Bruce G. Raphael, MD, a clinical professor in the Department of Medicine at NYU Langone Health, discusses the utility of venetoclax (Venclexta) and obinutuzumab (Gazyva) in chronic lymphocytic leukemia (CLL).

The CLL14 trial was one of the first trials to show that the combination of novel agents can provide a greater or more complete response than that achieved with standard regimens, says Raphael. In the trial, the BCL-2 inhibitor, venetoclax (Venclexta), was combined with obinutuzumab (Gazyva) and compared with the standard treatment comprised of chlorambucil and obinutuzumab.

After a median follow-up of 28.1 months, progression-free survival rate at 24 months was significantly higher in the venetoclax/obinutuzumab arm, at 88.2%, than in the chlorambucil/obinutuzumab arm, at 64.1%. The results of this trial are two-fold, says Raphael. In the 1 year of treatment, patients experienced higher rates of response with the venetoclax/obinutuzumab combination as well as higher levels of minimal residual disease negativity; this translated into better responses, particularly for high-risk patients, concludes Raphael.

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Bruce G. Raphael, MD, discusses the utility of venetoclax and obinutuzumab in chronic lymphocytic leukemia.

Dr. Raphael on the Clinical Implications of the CLL14 Trial

Bruce G. Raphael, MD, a clinical professor in the Department of Medicine at NYU Langone Health, discusses the risk of tumor lysis syndrome in chronic lymphocytic leukemia (CLL).

Sequencing is important because of the risk of tumor lysis syndrome (TLS). In the past, standard treatment options did not kill enough CLL cells, so TLS and its consequences were not understood as well. CLL is a slow disease, says Raphael. Now that more effective agents are available, particularly BCL-2 inhibitors, it is known that patients with a large tumor burden are more likely to develop TLS, particularly at the beginning of treatment, explains Raphael. In an effort to mitigate this, patients are now started on smaller doses of these agents, such as 20 mg. Then, the dose is increased to 400 mg over 1 to 2 months, adds Raphael.

However, if obinutuzumab (Gazyva) is used first, then there may be reduction of the tumor without TLS, adds Raphael. With other novel drug options, patients do not experience TLS. As such, in the protocol of an ECOG trial, all patients are started on obinutuzumab and ibrutinib(Imbruvica) and after 2 months of cytoreduction, venetoclax (Venclexta) is added, concludes Raphael.

Bruce G. Raphael, MD, discusses the risk of tumor lysis syndrome in chronic lymphocytic leukemia.

Dr. Raphael on Addressing the Risk of Tumor Lysis Syndrome in CLL

Bruce G. Raphael, MD, a clinical professor in the Department of Medicine at NYU Langone Health, discusses the phase II CLARITY trial in chronic lymphocytic leukemia (CLL).

The CLARITY trial showed that the combination of ibrutinib (Imbruvica) and venetoclax (Venclexta) was safe. The incidence of neutropenia associated with the regimen was well managed by preventing low neutrophils or by using filgrastim (Neupogen), says Raphael. Treatment with the combination also resulted in a high rate of minimal residual disease (MRD) negativity.

The results of the trial prompted the Eastern Cooperative Oncology Group (ECOG) to evaluate the combination plus obinutuzumab (Gazyva) versus obinutuzumab and ibrutinib. The treatment, which will be sequenced to prevent tumor lysis syndrome, may lead to a higher, and potentially more durable, rate of MRD-negative disease than what had been observed in the CLARITY trial, concludes Raphael.

Dr. Raphael on the CLARITY Trial in CLL

Bruce G. Raphael, MD, a clinical professor in the Department of Medicine at NYU Langone Health, discusses the treatment landscape of chronic lymphocytic leukemia (CLL).

Historically, CLL was thought to be a slow progressing disease for which symptom management was the only intervention, says Raphael.

However, novel agents including CD20-directed antibodies, BTK inhibitors, PI3K inhibitors, and BCL-2 targeted agents have demonstrated improved survival for patients compared with chemotherapy.

As a result, chemotherapy regimens like fludarabine/cyclophosphamide/rituximab (Rituxan; FCR) and bendamustine/rituximab have become less widespread in the treatment of patients with CLL, explains Raphael. Now, the field is working to define the combinations that will elicit the greatest response for patients, concludes Raphael.

Bruce G. Raphael, MD, discusses the treatment landscape of chronic lymphocytic leukemia.



Bruce G. Raphael, MD

Articles

Dr. Raphael on the Clinical Implications of the CLL14 Trial

Dr. Raphael on Addressing the Risk of Tumor Lysis Syndrome in CLL

Dr. Raphael on the CLARITY Trial in CLL

Dr. Raphael on the Treatment Landscape of CLL