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.

Acknowledgment of Commercial Support

This activity is supported by educational grants from AbbVie and Bayer HealthCare Pharmaceuticals.

Community Practice Connections™: 3rd Annual European Congress on Hematology™: Focus on Lymphoid Malignancies

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

Activity Overview

Community Practice Connections™: 3rd Annual European Congress on Hematology™: Focus on Lymphoid Malignancies consists of a series of interactive clinical vignettes, short video interviews with leading experts in lymphoid malignancies, and brief summaries of clinical data related to these issues. The video interviews address decision points in the clinical vignettes, as well as questions commonly faced in the community oncology practice setting.

Acknowledgment of Commercial Support

This activity is supported by educational grants from AbbVie and Bayer HealthCare Pharmaceuticals.

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 educational activity is directed toward medical oncologists and other healthcare professionals (physicians, physicians-in-training, oncology nurses, pharmacists, and physician assistants) involved in the treatment and management of patients with hematologic malignancies.

Learning Objectives

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

  1. Appraise testing strategies that may inform clinical decision-making in the management of hematologic malignancies
  2. Apply clinical trial results to multiple lines of care in the management of hematologic malignancies
  3. Outline strategies to monitor and proactively manage treatment-related toxicities in patients with leukemia, lymphoma, and multiple myeloma
  4. Identify key emerging data pertaining to the diagnosis and management of patients with hematologic malignancies

Faculty, Staff, and Planners' Disclosures

Faculty

Renier J. Brentjens
Renier J. Brentjens, MD, PhD
Director, Cellular Therapeutics Center
Memorial Sloan Kettering Cancer Center
New York, NY

Disclosures: Grant/Research Support: Juno Therapeutics; Consultant: Juno Therapeutics

Peter Hillmen
Peter Hillmen, MB ChB, PhD
Professor of Experimental Hematology
University of Leeds
Leeds, United Kingdom

Disclosures: Grant/Research Support: AbbVie, Janssen, Pharmacyclics, Gilead, Roche, GlaxoSmithKline; Speakers Bureau: AbbVie, Janssen, Gilead, GlaxoSmithKline

María-Victoria Mateos
María-Victoria Mateos, MD, PhD
Associate Professor of Hematology
University Hospital of Salamanca
Salamanca, Spain

Disclosures: Grant/Research Support: Celgene; Consultant: Celgene, Janssen, Amgen, Takeda, AbbVie

Gilles A. Salles
Gilles A. Salles, MD, PhD
University Professor
Head of Hematology
Université Claude Bernard Lyon-1
Hospices Civils de Lyon
Lyon, France

Disclosures: Grant/Research Support: Roche; Consultant: Amgen, Bristol-Myers Squibb, Celgene, Gilead, Janssen, Kite Pharma, Merck, MorphoSys, Novartis, Roche, Servier

Anas Younes
Anas Younes, MD
Professor and Chief, Lymphoma Service
Division of Hematologic Oncology
Memorial Sloan Kettering Cancer Center
New York, NY

Disclosures: Grant/Research Support: Novartis, Johnson & Johnson, Curis, Roche, Bristol-Myers Squibb; Consultant: Bayer, Bristol-Myers Squibb, Celgene, Incyte, Janssen, Sanofi, Seattle Genetics, Takeda, Millennium, Genentech, Merck

The staff of Physicians' Education Resource®, LLC, (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 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™

PER Pulse Recap (1 of 3)

Insight from Anas Younes, MD – PER Pulse™ Recap: 3rd Annual European Congress on Hematology™: Focus on Lymphoid Malignancies

The live continuing medical education (CME) activity, 3rd Annual European Congress on Hematology™: Focus on Lymphoid Malignancies, was held October 12-13, 2018, in Paris, France. Program Chair Dr. Anas Younes and Co-Chairs Dr. Paolo Ghia and Dr. Gilles A. Salles were joined by faculty experts in the management of diffuse large B-cell lymphoma, CAR T-cell therapies, Hodgkin lymphoma (HL), follicular lymphoma, multiple myeloma, mantle cell lymphoma, and chronic lymphocytic leukemia to discuss practice-changing evidence and recommendations for integrating those findings into the clinical context.

This first of 3 PER Pulse™ Recaps will focus on treatment options for patients with classical HL (cHL) in the frontline and relapsed/refractory (R/R) settings. Below are some highlights from the activity.

For patients with HL, significant progress in treatment options and corresponding survival outcomes over the past few decades have led to permanent remissions and the disease being considered cured in approximately 80% to 90% of patients.1 However, treatment of R/R HL is clinically challenging, with multiple treatment options that include chemotherapy regimens, autologous stem cell transplantation (ASCT), antibody-drug conjugates, immune checkpoint inhibitors, and novel agents to be considered.

“Now we have multiple options for the treatment of patients with relapsed and refractory Hodgkin lymphoma, especially those who fail after autologous transplant. In the old days, the first thing that came to mind was allo transplant; nowadays there are options that can prolong life, with very good quality of life, including checkpoint inhibitors and brentuximab vedotin.”
 — Anas Younes, MD

In the frontline setting, in patients with advanced-stage disease, a recent randomized trial showed an improved 2-year modified progression-free survival (mPFS) following treatment with brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) compared with standard doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) therapy.

ECHELON-1 Trial
In the multicenter phase III ECHELON-1 trial,2 1334 patients with previously untreated stage III or IV cHL were randomized to receive treatment with ABVD (n=664) or A+AVD (n=670). The primary endpoint was mPFS, which was defined as time to disease progression, death, or modified progression (evidence of noncomplete response following completion of frontline therapy according to an independent committee review, followed by subsequent anticancer therapy).

At a median follow-up of 24.6 months, the 2-year rate of mPFS in the A+AVD treatment arm was significantly increased (82.1%; 95% CI, 78.8-85.0) versus (77.2%; 95% CI, 73.7-80.4) in the ABVD group (HR, 0.77; 95% CI, 0.60-0.98; P =.04).

Nearly all patients in both groups (99%, 98%) reported adverse events (AEs) of any grade (Table 1). Grade ≥3 AEs, serious AEs, and rates of grade ≥3 neutropenia were higher in the A+AVD group. Adverse events resulting in drug discontinuation and deaths during treatment were higher in the ABVD group. ESMO guidelines suggest that a longer follow-up is required before final conclusions are reached in terms of the A+AVD regimen.1

Table 1. ECHELON-1: Safety Findings

  A+AVD (N=662)
no. (%)
ABVD (N=659)
no. (%)
Any AE 653 (99) 646 (98)
Grade ≥3 AE 549 (83) 434 (66)
Serious AE 284 (43) 178 (27)
AE resulting in drug discontinuation 88 (13) 105 (16)
Death during treatmenta 9 (1) 13 (2)
Death due to drug-related AEs 8 (1) 7 (1)
Grade ≥3 neutropenia 357 (54) 260 (39)
Grade ≥3 peripheral sensory neuropathy 31 (5) 3 (<1)
a Death during treatment was defined as a death occurring within 30 days following the last dose of frontline therapy.
A+AVD indicates brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine; ABVD, doxorubicin, bleomycin, vinblastine, and dacarbazine; AE, adverse event.

References

  1. Eichenauer DA, Aleman BMP, André M, et al. Hodgkin lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018;29:iv19-iv29. doi: 10.1093/annonc/mdy080.
  2. Connors JM, Jurczak W, Straus DJ, et al. Brentuximab vedotin with chemotherapy for stage III or IV Hodgkin's lymphoma. N Engl J Med. 2018;378:331-344. doi: 10.1056/NEJMoa1708984.

PER Pulse Recap (2 of 3)

As a follow-up to the online continuing medical education (CME) activity, 3rd Annual European Congress on Hematology™: Focus on Lymphoid Malignancies, this second of 3 PER Pulse™ Recaps will focus on the role of targeted therapies in the treatment of relapsed/refractory chronic lymphocytic leukemia (R/R CLL). Below are some highlights from the activity.

In many cases, patients with asymptomatic relapsed CLL can be followed without therapy for a considerable time. For patients requiring treatment, if the relapse occurs within 24-36 months after chemoimmunotherapy, or in cases where the disease does not respond to any first-line therapy, changing the therapeutic regimen is recommended. Therapeutic options [III,B] include treatment with the BTK inhibitor ibrutinib, PI3K inhibitor idelalisib plus rituximab, or venetoclax (if patient failed BCR inhibitor therapy).1

“The key message is we’ve changed the treatment of CLL. We are really moving towards targeted therapies. In relapsed disease, we should be using either targeted treatments against proliferation – so ibrutinib predominantly, or therapies against apoptosis – venetoclax.”
 — Peter Hillmen, MB, ChB, PhD

MURANO Trial
In the international, open-label, phase III MURANO trial,2 389 patients with R/R CLL were randomized to receive treatment with venetoclax plus rituximab (VR) versus bendamustine plus rituximab (BR). The primary endpoint was investigator-assessed progression-free survival (PFS). After a median follow-up of 23.8 months, the rate of investigator-assessed PFS was significantly increased in the VR group (Table 1).

Table 1. MURANO: Key Efficacy and Safety Outcomes2

  VR (N=194) BR (N=195) HR (95% CI) P Value
2-year PFS rate, % 84.9 36.3 0.17; (0.11-0.25) P <.0001
Subgroup; with 17p del 81.5 27.8 0.13; (0.05-0.29)  
Subgroup; without 17p del 85.9 41.0 0.19; (0.12-0.32)  
ORR, % 92.3 72.3    
MRDa negative at 9-month assessmentb, no. (%) 121 (62.4) 26 (13.3)    
MRDa negative at any time during trialb, no. (%) 162 (83.5) 45 (23.1)    
  VR (N=194) BR (N=188)    
Grade ³3 AE, no. (%) 159 (82.0) 132 (70.2)    
Neutropenia 112 (57.7) 73 (38.8)    
Tumor lysis syndrome 6 (3.1) 2 (1.1)    
aThe threshold for MRD was 1 tumor cell per 104 white cells. Results below this threshold were deemed negative.
bThe absolute difference between the treatment groups in the rate of clearance of MRD was 49.0 percentage points (95% CI, 40.4-57.6) at the time of the 9-month combination-treatment response assessment visit and 60.4 percentage points (95% CI, 52.3-68.6) at any time during the trial.
AE indicates adverse event; BR, bendamustine plus rituximab; HR, hazard ratio; MRD, minimal residual disease; ORR, objective response rate; PFS, progression-free survival; VR, venetoclax plus rituximab.

Minimal residual disease eradication with VR combination therapy in patients with R/R CLL has demonstrated high durability, regardless of risk factors. Redevelopment of MRD-positive status (intermediate 10-4 to <10-2 range) occurs infrequently and may not result in clinical progressive disease.3 The European Commission recently approved venetoclax in combination with rituximab for the treatment of patients with R/R CLL following at least 1 prior line of therapy.

References

  1. European Society for Medical Oncology. eUpdate – Chronic Lymphocytic Leukaemia Treatment Recommendations. https://www.esmo.org/Guidelines/Haematological-Malignancies/Chronic-Lymphocytic-Leukaemia/eUpdate-Treatment-Recommendations. Accessed November 6, 2018.
  2. Seymour JF, Kipps TJ, Eichhorst B, et al. Venetoclax-rituximab in relapsed or refractory chronic lymphocytic leukemia. N Engl J Med. 2018;378:1107-1120. doi: 10.1056/NEJMoa1713976.
  3. Hillmen P, Seymour JF, Langerak AW, et al. High durable minimal residual disease (MRD) negativity with venetoclax + rituximab in relapsed/refractory CLL: MRD kinetics and responses in cytogenetic risk groups in pts from phase 3 MURANO study. Presented at the 2018 European Hematology Association Congress; June 14-17, 2018; Stockholm, Sweden. Abstract S805.

PER Pulse Recap (3 of 3)

As a follow-up to the online continuing medical education (CME) activity, 3rd Annual European Congress on Hematology™: Focus on Lymphoid Malignancies, this third of 3 PER Pulse™ Recaps will focus on the treatment options for patients with follicular lymphoma in the frontline and relapsed/refractory (R/R) settings. Below are some highlights from the activity.

In Western Europe, the second most common lymphoma diagnosed is follicular lymphoma (FL), with a rising annual incidence since the 1950s.

ESMO guideline-preferred first-line therapy for patients with non-bulky stage I–II FL is radiotherapy (RT; involved field, 24 Gy), potentially providing patients with a curative outcome [II, B]. In certain cases (eg, abdominal: mucositis; cervical: sicca syndrome, hypothyroidism, or myeloablative suppression), watchful waiting or monotherapy treatment with rituximab may be viable options to avoid the side effects of RT. For patients with stage I-II disease with large tumor burden, systemic therapy is indicated [IV, B]. Where complete remission and long PFS is the treatment goal, first-line therapy for patients with stage III-IV FL includes R-CHOP or rituximab plus bendamustine [I, B].1

“If at relapse, the patient has retained follicular lymphoma histology, there are different options. These include watching the patient, using rituximab single-agent, radiation therapy, starting a new chemo regimen plus anti-CD20, discussing transplant options for some patients, but also discussing innovative therapy, within clinical trials or based on the recent approvals of some new agents, including PI3 kinase inhibitors.”
 — Gilles A. Salles, MD, PhD

At the time of relapse, a new biopsy is strongly recommended to rule out transformation of FL into a more aggressive form of lymphoma. ESMO consensus-driven recommendations outside of clinical trials provide guidance for treatments at relapse. For patients with a low tumor burden at relapse, watch and wait and chemoimmunotherapy are treatment options. For patients with a high tumor burden at relapse, chemoimmunotherapy +/- rituximab maintenance or radioimmunotherapy are treatment options. For double-refractory patients, treatment with the PI3K inhibitor idelalisib is a treatment option.1

References

  1. Dreyling M, Ghielmini M, Rule S, et al. Newly diagnosed and relapsed follicular lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016;27(suppl 5):v83-v90. https://doi.org/10.1093/annonc/mdw400. Correction: Ann Oncol. 2017;28(12):3109. https://doi.org/10.1093/annonc/mdx020.

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