Farrukh Awan, MD

Farrukh Awan, MD, associate professor in the Department of Internal Medicine, UT Southwestern Medical Center (UTSW), and a member of the Division of Hematology and Oncology at UTSW's Harold C. Simmons Comprehensive Cancer Center and William P. Clements Jr. University Hospital, discusses remaining questions regarding the use of BTK inhibitors and CD20-directed monoclonal antibodies in chronic lymphocytic leukemia (CLL).

When determining whether to give a patient with CLL a BTK inhibitor alone or in combination with a CD20-directed antibody, it is important to have a discussion with patients, says Awan. During that conversation, the first question that is considered has to do with what benefit the patient can potentially derive from the addition of the CD20-directed antibody to the BTK inhibitor. Early data indicate that, at least with the addition of rituximab (Rituxan) to ibrutinib (Imbruvica), outcomes were not necessarily better than those observed with ibrutinib alone, says Awan. It should not be automatically assumed that the addition of a CD20-directed antibody to a BTK inhibitor will lead to longer remissions for patients, adds Awan.

In contrast, data from the CLL11 trial showed that obinutuzumab (Gazyva) outperformed rituximab, says Awan. As such, examining combinations with obinutuzumab made sense to examine in a clinical trial. Some emerging data suggest that there might be a trend toward improved outcomes when obinutuzumab is combined with acalabrutinib (Calquence) and possibly with ibrutinib. The field does not have the right trials to answer that specific question yet, concludes Awan.

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Farrukh Awan, MD, discusses remaining questions regarding the use of BTK inhibitors and CD20-directed monoclonal antibodies in chronic lymphocytic leukemia.

Dr. Awan on Remaining Questions With BTK Inhibitors and Anti-CD20 Combos in CLL

Farrukh Awan, MD, associate professor, Department of Internal Medicine, Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, discusses the future of combination therapies in chronic lymphocytic leukemia (CLL).

The advent of combination regimens in CLL was a popular topic of discussion at the 2019 ASH Annual Meeting, says Awan. The idea with all these studies, such as those evaluating the combination of venetoclax (Venclexta) and ibrutinib (Imbruvica) or venetoclax and acalabrutinib (Calquence), is to combine all these agents in a rational manner and use minimal residual disease as an end point.

If patients can be brought into a deep remission, in the peripheral blood or bone marrow, then those patients can discontinue therapy and, hopefully, sustain their remission for an extended period of time, explains Awan. This idea is very exciting but more follow-up is needed. Specifically, investigators want to understand what should be done if the disease returns. Can these agents be used as salvage therapy?

Some exciting emerging data suggest that there are ways to manage those patients safely, says Awan. The key takeaway is that all these options are in the process of being developed further, especially the combinations, and hopefully these efforts will result in the use of all these treatments either sequentially or concurrently to improve outcomes, concludes Awan.

Farrukh Awan, MD, discusses questions regarding combination therapies in chronic lymphocytic leukemia.

Dr. Awan on Future of Combo Regimens in CLL Treatment Paradigm

Farrukh Awan, MD, associate professor in the Department of Internal Medicine at UT Southwestern (UTSW) Medical Center, and member, Division of Hematology and Oncology at UTSW’s Harold C. Simmons Comprehensive Cancer Center and William P. Clements Jr. University Hospital, discusses novel approaches under investigation in relapsed/refractory chronic lymphocytic leukemia (CLL).

Many drugs are slowly making their way through the treatment pipeline, says Awan. For example, duvelisib (Copiktra) received approval from the FDA for use in adult patients with relapsed/refractory CLL or small lymphocytic leukemia who had received at least 2 prior therapies, says Awan.

Additionally, alternative BTK inhibitors are being explored in clinical trials. The rationale behind that research is that those drugs would be utilized in patients who develop resistance to ibrutinib (Imbruvica) or acalabrutinib (Calquence), explains Awan. This concept is particularly exciting because even if a patient progresses on a BTK inhibitor, that does not necessarily mean that other BTK inhibitors would not be effective options for them, says Awan.

Furthermore, UT Southwestern Medical Center has access to some trials examining triplets and CAR T-cell therapy. CAR T-cell therapy is a huge advancement in the CLL treatment paradigm, says Awan, and emerging data with this approach look promising. Ongoing trials are evaluating CAR T-cell therapy in patients who have failed all prior treatment; historically, this patient population has had dismal outcomes, says Awan.

This approach is particularly exciting because patients can potentially be cured without having to undergo an allogeneic stem cell transplant, says Awan. Although patients with relapsed/refractory disease are experiencing favorable responses with CAR T-cell therapy, more follow-up will be needed, concludes Awan.

Farrukh Awan, MD, discusses novel approaches under investigation in relapsed/refractory chronic lymphocytic leukemia.

Dr. Awan on Novel Strategies Under Exploration in Relapsed/Refractory CLL

Farrukh Awan, MD, associate professor, Department of Internal Medicine, UT Southwestern (UTSW) Medical Center, and member, Division of Hematology and Oncology, Harold C. Simmons Comprehensive Cancer Center and William P. Clements Jr. University Hospital, discusses the utilization of acalabrutinib (Calquence) in patients with chronic lymphocytic leukemia (CLL).

The phase III ASCEND trial compared acalabrutinib with chemoimmunotherapy in the relapsed/refractory setting and data showed that acalabrutinib was superior, explains Awan. Furthermore, for patients with treatment-naïve CLL, the phase III ELEVATE-TN trial compared acalabrutinib alone versus acalabrutinib plus obinutuzumab (Gazyva), versus obinutuzumab plus chlorambucil. The study showed that acalabrutinib alone or in combination with obinutuzumab has positive efficacy was superior to chlorambucil/obinutuzumab.

Acalabrutinib can be utilized in patients who may not be tolerant of ibrutinib (Imbruvica), according to Awan. Research has shown that patients who stop ibrutinib (Imbruvica) due to adverse events can safely continue on acalabrutinib in most situations, Awan concludes.

Farrukh Awan, MD, discusses the utilization of acalabrutinib in patients with chronic lymphocytic leukemia.

Author | Farrukh Awan, MD

Articles

Dr. Awan on Remaining Questions With BTK Inhibitors and Anti-CD20 Combos in CLL

Dr. Awan on Future of Combo Regimens in CLL Treatment Paradigm

Dr. Awan on Novel Strategies Under Exploration in Relapsed/Refractory CLL

Dr. Awan on Utilizing Acalabrutinib in CLL