Canadian Hematology Today

New Developments in the Front‑line Treatment of Advanced Stage Classic Hodgkin Lymphoma: A Canadian Perspective

2025-12-08T19:09:59+00:00

Classic Hodgkin lymphoma (cHL) is highly curable, with excellent outcomes achieved through decades of treatment refinement. Recent years have witnessed a paradigm shift in the management of patients with advanced stage disease, driven by the integration of novel therapies into front-line treatment. Minimizing long-term complications remains an important objective, especially for patients in the adolescent/young adult (AYA) age group. Herein, we summarize the latest developments in the treatment of advanced stage cHL through a Canadian lens, focusing on recent clinical trials that have reshaped the therapeutic landscape.

Practical Management of Aggressive B-Cell Lymphomas with CD20×CD3 Bispecific Antibodies

2025-12-08T19:09:58+00:00

CD20×CD3 bispecific antibodies (BsAbs) have transformed the therapeutic landscape of relapsed or refractory large B-cell lymphoma (LBCL). By redirecting T cells to target CD20-expressing lymphoma cells, these off-the-shelf agents offer high response rates and durable remissions in patients who previously had limited options, including those who relapse after chimeric antigen receptor T-cell therapy. In Canada, epcoritamab and glofitamab are now approved for patients with LBCL after at least two prior lines of treatment. The combination of glofitamab, gemcitabine, and oxaliplatin has been recently approved for patients with relapsed/refractory diffuse large B-cell lymphoma not otherwise specified LBCL after at least 1 line of therapy and who are ineligible for autologous hematopoietic stem cell transplant. This review provides a practical framework for Canadian hematologists: identifying eligible patients, implementing pretreatment evaluation, safely delivering therapy in inpatient and outpatient settings, and managing toxicities such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. We will also discuss infection prophylaxis, sequencing with cellular therapies, and future directions for BsAbs in earlier treatment lines.

Unique Toxicities of Novel Myeloma Therapies: Focus on Belantamab Mafodotin, Talquetamab, and Selinexor

2025-12-08T19:09:57+00:00

Recent survival improvements in patients with multiple myeloma are attributable largely to the introduction of three main drug classes, immunomodulatory drugs (IMIDs), proteasome inhibitors, and anti-CD38 monoclonal antibodies. However, the majority of patients will inevitably develop resistance to all three drug classes, and survival in this setting has been historically poor.

Several novel therapeutic classes exploiting new mechanisms of action (e.g., chimeric antigen receptor (CAR)-T cell therapy, bispecific antibodies, antibody-drug conjugates (ADC), and selective inhibitors of nuclear export) have shown high levels of activity in relapsed myeloma and promise to transform the treatment landscape. However, these therapies have been associated with distinct toxicity profiles, with adverse effects that are uncommonly observed with conventional antimyeloma therapies. Given improvements in long-term disease control and survival with current therapies, treatment-related toxicity represents an increasingly important health burden in patients with myeloma, and the development of effective toxicity management strategies is required to minimize complications and ensure preserved quality of life.

Rational Use of Immunoglobulin in Adult Patients with Secondary Hypogammaglobulinemia in the Setting of Hematologic Malignancy: A Canadian Perspective

2025-12-08T19:09:56+00:00

Hypogammaglobulinemia is identified by the detection of low serum immunoglobulin (Ig) levels. Secondary hypogammaglobulinemia (SHG) is an acquired state in which circulating Ig levels are reduced due to suppressed antibody production or increased antibody loss. Specifically, SHG most commonly refers to low circulating total IgG levels. In contrast, primary hypogammaglobulinemia (PHG) is due to an underlying inborn error of immunity contributing to low or defective Ig production and frequent and/or severe infections.

In patients with hematologic malignancies, it is important to evaluate baseline Ig (IgG, IgM, IgA) levels at the time of diagnosis. However, it may be challenging to distinguish whether low Ig levels are attributable to PHG or SHG, if antibody defects are identified in the context of hematologic malignancies (including chronic lymphocytic leukemia [CLL], lymphoma, and multiple myeloma), even before initiation of immunosuppressive treatment, PHG should be considered, especially in younger patients presenting with a hematologic malignancy who have a history of recurrent, severe infections.

Treatment of several hematologic malignancies includes anti-CD20 B cell‑depleting therapy, which is known to cause the development of SHG. Advancements in lymphoma and myeloma management now incorporate bispecific antibody therapies and chimeric antigen receptor T-cell (CAR T-cell) therapies, which have revolutionized care for patients with disease refractory to conventional treatments. However, the risk of SHG is significant, with rates of ≥70% with bispecific antibody treatments and 20–46% with CAR T-cell therapies. Thus, patients with hematologic malignancies have a high rate of SHG attributable to both the underlying disease and associated treatment.