ASCO/EHA/ICML 2021
Lecture Board: Othman Al-Sawaf, MD; Stephen M. Ansell, MD; PhD Jorge Castillo, MD; Chan Cheah, MBBS; Jeff Sharman, MD
Medical Writer: Judith Moser, MD
Publishing Editor: Anna Fenzl, PhD
Preface – ASCO/EHA/ICML 2021
As virtual scientific conferences are becoming part of our daily routine as clinicians and researchers, information in individual areas of interest is easily accessible across different congresses.
CLL/SLL: current perspectives across a range of potent agents
The introduction of effective inhibitors of B-cell receptor signaling such as the BTK inhibitor ibrutinib has transformed the treatment of patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). The irreversible, potent, next-generation BTK inhibitor zanubrutinib has been designed to maximize BTK occupancy and minimize off-target inhibition of other kinases.
Waldenström’s macroglobulinemia: outcome optimization via combinations
Ibrutinib is the only once-daily BTK inhibitor approved as a single agent or in combination with rituximab for patients with Waldenström’s macroglobulinemia (WM) across all lines of therapy. In the international, double-blind, randomized, phase III iNNOVATE trial, ibrutinib plus rituximab was tested against placebo plus rituximab in patients with rituximab-sensitive WM.
Successful inhibition of PI3K, BTK, BCL2 and other targets in various B-cell malignancies
Rituximab monotherapy is a recognized standard of care in patients with relapsed indolent non-Hodgkin lymphoma (iNHL) who have had long remissions after rituximab-based therapy or who are unwilling or unfit to be treated with chemotherapy. However, the clinical benefit conferred by rituximab can be limited due to drug resistance.
Extending anti-PD-1–based options in the setting of Hodgkin lymphoma
Patients with relapsed or refractory classical Hodgkin lymphoma (cHL) who have failed high-dose chemotherapy and autologous stem cell transplantation (HDT/ASCT) have poor prognosis, which also applies to those with chemotherapy-resistant disease who are ineligible for HDT/ASCT. The presence of chromosome 9p24.1 alterations in cHL provides a rationale for immune checkpoint inhibition as this leads to overexpression of the PD-L1 ligands.
Mantle cell lymphoma: improving outcomes in difficult-to-treat patient populations
Mantle cell lymphoma (MCL) accounts for approximately 3–10 % of non-Hodgkin lymphomas and shows one of the poorest survival rates among the lymphomas. The combination of lenalidomide and rituximab (R2) has demonstrated activity in MCL patients in the frontline and relapsed/refractory settings, with overall response rates (ORRs) of 92 % and 57 %, respectively.
Zanubrutinib in relapsed/refractory marginal zone lymphoma: MAGNOLIA
B-cell receptor-mediated signaling has been identified as a critical step in marginal zone lymphoma (MZL) pathogenesis. Accordingly, BTK inhibition is effective in the management of patients with relapsed/refractory MZL, as shown for the first-generation BTK inhibitor ibrutinib. The multicenter, single-arm, phase II MAGNOLIA study is evaluating the next-generation BTK inhibitor zanubrutinib 160 mg twice daily in patients with relapsed/refractory MZL including splenic, nodal and extra-nodal subtypes after pretreatment with ≥ 1 CD20-based regimen.
Novel bispecific antibodies in CD20-positive B-cell non-Hodgkin lymphomas
The T-cell–engaging bispecific antibody glofitamab has been designed with a 2:1 configuration that enables bivalent binding to CD20 on B cells and monovalent binding to CD3 on T cells [1]. Compared to alternative bispecific formats, this offers greater avidity, potency and combinability with other anti-CD20 IgG antibodies.
EXPERT VIDEOS
All video interviews from ASCO/EHA/ICML 2021
Alvaro Alencar discusses which first-line treatment options might soon be established for newly diagnosed patients with mantle cell lymphoma who are not eligible for intensive therapy, what can be expected in terms of innovative approaches in the setting of R/R mantle cell lymphoma or marginal zone lymphoma and highlights the need for robust prognostic tools allowing stratification of treatment modalities.
Matthew Davids depicts the most interesting trial results in the field of CLL treatment at the EHA 2021 congress, gives an outlook on the most promising agents currently tested for use not only in elderly but also in young, fit CLL patients and talks about combinations that might be implemented as pillars of CLL treatment based on current trials.
Wojciech Jurczak gives an overview of the advantages of new BTK inhibitors, the results of the ALPINE trial comparing zanubrutinib with ibrutinib in patients with relapsed/refractory CLL/SLL and talks about which new developments can be expected in the field of innovative BTK inhibitors in the treatment of CLL and other indications.
Carol Moreno highlights the CLL study results from EHA and ICML, enlarges on fixed-duration regimens in CLL treatment, the importance of long-term follow-up findings obtained in important trials such as CLL14 and ELEVATE-TN as well as data from the ALPINE and ELEVATE-RR studies and shares her thoughts on the role of new agents such as zanubrutinib in the overall treatment landscape.
Anthony Mato talks about the study highlights presented at EHA and ICML, innovative treatment approaches currently tested for use in CLL that appear most promising and explains how the prognosis of CLL patients might change due to new therapies in the years to come and summarizes potential strategies to prevent and overcome resistance to targeted therapies.
Christian Buske relates to recent developments with respect to the role of BTK inhibitors and their potential future combination partners in the treatment of patients with Waldenström’s macroglobulinemia, the results of the iNNOVATE study and personalized treatment according to genotypes.
Roger Owen summarizes the status of emerging therapeutic agents for the treatment of patients with Waldenström’s macroglobulinemia, highlights those that appear most promising, even after failing BTK inhibitors, talks about how to guide treatment decisions, the influence of the mutation profile and expectations of BTK inhibitors in patients with relapsed and refractory marginal zone lymphoma.
Like its predecessors conducted onsite, the EHA25 Virtual Congress offered original unpublished scientific hematology data, hematological innovations, and evidence-based knowledge of primary clinical relevance.
This memo inHaematology publication summarizes content presented on the topics of B cell malignancies, paroxysmal nocturnal hemoglobinuria, and cold agglutinin disease.