Haematological Malignancies, Haematology, Lymphoma CME ACCREDITED Watch Time: 40 mins

touchEXPERT OPINIONS New and emerging strategies for managing patients with relapsed/refractory follicular lymphoma: latest advances in prognostics and treatment

Watch leading lymphoma specialists provide updates on prognostic factors and novel treatment strategies for patients with relapsed/refractory follicular lymphoma

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Prof. Kami Maddocks
The Ohio State University, Columbus, OH, USA
How can we best utilize prognostic factors to identify patients with FL at risk of the poorest outcomes?

Prof. Maddocks describes the key prognostic factors that indicate high risk of inferior outcomes in patients with FL

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Interview Questions

In this interview, Prof. Maddocks answers the following questions:

  • What are the key prognostic scoring systems used at initial diagnosis of FL and what are their advantages versus limitations?
  • How is PET/CT used prior to treatment of FL and how might measurement of total metabolic tumor volume aid prognosis?
  • What are the key parameters used as prognostic factors after initial treatment of FL?
  • Based on ongoing research into novel prognostic factors for FL, what key parameters may have prognostic value in future clinical practice?
  • How can the way prognosis is assessed in patients with FL be improved upon in future?
About Prof. Kami Maddocks

Dr Kami Maddocks is a Professor of Clinical Internal Medicine and Director of the Lymphoma Program in the Division of Hematology at The Ohio State University. She works as a hematologist specializing in treating patients with B-cell malignancies, including non-Hodgkin’s lymphoma, Hodgkin’s lymphoma and chronic lymphocytic leukemia. Dr Maddocks conducts research on new therapies for these hematologic malignancies, largely through evaluating new targeted therapies in clinical trials. She has particular interest in aggressive lymphomas, including mantle cell lymphoma (MCL).read more

Dr Maddocks received her medical degree from the University of South Dakota, followed by an internal medicine internship and residency at Mayo Clinic Rochester, Minnesota. She completed her fellowship in hematology/oncology at The Ohio State University. She has board certification in internal medicine, medical oncology and hematology.

Dr Maddocks is an investigator on several clinical trials in lymphoma, most of which are evaluating non-chemotherapeutic approaches to the treatment of lymphoma. She serves on the Alliance Lymphoma Committee, a multi-institution working group to develop clinical trials in lymphoma and she is the Alliance Chair on two MCL trials through Alliance Foundation Trials and National Clinical Trials Network. Over the years, Dr Maddocks has been very involved with philanthropic efforts through the Leukemia and Lymphoma Society and Pelotonia.

Professor Kami Maddocks discloses: Research funding from Bristol Myers Squibb, Merck, Novartis and Pharmacyclics. Consulting fees from ADC Therapeutics, Beigene, Celgene, Janssen, Karyopharm, Kite, Morphosys, Pharmacyclics and Seattle Genetics.

 
Dr Connie Lee Batlevi
Memorial Sloan Kettering Cancer Centre, New York, USA.
With novel treatments now available and several in development, is there new hope for patients with R/R FL?

Dr Batlevi reviews the novel and emerging treatment strategies for patients with R/R FL

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Interview Questions

In this interview, Dr Batlevi answers the following questions:

  • What new approaches to the treatment of patients with R/R FL have emerged in recent years?
  • What PI3K inhibitors are available for the treatment of R/R FL and how do they differ?
  • Why is EZH2 an attractive target for FL therapy and what EZH2 inhibitors are available?
  • Why are CD19 CAR T cells promising emerging therapies for R/R FL and what are the key agents in development?
About Dr Connie Lee Batlevi

Connie Lee Batlevi, MD, PhD, is a Medical Oncologist at Memorial Sloan Kettering Cancer Centre in New York, USA. She received her medical degree from the University of Massachusetts Medical School and completed an Internal Medicine residency at Mount Sinai Hospital/Mount Sinai School of Medicine. She completed her fellowship in hematology/oncology at Memorial Sloan Kettering Cancer Center. She has board certification in internal medicine and oncology.read more

At Memorial Sloan Kettering Cancer Centre, Dr Batlevi treats lymphoma via a variety of techniques, including chemotherapy, immunotherapy, targeted therapy, radiotherapy and stem cell transplantation. She also conducts lymphoma research as part of a team of world-class lymphoma experts who have more than 100 years of combined experience and a shared goal of providing the most effective, personalized care for people with the disease. Dr Batlevi’s research focuses on lymphoma genetics, mechanism-based therapies for targeted therapy, and the application of CAR T cells in the treatment of lymphoma, and she is currently involved in a number of clinical trials investigating immunotherapy, new drug combinations, and biomarker-based targeted therapies.

Dr Connie Lee Batlevi discloses: Research funding from Bayer, Epizyme, Janssen, Novartis and Xynomic Pharmaceuticals. Consulting and advisory board fees from Juno Therapeutics/Celgene, Kite, LifeSci Capital, LLC and Seattle Genetics. Honorarium from Dava Oncology.

 
Dr Laurie Sehn
University of British Columbia, Vancouver, BC, Canada
What is the latest clinical evidence for EZH2 and PI3K inhibitors in patients with R/R FL and how can we translate it into clinical practice?

Dr Sehn explains the latest clinical data for EZH2 and PI3K inhibitors in patients with R/R FL and describes its potential implications for daily clinical practice

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Interview Questions

In this interview, Dr Sehn answers the following questions:

  • What is the latest clinical evidence for use of the EZH2 inhibitor tazemetostat in patients with R/R FL?
  • What do the long-term follow-up data from the CHRONOS-1 study tell us about use of the PI3K inhibitor copanlisib in patients with R/R FL?
  • In the recent DYNAMO study, what were the efficacy and safety results for the PI3K inhibitor duvelisib in the R/R FL patient subset?
  • What is the ZEUS study and what value might its results have for patients with refractory FL treated with the PI3K inhibitor idelalisib?
  • What are the practical implications of the efficacy and safety data for EZH2 and PI3K inhibitors in patients with R/R FL?
About Dr Laurie Sehn

Laurie Sehn is currently Clinical Professor with BC Cancer and University of British Columbia, Canada. She has been a medical oncologist and clinical investigator at BC Cancer since 1998, and is currently the Chair of the Lymphoma Tumour Group. Dr Sehn graduated from McGill Medical School, Montreal, Canada and received her training in Internal Medicine at Columbia Presbyterian Medical Center, Columbia University, New York, USA.read more

She was trained in hematology–oncology at the Dana-Farber Cancer Institute and Brigham and Women’s Hospital, Harvard University, Boston, and received a Masters of Public Health degree from Harvard School of Public Health, Harvard University. Prior to returning to Canada, she spent a year at the Dana-Farber Cancer Institute with the Bone Marrow Transplant service.

Dr Sehn is Chair of the medical advisory board for the International Lymphoma Coalition. She has also served as a member of the Editorial Board of Journal of Clinical Oncology and Leukemia Lymphoma, and is currently an Associate Editor for Blood. Dr Sehn also serves as Co-Chair of the Lymphoma Site of the Canadian Cancer Trials Group.

Dr Laurie Sehn discloses: Consulting fees and honoraria from AbbVie, Acerta, Amgen, Apobiologix, AstraZeneca, Celgene, Gilead, Incyte, Janssen, Karyopharm, Kite, Lundbeck, Merck, Morphosys, Roche/Genentech, Sandoz, Seattle Genetics, Takeda, Teva, TG Therapeutics and Verastem
Research funding from Teva.

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Overview & Learning Objectives
Overview

In this activity, leading lymphoma specialists provide updates on the different prognostic indices and factors and novel treatment strategies, such as PI3K and EZH2 inhibition, for patients with relapsed/refractory follicular lymphoma.

This activity has been jointly provided by Oakstone and touchIME ONCOLOGY. Oakstone Publishing is accredited by the ACCME to provide continuing medical education to physicians. read more

Target Audience

This activity has been designed to meet the educational needs of hematologists and oncologists involved in the management of follicular lymphoma.

Disclosures

Oakstone Publishing has assessed conflict of interest with its faculty, authors, editors, and any individuals who were in a position to control the content of this CME activity. Any identified relevant conflicts of interest were resolved for fair balance and scientific objectivity of studies utilized in this activity. Oakstone Publishing’s planners, content reviewers, and editorial staff disclose no relevant commercial interests.

Content Reviewer

Walter Murray Yarbrough, MD, FACP has no financial interests/relationships or affiliations in relation to this activity.

Touch Medical Director

Sola Neunie has no financial interests/relationships or affiliations in relation to this activity.

Requirements for Successful Completion

This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of Oakstone Publishing and touchIME. Oakstone Publishing is accredited by the ACCME to provide continuing medical education for physicians.

The European Union of Medical Specialists (UEMS) – European Accreditation Council for Continuing Medical Education (EACCME) has an agreement of mutual recognition of continuing medical education (CME) credit with the American Medical Association (AMA). European physicians interested in converting AMA PRA Category 1 Credit™ into European CME credit (ECMEC) should contact the UEMS (www.uems.eu).

Oakstone Publishing designates this enduring material for a maximum of 0.5 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

In order to receive credit for this activity, participants must review and complete the post-test and evaluation form. Statements of credit are awarded upon successful completion of the post-test and evaluation form.

Date of original release: 29 March 2021. Date credits expire: 29 March 2022.

Learning Objectives

After watching this activity, participants should be better able to:

  • Evaluate the key prognostic factors that indicate high risk of inferior outcomes in patients with FL
  • Evaluate novel and emerging treatment strategies for patients with R/R FL
  • Translate the latest clinical data for EZH2 and PI3K inhibitors in patients with R/R FL into clinical practice
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Question 1/4
Your 65-year-old female patient with follicular lymphoma has relapsed within 14 months of treatment with first-line R-CHOP therapy. Her current FLIPI score is 3. What is your prognosis for this patient based on her POD24 status?

FLIPI, Follicular Lymphoma International Prognostic Index; POD24, progression of disease within 2 years; R-CHOP, rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone.
Correct

In an analysis of data from the National LymphoCare Study to identify whether prognostic follicular lymphoma factors are associated with early POD and whether patients with early POD are at high risk for death, 588 patients with stage II–IV follicular lymphoma received first-line R-CHOP therapy. Two groups were defined: patients with early POD ≤2 years after diagnosis and those without POD within 2 years (reference group). Overall survival from a risk-defining event at 2 years in the early-POD group was 68%, and at 5 years it was 50% compared with 97% and 90%, respectively, for patients without early POD.

POD, progression of disease; R-CHOP, rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone.

References

Casulo C, et al. J Clin Oncol. 2015;33:2516–22.

Question 2/4
Based on data from trials of CAR T-cell therapies axicabtagene ciloleucel, tisagenlecleucel and lisocabtagene in patients with R/R follicular lymphoma, what overall response rates might be expected with these therapies?

CAR, chimeric antigen receptor; R/R, relapsed or refractory.
Correct

In the Zuma-5 trial, which is assessing axicabtagene ciloleucel in patients with R/R indolent NHL, in patients with follicular lymphoma (n=84), the ORR was 94%.1 In the Elara trial, which is assessing the efficacy and safety of tisagenlecleucel in patients with R/R follicular lymphoma, of the first 52 patients evaluable for efficacy, the ORR was 83% in the intent-to-treat population.2 Similarly, in the TRANSCEND NHL 001 study, which assessed the efficacy and safety of lisocabtagene maraleucel for patients with R/R large B-cell lymphomas, of 256 patients included in the efficacy-evaluable set, the ORR was 73%.3

AutoHSCT, autologous hematopoietic stem cell transplant; mAb, monoclonal antibody; NHL, non-Hodgkin lymphoma; ORR, overall response rate; R/R, relapsed or refractory.

References
1. Jacobson C, et al. Blood. 2020;136(Suppl 1):40–1.
2. Fowler NH, et al. Blood. 2020;136(Suppl 1):Abstract 1–3.
3. Abramson JS, et al. Lancet. 2020;396:839–52.

Question 3/4
Your 62-year-old female patient was diagnosed with R/R follicular lymphoma 4.5 years ago. She has an ECOG PS of 1, grade 3a histology and recently relapsed on her third line of anticancer therapy. She is refractory to rituximab-containing regimens, has the EZH2 mutation and has uncontrolled type 2 diabetes. Which of these fourth-line treatment options would you most likely consider next?

ECOG PS, Eastern Cooperative Oncology Group performance status; EZH2, enhancer of zeste homolog 2; R/R, relapsed or refractory.
Correct

The FDA has approved tazemetostat for the treatment of patients with R/R follicular lymphoma whose tumors are EZH2-positive as detected by an FDA-approved test and who have received ≥2 prior systemic therapies, as well as those with R/R disease who have no other available satisfactory treatment options.1 The decision was based on data from two open-label, single-arm cohorts (cohort 4, EZH2-mutated [EZH2mut] follicular lymphoma and cohort 5, EZH2 wild-type [EZH2WT] follicular lymphoma) in a phase II study. At a median follow-up of 22.0 months in the EZH2mut cohort and 35.9 months in the EZH2WT cohort, the ORR was 69% in the EZH2mut cohort and 35% in the EZH2WT cohort. Median PFS was 13.8 months and 11.1 months, respectively.2
Copanlisib is approved for patients with relapsed follicular lymphoma who have received ≥2 prior systemic therapies. Patients with diabetes should only be treated with copanlisib following adequate glucose control and should be monitored closely.3

EZH2, enhancer of zeste homolog 2; FDA, US Food and Drug Administration; mut, mutant; ORR, objective response rate; PFS, progression-free survival; R/R, relapsed or refractory; WT, wild type.

References
1. US Food and Drug Administration. Press release. 2020. Available at: www.onclive.com/view/fda-approves-tazemetostat-in-relapsed-refractory-follicular-lymphoma (accessed 03 March 2021).
2. Morschhauser F, et al. Lancet Oncol. 2020;21:1433–42.
3. Aliqopa Prescribing Information, 2017. Available at: www.accessdata.fda.gov/drugsatfda_docs/label/2017/209936s000lbl.pdf (accessed 03 March 2021).

Question 4/4
You are about to initiate idelalisib therapy in your patient with follicular lymphoma who has progressed after four prior regimens. Your patient asks what side effects might be expected with idelalisib. Which of these statements might you include in your advice?
Correct

In interim results from the large non-interventional ZEUS study, which is assessing the real-world safety of idelalisib monotherapy in patients with refractory follicular lymphoma, the most common adverse events of any grade were diarrhea (27%), fever (10%) and cough (9%).1 Similarly, in the earlier phase II clinical trial of idelalisib in patients with relapsed indolent lymphoma, the most common adverse events of any grade were diarrhea (43%), fatigue (30%), nausea (30%) and cough (29%). Of these, only a minority were of grade 3 or above.2

References
1. Salles G, et al. Blood. 2020;136(Suppl 1):Abstract 1145.
2. Gopal AK, et al. N Engl J Med. 2014;370:1008–18.

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