Ibrutinib Improves Outcomes Over Rituximab Among Patients With Advanced CLL/SLL

Shenmiao Yang, MD, Peking University Institute of Hematology, Peking University People’s Hospital, Peking, China, discusses a phase 3 trial of ibrutinib versus rituximab in patients with advanced chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL). Ibrutinib was found to have a lower risk of Hepatitis B virus (HBV) reactivation when compared with rituximab in these patients.

Transcript
My name is Shenmiao Yang. I'm working at the Peking University Institute of Hematology. My interest is CLL and other lymphomas.

The incidence of CLL in China is really very low, but the institute is almost the biggest one in China. I have a lot of CLL patients. The population of China is really very big. No matter the incidence is low, I have a lot of such kinds of patients. Just like today, I saw more than 20 CLL patients in my outpatient clinic.

I participated in the study of C3002 in 2014. At that time, ibrutinib had already been approved in the United States. Janssen came to China and asked if my boss, the PI of that study, Professor Xiaojun Huang, wanted to participate in an Asia Pacific study. They launched the study in China and my boss said, "Yes." I was the sub PI of that study.

The study tried to compare ibrutinib with rituximab. Obviously, rituximab is not a good option for CLL patients, but at that time, the RESONATE study just compared ibrutinib with ofatumumab in Western countries.

In China, we do not have ofatumumab. At that time, we did not have obinutuzumab either. The only control we can trust is rituximab.

The study was designed as a comparison of ibrutinib with rituximab single agents in refractory and relapsed (R/R) CLL patients. The result, I think, is excellent.

At that time, I had a lot of patients, and we did not have any method to letting them get better. But with the study drug, ibrutinib, the patients got the response very fast, and really came back to us, I think, because many of them would die very soon.

Later, we completed that study, and then ibrutinib was launched in China. As you know, we now have many choices of BTK inhibitors in China. Not only ibrutinib, but also zanubrutinib and orelabrutinib, have already been approved by the Chinese FDA. My patients really have a lot of options.

In China, there are some local characteristics or features of the CLL patients. As everybody knows, the incidence is very low and many CLL experts have some idea about Asian CLL.

In 2019, the Edinburgh in the iwCLL meeting, at that time, I gave a presentation on CLL in China. After my talk, many professors, they came to me. A lot of very famous professors at that time. I was so excited to talk with them. Many of them came to me and said they believed Asian CLL patients are totally different from the Western CLL patients. They consider the Asians will have more sick patients and will be worse responding to all the treatment.

Besides that characteristic, we also have a problem of HBV infection. In China, in 2000, the Sun Yat-sen Cancer Center, they published some study and summarize the (HBV infection among) B-cell lymphoma patients.

I think the data is about 30% of the patients have HBV antigen positivity. So it's really a very big proportion of the patients. In the study of ibrutinib—actually the study does not command all the investigators to give the prophylaxis of the HBV reactivation.

At the time, I really did not get any of the information about HBV reactivation from the previous studies. I think it's OK if the patients did not have HBV antigen positivity, and they did not have the HBV-DNA positivity, they could be safe in the treatment.

After that study also, we have zanubrutinib and orelabrutinib studies. To my surprise, companies just almost copy the protocols of ibrutinib. Also, they do not have the prophylaxis command of HBV reactivation. But there are some patients really got the reactivation and also someone get very sick.

We were so surprised at that time because we have already completed the ibrutinib study—almost for 1 year, but now we just had to consider the differences between various BTK inhibitors. They can work. They are doing almost the same, but the reactivation rate seems higher in the next-generation BTK inhibitors.

At the time, we made the modification to the protocols, and gave prophylaxis of HBV reactivation drugs to all the patients with the resolved HBV infection, which means they have HBc antibody positivity without the surface antigen positivity. That's the beginning of the story.

After all that experience, we have already come to the post-hoc study. I just asked the statisticians to review the data. I really have the feeling that we did not have so much (HBV) reactivation in the ibrutinib study. My feeling is right. After the statistician gave me the report, I found it is quite safe in the ibrutinib study.

It's very interesting because the next-generation BTK inhibitors (are reported to) have a much safer profile. They have very low incidence of atrial fibrillation. It is believed they have more that the intensive potential to control the disease.

According to the result of the post-hoc study, I just consider maybe there is some difference between the antivirus potential (of different BTK inhibitors).

I don't know if the ibrutinib helps T cells to prevent the reactivation of HBV. I don't know, but I think there must be some different activity between the BTK inhibitors. It's a very interesting study. We just had the result and complete that paper.

I think it's really very important for all the physicians in China, because we have to face the same reality that many patients with B-cell lymphoma, they have the problem of HBV reactivation when they are under the anti-lymphoma or anti-lymphocytic leukemia treatment. We really need to know if the patients are safe or not when we give the treatment of the lymphoma.

Source:
Yang S, Zhu R, Li N, et al. Ibrutinib in Advanced Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: Lower Risk of Hepatitis B Virus Reactivation. Acta Haematol. 2022;145:54-62. doi:10.1159/000518398.