Relapsed/Refractory CLL Treatment Options

On June 25th, as part of HealthTree’s CLL Webinar Program, CLL specialist Kerry Rogers, M.D., from OSUCCC-James shared insight about the treatment options available to CLL patients whose disease was not responsive to venetoclax and covalent BTK inhibitors. Watch the event's recording below or read the summary. 

What is Relapsed/Refractory CLL? 

Relapse refers to CLL returning after the patient finishes treatment and experiences a period of remission over six months. Remission means the disease signs and symptoms were either partially or fully reduced. CLL patients usually experience up to several years of remission after taking the fixed-duration treatment combination of venetoclax (Venclexta, AbbVie) and obinutuzumab (Gazyva, Genentech). 

Refractory means that CLL became resistant to treatment or came back within six months after finishing therapy. Refractory CLL is observed in patients who take covalent BTK inhibitors continuously over several years, such as ibrutinib (Imbruvica, Janssen Biotech), acalabrutinib (Calquence, AstraZeneca), and zanubrutinib (Brukinsa, BeiGene). CLL patients may also become refractory to venetoclax. 

As of 2024, CLL is not considered to be curable. Relapsed and refractory CLL are the expected evolution of the disease. CLL needs long-term management with multiple lines of therapy during a patient’s life. 

CLL Treatment Options After Venetoclax and Covalent BTK Inhibitors

If CLL patients cannot take venetoclax or covalent BTK inhibitors either from intolerance to side effects or because CLL cells have become refractory to the medicines, other treatment options are needed to continue limiting the progression of the disease. Dr. Rogers mentioned several new medicines for this patient group. These include: 

• FDA-approved relapsed/refractory CLL treatment options 
  • Pirtobrutinib (Jaypirca, Eli Lilly): A non-covalent BTK inhibitor that binds to the CLL cells in a different way than covalent BTK inhibitors, allowing the medicine to inhibit CLL progression despite prior resistance to covalent BTK inhibitors. 
  • Liso-cel (Breyanzi, BMS): A CAR T-cell therapy that works by re-engineering a patient’s T-cells to more effectively kill CLL cells. 
  • Allogeneic stem cell transplant: The patient receives an infusion of donor stem cells (cells capable of forming all other types of blood cells). Because of its side effects, this treatment is often considered a last resort for CLL patients. 
• Relapsed/refractory CLL treatment options in clinical trials 
  • BTK degraders: They target and remove the BTK protein on CLL cells, allowing for treatment effectiveness despite prior BTK inhibitor intolerance. 
  • Sonrotoclax (BeiGene): A second-generation BCL-2 inhibitor. 
  • Bispecific antibodies: Immunotherapy that brings cancer-killing T-cells near CLL cells to kill them. 

Audience Q&A 

During the event, Dr. Rogers answered several patient questions. Some of these included: 

• [Timestamp 46:25] If I’ve previously been treated with venetoclax and ibrutinib, should I consider a clinical trial first or choose a treatment that is already FDA-approved, like CAR T-cell therapy or pirtobrutininb? 
• [Timestamp 51:50] Are patients pre-educated about side effect management strategies before they receive treatment to help reduce fear? 
• [Timestamp 55:42] How do you manage the side effects seen with pirtobrutinib? 

To listen to these questions’ answers in the event’s recording, please click the timestamp links. 

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