Accreditation/Credit Designation

Physicians’ Education Resource®, LLC, is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

Physicians’ Education Resource®, LLC, designates this enduring material for a maximum of 0.5 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Acknowledgement of Commercial Support

This activity is supported by an educational grant from Gilead Sciences, Inc.

Cancer Summaries and Commentaries™: Update from Atlanta: Advances in the Treatment of Chronic Lymphocytic Leukemia

Release Date: February 28, 2018
Expiration Date: February 28, 2019
Media: Internet - based


Activity Overview

This online activity is designed to update physicians on data presented at the 59th ASH Annual Meeting & Exposition, held in Atlanta in December 2017, to facilitate critical assessment and, when appropriate, clinical integration of new evidence on chronic lymphocytic leukemia (CLL). The activity reviews 4 clinically intriguing abstracts from the meeting selected by the program faculty, Susan O’Brien MD. For each abstract, a short summary of key clinical data is accompanied by faculty commentary that provides insight into how new data fit into the current field, and how clinicians may apply relevant findings to their clinical practice to improve patient care. Interactive questions are interspersed throughout the activity to enable engagement, learning, and self-assessment.

Acknowledgement of Commercial Support

This activity is supported by an educational grant from Gilead Sciences, Inc.

CME Activity Table of Contents

  • Initial Results of Ibrutinib Plus Venetoclax in Relapsed, Refractory CLL (Bloodwise TAP CLARITY Study)
  • Venetoclax Plus Rituximab Is Superior to Bendamustine Plus Rituximab in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia: Results From Pre-Planned Interim Analysis of the Randomized Phase III MURANO Study
  • Evaluating the Efficacy, Safety, and Dose-Dependent Activities of Entospletinib in Patients With Chronic Lymphocytic Leukemia
  • Multicentre Retrospective Analysis of Chronic Lymphocytic Leukaemia Patients Treated with Idelalisib; “Real-World” Data from the UK and Republic of Ireland– A Cohort of 68 Patients

Instructions for This Activity and Receiving Credit

  • You will need to login to participate in the activity.
  • Each presentation may contain an interactive question(s). You may move forward through the presentation; however, you may not go back to change answers or review videos/content until you finish the presentation.
  • At the end of the activity, “educational content/video files” will be available for your reference.
  • In order to receive a CME certificate, participants must complete the activity.
  • Complete the posttest and pass with a score of 70% or higher, complete the evaluation and then click on request for credit. Participants may immediately download a CME certificate upon completion of these steps.

Target Audience

This activity is directed toward medical oncologists who treat patients with CLL. Fellows, nurses, nurse practitioners, physician assistants, and other healthcare professionals involved in the management of patients with CLL are also invited to participate.

Learning Objectives

At the conclusion of this activity, you should be better prepared to:

  • Detail the design and primary outcome measures of completed and ongoing clinical studies in patients with CLL
  • Explain recent clinical trial results regarding novel approaches for patients with CLL
  • Place presented trial evidence into the context of evolving treatment paradigms and sequencing strategies for the management of patients with CLL

Faculty, Staff, and Planners' Disclosures


Susan O’Brien, MD
Associate Director for Clinical Sciences
Chao Family Comprehensive Cancer Center
Medical Director
Sue and Ralph Stern Center for Clinical Trials & Research
Professor of Medicine
Division of Hematology/Oncology
Department of Medicine
University of California, Irvine
Irvine, CA

Disclosure:Consultant: Amgen, Astellas, Celgene, GlaxoSmithKline, Janssen Oncology, Aptose Biosciences Inc., Vaniam Group LLC, AbbVie, Alexion; Research Support: Kite, Regeneron, Acerta; Consultant/Research Support: Gilead, Pharmacyclics, TG Therapeutics, Pfizer, Sunesis.

The staff of PER® have no relevant financial relationships with commercial interests to disclose.

Disclosure Policy and Resolution of Conflicts of Interest (COI)

As a sponsor accredited by the ACCME, it is the policy of PER® to ensure fair balance, independence, objectivity, and scientific rigor in all of its CME activities. In compliance with ACCME guidelines, PER® requires everyone who is in a position to control the content of a CME activity to disclose all relevant financial relationships with commercial interests. The ACCME defines “relevant financial relationships” as financial relationships in any amount occurring within the past 12 months that creates a COI.

Additionally, PER® is required by ACCME to resolve all COI. PER® has identified and resolved all COI prior to the start of this activity by using a multistep process.

Off-Label Disclosure and Disclaimer

This CME activity may or may not discuss investigational, unapproved, or off-label use of drugs. Participants are advised to consult prescribing information for any products discussed. The information provided in this CME activity is for continuing medical and nursing education purposes only, and is not meant to substitute for the independent clinical judgment of a physician relative to diagnostic, treatment, or management options for a specific patient’s medical condition. The opinions expressed in the content are solely those of the individual faculty members and do not reflect those of PER®.

PER Pulse ™ Recap

Pulse Recap (1 of 3)

What have we learned about the combination of ibrutinib and venetoclax in the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL)?

The CLARITY trial was designed to assess the combination of venetoclax, a BCL-2 inhibitor, and ibrutinib, a Bruton tyrosine kinase inhibitor, in the treatment of patients with R/R CLL.1 Approximately 20,940 new cases of CLL are expected to be diagnosed this year.2 Both agents have been approved as monotherapy in CLL, and the combination has been shown to have a synergistic effect based upon preclinical data.3

The CLARITY study enrolled 54 patients with CLL who had either relapsed within 3 years of fludarabine, cyclophosphamide, and rituximab, or bendamustine plus rituximab, or had a 17p deletion and did not respond to ≥1 lines of therapy.1 The primary endpoint of the study was the eradication of minimal residual disease (MRD) in the marrow (<1 CLL cell in 104 after 12 months of ibrutinib and venetoclax).1

In the CLARITY study, after 8 weeks of treatment with ibrutinib alone, patients underwent a dose escalation of venetoclax (combined with ibrutinib). One patient developed tumor lysis syndrome, which was managed with dose interruption of venetoclax with subsequent escalation to the target dose of 400 mg.1 The combination was generally well tolerated. Neutropenia and bruising were commonly reported.1

After 6 months of the combination of ibrutinib plus venetoclax, 84% of patients had normal trephine biopsy. The overall response rate was noted to be 100%. Of the 38 patients who had at least 6 months of combination treatment, 37% achieved peripheral blood MRD negativity and 32% achieved bone marrow MRD negativity.1

  1. Hillmen P, Munir T, Rawstron A, et al. Initial results of ibrutinib plus venetoclax in relapsed, refractory CLL (Bloodwise TAP CLARITY study): high rates of overall response, complete remission and MRD eradication after 6 months of combination therapy. Presented at: the American Society of Hematology 59th Annual Meeting & Exposition; December 9-12, 2017; Atlanta, GA. Abstract 428.
  2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68(1):7-30. doi: 10.3322/caac.21442.
  3. Cervantes-Gomez F, Lamothe B, Woyach JA, et al. Pharmacological and protein profiling suggest venetoclax (ABT-199) as optimal partner with ibrutinib in chronic lymphocytic leukemia. Clin Cancer Res. 2015;21(16):3705-3715. doi: 10.1158/1078-0432.CRR-14-2809.

Pulse Recap (2 of 3)

What is the potential of venetoclax and rituximab in the treatment of patients with R/R CLL?

Venetoclax has been shown to have efficacy in the treatment of patients with R/R CLL, even those with a 17p deletion.1 It has been used as monotherapy, and the combination of this treatment with other options as a means of improving clinical outcomes remains an active area of investigation.2

The phase III MURANO study enrolled 389 patients with R/R CLL who had received 1 to 3 previous lines of therapy, at least 1 of which contained chemotherapy. Patients were randomized 1:1 to receive either venetoclax plus rituximab or bendamustine plus rituximab.3 The primary endpoint was investigator-assessed progression-free survival (PFS).

At the time of data cutoff, the investigator-assessed PFS was significantly greater for patients receiving venetoclax/rituximab compared with those receiving bendamustine/rituximab (median not reached vs 17.0 months; HR, 0.17; 95% CI, 0.11-0.25; P <.0001).3 The 24-month PFS estimates were 84.9% for patients receiving venetoclax/rituximab versus 36.3% in patients receiving bendamustine/rituximab. Improvements with venetoclax/rituximab were also noted in overall survival relative to patients receiving bendamustine/rituximab (HR, 0.48; 95% CI, 0.25-0.90). The investigator-assessed ORR was 93.3% in the venetoclax arm compared with 67.7% in the bendamustine arm. The MRD negativity rates were greater in the venetoclax arm (83.5% vs 23.1%), as was the durability of the MRD negativity.3

There were 6 grade ≥3 TLS adverse events (AEs) in the venetoclax arm compared with 2 in the bendamustine arm. Richter transformation was established in 6 patients in the venetoclax arm and in 5 in the bendamustine arm. AEs associated with death were observed in 5.2% of patients in the venetoclax arm compared with 5.9% in the bendamustine arm.

  1. Stilgenbauer S, Eichhorst B, Schetelig J, et al. Venetoclax in relapsed or refractory chronic lymphocytic leukaemia with 17p deletion: a multicentre, open-label, phase 2 study. Lancet Oncol. 2016;17(6):768-778. doi: 10.1016/S1470-2405(16)30019-5.
  2. Crombie J, Davids MS. Venetoclax for the treatment of patients with chronic lymphocytic leukemia. Future Oncol. 2017;13(14):1223-1232. doi: 10.2217/fon-2017-0031.
  3. Seymour JF, Kipps TJ, Eichhorst BF, et al. Venetoclax plus rituximab is superior to bendamustine plus rituximab in patients with relapsed/refractory chronic lymphocytic leukemia – results from pre-planned interim analysis of the randomized phase III MURANO study. Presented at: the American Society of Hematology 59th Annual Meeting & Exposition; December 9-12, 2017; Atlanta, GA. Abstract LBA-2.

Pulse Recap (3 of 3)

What has real-world evidence for idelalisib shown in patients with CLL?

Although idelalisib has been approved in combination with rituximab for the treatment of patients with R/R CLL since 2014, there is a relative dearth of real-world data assessing the efficacy and safety of idelalisib in patients outside the parameters of clinical trial populations.1 Many clinical trials do not have cohorts that reflect the population of patients with CLL in the community.2 A retrospective analysis of patients who were treated between April 2013 and July 2017 for CLL was conducted to provide such information.

The median patient age was 77 years, and patients had received a median of 2 prior therapies. Many patients had poor prognostic disease, including TP53-mutated or 17p-, 11q-, or ATM-deleted disease.1 The median duration of treatment for this cohort was 12 months, with 16 of 68 patients completing ≥2 years of treatment. Three patients did not respond to idelalisib therapy. The median reported event-free survival (death, progression, or treatment discontinuation) was 15 months, with 44 of 68 patients remaining on therapy at 12 months and 15 of 68 patients remaining on treatment after ≥24 months.1

Drug toxicity led to treatment interruption in 32 of 68 cases, with a median value of 1 drug interruption and median duration off therapy of 30 days. Idelalisib was discontinued in 37 of 68 patients (12 due to progression; 13, diarrhea/colitis; 6, recurrent infection; 4, pneumonitis; and 2, hepatotoxicity). A single therapy-related death occurred in a patient receiving idelalisib.1

  • Idelalisib and rituximab is an active combination in CLL, and may be well tolerated even among older patients.
  1. Fernando F, Griffin J, Taylor J, et al. Multicentre retrospective analysis of chronic lymphocytic leukaemia patients treated with idelalisib, “real world” data from the UK and Republic of Ireland – a cohort of 68 patients. Presented at: the American Society of Hematology 59th Annual Meeting & Exposition; December 9-12, 2017; Atlanta, GA. Abstract 1733.
  2. Nabhan C, Mato A, Flowers CR, et al. Characterizing and prognosticating chronic lymphocytic leukemia in the elderly: prospective evaluation on 455 patients treated in the United States. BMC Cancer. 2017;17(1):198. doi: 10.1186/s12885-017-3176-x.

What have data told us about the potential for entospletinib use in patients with CLL?

A recent study yielded promising results for the novel formulation of entospletinib at different dosages. The 3 dosages assessed (100 mg, 200 mg, and 400 mg) produced comparable values for median progression-free survival (PFS).1 At the 400-mg dosage, there were no increases in significant toxicities relative to lower dosages, whereas there were increases in the 6-month PFS rate, overall response rate, and median duration of exposure in patients receiving 400 mg.1

  • Entospletinib is a well-tolerated molecule that is moving forward in combination treatments for patients with CLL.
  1. Sharman JP, Kolibaba KS, Azar J, et al. Evaluating the efficacy, safety, and dose dependent activities of entospletinib in patients with chronic lymphocytic leukemia. Presented at: the American Society of Hematology 59th Annual Meeting & Exposition; December 9-12, 2017; Atlanta, GA. Abstract 832.

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