Advancements in CLL: A Conversation With Dr Brian Koffman

For our coverage of the European Hematology Association (EHA) 2024 Congress, we spoke with Brian Koffman, MDCM, DCFP, FCFP, DABFP, MSEd, executive vice president and chief medical officer of the CLL Society. Himself a survivor of chronic lymphocytic leukemia (CLL), here he discusses recent treatment advancements in the CLL space, and the importance of addressing both unmet needs and patient treatment preferences. At EHA he chaired the session “Empowering Patient Journeys: A Collaborative Expedition Into Treatments and Emerging Frontiers in CLL.”

You can watch part 1 of his interview here.

Transcript

How have recent CLL therapeutic advancements impacted diagnosis and treatment considerations?

The rapidly evolving understanding of the biology of CLL has led to incredible advances in terms of how CLL is not only diagnosed, but how it's subdivided into different types and how those different types are treated. When I was diagnosed 19 years ago, there was much less understanding of the underlying biology; we just knew that some patients did worse. We understand much better why some patients do worse now. But more importantly, we have therapeutic options now that are agnostic to a lot of these poor prognostic factors that used to be so important in the era of chemoimmunotherapy. So patients with bad predictive markers are now doing extremely well with novel targeted therapies and new options that are constantly emerging.

How can providers effectively incorporate patient preferences into treatment?

When a clinician is making a decision about what treatment choice for their patient, there's many factors to consider. Obviously, the efficacy in terms of the overall survival, progression-free survival; obviously, the adverse event profile. But you've also got to look at that patient in front of you: What are their comorbidities? But even beyond that, what are their preferences? Are they a patient who is not going to be eager to be coming in, getting frequent lab work, getting IV [intravenous] infusions? Is an oral therapy going to be important to them? Are they going to want something that's limited duration that they can take for a short period of time, and then it's done? Are they very worried about adverse events or are they worried about immunosuppression?

These different types of approaches that patients have in terms of what's most important to them, part of our mission as clinicians is to find out what's most important to my patient, what's their major part in this so you can make a shared decision about what the next step forward should be for that patient.

What are current unmet needs in this space, and what strategies can be used to address these needs?

In terms of what the unmet needs are for CLL patients, let me take you from the journey. I think in the US, the diagnosis is pretty clear, but sadly, not all patients are getting appropriate prognostic and predictive testing. And even though the new therapies are mostly agnostic to this, it's still important in terms of determining the therapies to know what's going on. These things completely evolve over time, often usually in a negative direction. So it's important to retest—at the CLL Society, we have a motto “Test Before Treat”—and after each line of therapy, patients need to be reassessed to see if any new subclones have emerged. This is not happening.

Patients are not always being offered access to the newest and latest therapies. Too many patients are still getting chemoimmunotherapy when it often is inappropriate for them. When patients are diagnosed with CLL, told that it's an incurable cancer, and then told we're not going to do anything about this, this is a tremendous stress on these patients. And they need some support. It may not be that they need to see a psychologist or a social worker, but maybe they need to talk to another patient, maybe they need a support group. This is a tremendous unmet need that is underrecognized.

In terms as they move along in the therapeutic journey, while we have excellent frontline and second-line therapies, when patients become double refractory—they failed a BCL-2 inhibitor, they failed the B-cell receptor pathway blockers, BTKis [Bruton tyrosine kinase inhibitors], they’re really out of strong options at this point. And while we now have an approved CAR T [chimeric antigen receptor T-cell] therapy, and we have a noncovalent BTK agent that's available, we need more therapies. We don't have a cure for most patients, we don't have a functional cure, so CLL is not a solved problem. We're very thankful as patients that we're living longer, but we're needing more therapies to extend that even longer.

Two other major unmet needs that I need to mention: CLL is a cancer of the immune system. Too many of us are still dying of infectious complications, both of the CLL itself and in its treatment and of second malignancies. CLL patients are prone to a whole host of second malignancies, skin cancer being the most prevalent. So the compromised immune system is a big issue for the CLL patients. The other big issue is Richter transformation, and a small but significant percentage of CLL patients go on to transform usually to diffuse large B-cell lymphoma, and that prognosis is dismal, usually measured in months for patients, and we have no good therapies there. So that's a screaming unmet need for CLL patients.