like minor bleeding, but I’ve found the cardiac stuff vexing.

Michael R. Bishop, MD: What’s your go-to BTKI?

Bruce B. Bank, MD: Right now, it’s acalabrutinib. I’m not just saying that.

Michael R. Bishop, MD: You’ve set this up well. Bruce and I deliberately hadn’t talked about this other than saying, “Here’s the article.” He and I enjoy a lively discussion. He set that up beautifully.

Transcript edited for clarity.