‘Promising Times’ for Patients With CLL

A fixed-duration treatment regimen of Imbruvica (ibrutinib) and Venclexta (venetoclax) may lead to better progression-free survival, as well as less time spent in the hospital, for patients with chronic lymphocytic leukemia (CLL).

Results from this study were presented at the European Hematology Association 2021 Virtual Congress.

“These are promising times for patients with CLL. Unfortunately, we still (can’t) say that we have cured the disease, but, for sure, we have prolonged progression-free survival,” lead study author Dr. Arnon P. Kater, a professor at Amsterdam University Medical Centers, locatie AMC, in the Netherlands, told CURE®. “These new agents also improved quality of life, not only when (a) patient is in remission, but specifically also when a patient is under treatment.”

Of note, the standard of care is indefinite treatment with anti-CD20 therapy in combination with chemotherapy or Venclexta, or Imbruvica alone.

In the study, the combined treatment of Imbruvica and Venclexta, compared with the standard of care of Leukeran (chlorambucil) and Gazyva (obinutuzumab), reduced the risk of disease progression or death by 78% after a median follow-up of 28 months. The treatment regimen was 12 weeks.

The drug combination works well because the cancer cell behavior of CLL in the lymph nodes creates a microenvironmental protective niche, Kater said. This niche uses protective signals from other cells in the body and allows the cancerous cells to proliferate rapidly. Imbruvica inhibits this, prevents new cells from migrating to the lymph nodes and causes them to exit the lymph nodes. Venclexta, on the other hand, is an inhibitor of the protein BCL-2, which is known to be increased in patients with CLL and is responsible for the survival of cancerous cells in the blood. The cancerous cells die when this protein is inhibited.

“That’s why, theoretically, there might be very much of a synergy between the two drugs because one drug is very good (at) killing cells in the blood (Venclexta), and the other drug is very good in getting the cells out of these protective niches in the lymph nodes and maybe other organs as well,” Kater said.

After reviewing the data, Dr. Akiva Diamond, an assistant professor of medicine in hematology and oncology at Baylor College of Medicine in Houston, wondered what oncologists would be able to do next if the combination did not work for the patient. “These are our two best drugs, and we’re starting with them together. What do we do next?” he said. “That’s going to be a very important question for us as investigators and for patients. Are we able to reuse this again later? If, let’s say, they get a good few years of benefit, can we try it again? ... Or is there going to be a resistance to these two agents and then we need to move to the next line of therapy? So there (are) still a lot of questions to be answered, but certainly (the treatment has) promising efficacy.”

Outside of the projected efficacy of the two drugs, other benefits include that the regimen is fixed duration and that it is administered mainly in an outpatient setting. “I think that a fixed-rate treatment is the preferred option (for three reasons),” Kater said. These reasons include the fact that patients have a shorter time frame for experiencing side effects, the possibility of reducing financial burden by shortening the duration of treatments and the increased possibility of using the same agents for years versus treating a patient until cells become resistant.

Diamond also emphasized the importance of outpatient treatment options such as this combination compared with others like Leukeran and Gazyva, as well as Venclexta and Gazyva. “Currently, (taking Venclexta and Gazyva) ... does require quite a bit of hospitalization. So during the (COVID-19) era, we’ve been using a lot less of it and using that less frequently because patients (are) really looking to avoid hospitalizations,” he explained. “I’m hopeful that with this therapy, we might have the option to first start with (Imbruvica), decrease the disease burden and then be able to do the rest of the treatment maybe as an out- patient. I think that would be a benefit.”

Kater added that there is the possibility of differentiating data due to regional differences for older and frail patients from the study. Of note, there were no new side effects outside of those already common to the drugs when used as single agents. Common side effects of Venclexta and Imbruvica include arrythmia (irregular heart rhythm) and hypertension. “I think it’s a very promising combination,” Kater explained. “But I think this is really something that both the doctor and the patient should be aware of.”

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