Treatment Strategies for Patients With Double Refractory Chronic Lymphocytic Leukemia

At the 2023 Lymphoma, Leukemia & Myeloma Congress in New York, New York, Neil E. Kay, MD, Mayo Clinic in Rochester, Minnesota, shares expert insight into the pathobiology, treatment, and management of double refractory chronic lymphocytic leukemia (CLL), as well as how the leukemic cell plays a role in the disease becoming drug resistant. 

Transcript:

Hello, my name is Neil Kay. I'm a hematologist and I work at [the] Mayo Clinic in Rochester, Minnesota. I'm here today at the Leukemia, Lymphoma, [and] Myeloma meeting, and I was able to give a talk on the pathobiology and management of double refractory [chronic lymphocytic leukemia] (CLL). 

The talk consisted of 2 elements. The first is what might be the mechanisms that would generate double refractory CLL. And the last part of the talk was how would we treat patients as they evolve and ultimately become double refractory. To briefly summarize the first part of the talk, the discussion that I gave was mostly about how the leukemic cell itself plays a role in becoming drug-resistant and generating resistance mechanisms that ultimately lead to a patient being resistant, not just to the 1 major class of approved agents, but both, so that would be [Bruton's tyrosine kinase] (BTK) inhibitors as well as BCL2 inhibitors.

While this may take time because there are vigorous initial responses once the patient does get to this so-called double refractory status, the treatments and approaches are not well worked out yet. For most patients who are double refractory, treatment with clinically approved agents [is] short-lived. So clinical trials are probably the best way to treat your double refractory CLL patient if you have one.

If you don't have access to a clinical trial, then using a combination of agents, the BTK inhibitors and the BCL2 inhibitors, may re-sensitize patients so that ultimately you can get them to clinical trials. The last major comment I'd make is that we need to figure out how to better treat CLL patients initially as a required treatment so that less patients evolve into the double refractory state.

Source:

Kay N. Pathobiology and Management of Double Refractory CLL. Presented at Lymphoma, Leukemia & Myeloma Congress; October 18-21, 2023. New York, NY