William G. Wierda, MD, PhD, medical director, Leukemia Center, The University of Texas MD Anderson Cancer Center, discusses resistance to ibrutinib in patients with chronic lymphocytic leukemia (CLL).

Not many patients are resistant to ibrutinib, Wierda explains. However, approximately 30-40% of patients who develop resistance have Richter’s transformation, and will likely require more aggressive treatment. Other patients may discontinue treatment due to toxicity.

 mutations can occur, which render resistance to ibrutinib. Regarding standard clinical use of the drug, Wierda says there is no need to monitor for these mutations nor adjust treatment for it, though data should be collected.

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William G. Wierda, MD, PhD, medical director, Leukemia Center, The University of Texas MD Anderson Cancer Center, discusses resistance to ibrutinib in patients with chronic lymphocytic leukemia (CLL). 

Dr. Wierda on Ibrutinib Resistance in CLL

William G. Wierda, MD, PhD, medical director of the Leukemia Center at The University of Texas MD Anderson Cancer Center in Houston, discusses upcoming RESONATE-2 trial results for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

RESONATE-2 is a phase III, randomized, multicenter, open-label study of elderly patients with CLL or SLL comparing ibrutinib to chlorambucil. In initial reports, Wierda expects results to demonstrate improved progression-free survival outcomes in patients receiving ibrutinib in the frontline setting. He predicts toxicity and tolerability will also improve.

It may be quite some time before overall survival differences are demonstrated, because patients can be salvaged with ibrutinib following chlorambucil, Wierda says.

This is based on findings in the RESONATE trial and similar single-arm trials with ibrutinib. 

William G. Wierda, MD, PhD, medical director of the Leukemia Center at The University of Texas MD Anderson Cancer Center in Houston, discusses upcoming RESONATE-2 trial results for patients with chronic lymphocytic leukemia (CLL). 

Dr. Wierda on RESONATE-2 Trial Predictions for Patients With CLL

	William G. Wierda, MD, PhD, medical director of the Leukemia Center at The University of Texas MD Anderson Cancer Center in Houston, discusses the different standard frontline therapies for patients with chronic lymphocytic leukemia (CLL).

	Wierda says chemotherapy is the standard of care for frontline treatment except for patients who are untreated and harbor the 17p deletion mutation. These patients would receive ibrutinib as frontline therapy, Wierda says.

	For patients who are  young and fit, fludarabine/cyclophosphamide/rituximab (FCR) is favored over  bendamustine/rituximab (BR), Wierda says.

	For patients over 65 or those who are frail or have comorbidities, Wierda suggests using chlorambucil plus obinituzumab is as frontline therapy. Wierda says chlorambucil plus ofatumumab is another option since it is superior in terms of progression-free survival, but chlorambucil plus obinituzumab is superior in overall survival. 

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William G. Wierda, MD, PhD, medical director of the Leukemia Center at The University of Texas MD Anderson Cancer Center in Houston, discusses the different standard frontline therapies for patients with chronic lymphocytic leukemia. 

Dr. Wierda on Frontline Therapy for Older CLL Patients Compared to Younger

William G. Wierda, MD, PhD, professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses treatment options for patients with CLL who harbor the 17p deletion.

Wierda says CLL patients who have been previously treated and have a 17p deletion are the highest risk group of patients. Untreated CLL patients who harbor the 17p deletion, a small minority of patients going on frontline therapy, have a short first remission if they respond well to standard treatment. However, the majority of these patients do not experience complete remissions and their disease is not held in check for long, Wierda says.

Physicians do not have much experience in treating previously untreated 17p deletion patients with ibrutinib. However, Wierda says these patients may benefit the most from frontline ibrutinib, as early data have shown that ibrutinib improves the survival of relapsed patients.

Weirda believes that there is no standard treatment for CLL patients who harbor the 17p deletion.

Dr. Wierda on Treating CLL Patients with 17p Deletion

William G. Wierda, MD, PhD, professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses treatment recommendations for patients with chronic lymphocytic leukemia (CLL).

The CLL11 trial compared chlorambucil, chlorambucil plus rituximab, and chlorambucil plus obinutuzumab (GA101) in previously untreated patients with CLL and and preexisting medical conditions. The trial showed superiority for the chlorambucil plus obinutuzumab arm. To be eligible for this trial, patients needed to have a SEER score higher than 6, which reflects comorbidities associated with age (over age 65 or 70) or renal insufficiency.

Wierda says if an elderly patient who needs frontline therapy and is not appropriate for chemoimmunotherapy is seen at his practice, the first choice of treatment for the patient would be chlorambucil plus obinutuzumab.

William G. Wierda, MD, PhD, professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses treatment recommendations for patients with CLL.

Dr. Wierda on the Treatment of Elderly CLL Patients

William G. Wierda, MD, PhD, associate professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, explains that the standard initial treatment for patients with asymptomatic chronic lymphocytic leukemia (CLL) is watchful waiting.

Clinical trials have not illuminated a clear improvement in outcomes linked to providing earlier treatments for CLL, when compared to observation alone. In general, the risks of receiving a treatment outweighed the potential benefits. As a result, the first-line therapy is generally administered following the development of certain indications, such as bone marrow failure, which is reflected by low hemoglobin or platelets counts.

Wierda notes that watchful waiting has been the first step in CLL treatment for many years and will continue to be the best place to start for many patients, until another option becomes available.

Dr. William Wierda, from the MD Anderson Cancer Center, Discusses Watchful Waiting in CLL

Dr. Wierda Discusses Watchful Waiting in CLL

William G. Wierda, MD, PhD, associate professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, discusses the standard diagnostic workup for patients with chronic lymphocytic leukemia (CLL), a type of leukemia that is characterized by lymphocyte overproduction.

The first step in the examination of a potential patient with CLL is to send a blood sample for flow cytometry (FCM). The results of this test will help characterize the lymphocyte population. Initially patients will be referred after a blood count has demonstrated elevated white cells or unusually high lymphocytes; FCM checks if these cells are neoplastic.

CLL cells are generally monoclonal and express CD5, CD19, and CD23. The identification of these markers is required to make a diagnosis. The use of fluorescent in situ hybridization is not needed to make a diagnosis and can be reserved until later to detect prognostic markers.

Prognostic factors are informative and helpful for counseling the patients and determining the frequency of follow up after diagnosis. However, in the watch and wait phase the prognostic factors supply additional information that isn't primarily used to manage patients.

Dr. William Wierda, from MD Anderson Cancer Center, on Diagnosing Chronic Lymphocytic Leukemia

William G. Wierda, MD, PhD

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