Patients with CLL whose cancer cells have become unresponsive to targeted therapies like venetoclax or BTK inhibitors need treatment options. Immunotherapies that strengthen the patient’s own cancer-killing immune system cells like CAR T-cell therapy have shown promising results in treating this patient group. Although CAR T-cell therapy is FDA-approved for a few other blood cancers, it is still in clinical trials for CLL. To join clinical trials to receive CAR T-cell therapy, see here (in the search by keyword bar place CAR T). 

Personalizing CLL Treatment with Current Therapies 

Until CAR T-cell therapy gets approved for CLL, researchers are continuing to evaluate other treatment options for this relapsed/refractory patient group. One of the things being reviewed is completing a medicine sensitivity screening using a sample of the patient’s blood and evaluating how the sample reacts with multiple different types of medicines approved for blood cancers in a lab. When researchers find the most effective one, they then give that treatment to the patient. 

The researchers found success with this method. Each patient’s CLL cells may respond differently to types of medicines. Personalizing therapy can help find the most effective treatment for patients early on.

More about the study 

The study that proved this was conducted in Norway helping a 70-year-old CLL patient. He had several chemo-associated high-risk genetic features such as unmutated IGHV, mutated TP53, and deletion of chromosome 13q14. He had previously been treated with and become unresponsive to ibrutinib and idelalisib, alemtuzumab (treatment worked for a period of time but then the CLL came back), venetoclax/rituximab (he achieved a full reduction of CLL signs/symptoms with no CLL cells present in the blood using highly sensitive tests [undetectable minimal residual disease uMRD] but after 2.5 years post treatment, the CLL came back and he had severe bone marrow failure. He was then retreated with venetoclax which did not work. 

Researchers found that after the remission that followed the first venetoclax/rituximab treatment, the patient’s cancer-killing immune system T-cells and natural killer (NK) cells increased on their own and were doing a good job at reducing any new CLL cells that came up but the T-cells and NK cells became exhausted which then allowed the CLL cells to grow again. One reason cancer-killing immune system cells may become exhausted is from excess oxidative stress (see here for more about excess oxidative stress). 

At this point, the researchers took samples of the patient’s blood and ran tests in the lab comparing his blood sample to other treatment options to find what would be effective for him. The medicine they found that helped reduce the patient’s CLL cells in the lab was ixazomib citrate (a proteasome inhibitor currently approved for the treatment of another type of blood cancer called multiple myeloma). 

After seeing the success of the treatment in the lab on the patient’s blood sample, they gave the patient this treatment to take internally for seven weeks and evaluated how he was doing each week. After the treatment period, the patient’s blood cells of reticulocytes, thrombocytes, and hemoglobin numbers increased. He no longer needed transfusions and no longer had bleeding issues. He was able to exercise again and now has an active life. 

Using medicine sensitivity screens to personalize treatment options for CLL patients can help avoid ineffective therapies. The screening test can be conducted and analyzed in 5 days. Talk to your CLL specialist about medicine sensitivity screening before starting treatment to help your treatment go the best it can.