Relapsed Or Refractory Chronic Lymphocytic Leukemia: Treatment Options
For patients with relapsed or refractory CLL after chemoimmunotherapy the treatment options are Imbruvica (ibrutinib) monotherapy or Venclexta (venetoclax) combined with Rituxan (rituximab).
Imbruvica is an oral kinase inhibitor treatment that is continued until it is no longer effective or if the patient develops intolerable toxicity. Imbruvica is a small molecule drug that binds permanently the protein Bruton’s tyrosine kinase inhibiting its function, which is critical for B cell proliferation. The most common side effects of Imbruvica are low platelet count, diarrhea, low white blood cell count, anemia, fatigue, muscular pain spasm, and joint pain. In relapsed patients the time to progression with Imbruvica was approximately 51 months. In general Imbruvica, is well tolerated even in older patients.
Another combination therapy that can be used in refractory CLL is venclexta plus Rituxan. Venclexta is an oral drug that binds to BDL-2. BCL-2 when you have CLL builds us preventing cancer cells from self-destructing. Venclexta binds to BCL-2 restoring the process of self-destruction. Rituximab is a monoclonal antibody that binds to CD20 antigen which is a protein overexpressed on CLL cells.
Rituximab is given intravenously over several hours. With the combination of venclexta and rituximab 92% of patients had some level of response. The most common side effects of the combination therapy are low white cell count, diarrhea, cough, pneumonia, fatigue and nausea.
The most serious side effect from Rituxan and Venclexta combination is tumor lysis syndrome, which can be life threatening and the patient needs to be monitored closely and preventive measure needs to be taken. Additional novel agents continue to be studied and some are currently in phase III trials and could change the current standard of care.