Preface – ASCO/EHA/ICML 2021
Véronique Leblond, MD
Department of Hematology,
Pitié Salpêtrière Hospital
Paris, France
Dear Colleagues,
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.
This publication summarizes studies investigating targeted and immune-directed treatment of B-cell malignancies that were presented at the European Hematology Association (EHA) Annual Congress, 9th–17th June, the 16th International Conference on Malignant Lymphoma (ICML), 18th–22nd June, and the 2021 Annual Meeting of the American Society of Clinical Oncology (ASCO), 4th–8th June 2021.
Chemotherapy-free regimens that can induce deep responses to the point of undetectability of minimal residual disease are generally gaining momentum and have already been established as cornerstones of treatment in various settings. A broad range of clinical trials is exploring effective and tolerable combinations with and without chemotherapeutic agents, as well as potent targeted drugs that show effectivity as monotherapies. BTK inhibition represents an important pillar in the management of diseases such as chronic lymphocytic leukemia, Waldenström’s macroglobulinemia, and marginal zone lymphoma. Trial results have demonstrated that patient outcomes can be improved with the use of newer-generation agents, while yet newer BTK inhibitors are being developed. Likewise, novel BCL2- and PI3K-targeted agents are being designed with optimized features such as increased selectivity. Novel bispecific antibodies appear to offer substantial activity across a range of hematologic entities.
Moreover, the use of drugs that enhance anti-tumor immunity is an attractive approach, both in the single-agent and combination therapy settings. Checkpoint inhibition has been tested successfully in patients with non-Hodgkin lymphoma and classical Hodgkin lymphoma. As for solid tumors, durable responses are being observed in a certain percentage of patients. The development of innovative checkpoint inhibitors, which are expected to provide improved outcomes, is ongoing.
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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.
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.
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.
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.
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.
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.
