According to CLL Pharmacist, results from the Phase 3 GENUINE trial show that, when taken in conjunction, ibrutinib and ublituximab lead to better patient outcomes than either drug alone. The GENUINE trial was designed to test the drugs’ efficacy and safety in patients with high-risk chronic lymphocytic leukemia (CLL).
GENUINE Trial
In June, the ASCO held their virtual annual meeting. During this time, researchers shared results from the GENUINE trial. Median patient follow-up was performed for 3.5 years. The trial sought to understand whether ibrutinib and ublituximab, when taken together, were more effective than either drug alone. Although ibrutinib has been previously seen to improve patient outcomes, it experienced problems in durability and disease control.
Ublituximab, the other drug being tested, is a glycoengineered monoclonal antibody. But what does that mean? According to the American Cancer Society, monoclonal antibodies (mAB):
are man-made proteins that act like human antibodies in the immune system. Researchers can design antibodies that specifically target a certain antigen, such as one found on cancer cells.
So ublituximab is designed to specifically target cancerous cells with a certain type of antigen.
Study Specifics
Within the GENUINE trial, there were 117 participants with a median age of 66 years old. To be eligible to participate, patients required:
- Relapsed or refractory CLL
- A doctor-confirmed deletion 17p, 11q, or TP53 mutation
- 1-5 prior treatments (not including ibrutinib)
Out of all participants, 58 received ibrutinib and 59 received the ibrutinib-ublituximab combination. In both cases, patients received 420mg ibrutinib daily. For those receiving a combination, 900mg ublituximab was administered on the 1st, 8th, and 15th day (during the first cycle). For subsequent cycles, patients received this dose only on the first day.
During the course of the trial, researchers were seeking two endpoints:
- Primary: overall response rate
- Secondary: complete response rate, survival without disease progression, safety
Most patients had more aggressive cases of CLL and were unlikely to respond to other forms of treatment, such as chemoimmunotherapy. Additionally, more patients with deletion 17p received ibrutinib without ublituximab.
Findings: Drug Combination Therapy for CLL
Ultimately, the GENUINE trial found the following:
- 53% of patients in the combination therapy arm experienced adverse reactions related to ublituximab infusion. However, only 3% of reactions were severe.
- Patients in the combination therapy arm experienced 17% more neutropenia instances than those taking just ibrutinib.
- Those taking both ibrutinib and ublituximab experienced more progression-free survival than those taking just one drug. This is especially true in patients with deletion 17p or mutation TP53, marking the combination as a potentially effective and significant treatment option.
- The overall survival rate for patients within the combination therapy arm was 82% after 4 years. For those taking just ibrutinib, the overall survival rate was 70%.
Chronic Lymphocytic Leukemia (CLL)
Though doctors are not sure of the exact cause of chronic lymphocytic leukemia (CLL), this rare cancer of the blood and bone marrow occurs during mutations of blood-producing cells. Once mutated, blood cells produce ineffective lymphocytes, a type of white blood cell. When healthy, lymphocytes play a role in immune response and fighting infections. However, in patients with CLL, their abnormal cells crowd out healthy cells, causing health issues. Overall, CLL is the 2nd most common form of leukemia in adult patients.
Though many patients may not show symptoms, particularly in early stages, those that appear may include:
- Fever
- Fatigue
- Swollen, but painless, lymph nodes
- Frequent infections
- Unintended weight loss
- Easy bruising
- Abdominal pain
- Spleen enlargement
Learn more about CLL here.
