Canadian Hematology Today

Cellular Therapy and Follicular Lymphoma: Where Do We Stand in 2025?

Hadel El-Haddad, MD, Hannah Cherniawsky, MD, MSc — Mon, 22 Sep 2025 00:00:00 +0000

Patients with low-risk follicular lymphoma (FL) have a median overall survival (OS) exceeding 20 years. Whereas those with adverse features, such as a high Follicular Lymphoma International Prognostic Index (FLIPI) score or progression of disease within 24 months of front-line treatment (POD24) have inferior outcomes. Standardized treatment in the second line and beyond is not firmly established and largely depends on patient fitness and medication access. The duration of response decreases with each line of therapy. In this review, we evaluate the evidence for T-cell‑redirecting therapies in FL.

Front-line Treatment for Chronic Lymphocytic Leukemia in 2025: Finite Duration Versus Continuous Treatment

Chathuri Abeyakoon, MD, Abi Vijenthira, MD — Mon, 22 Sep 2025 00:00:00 +0000

Chronic lymphocytic leukemia (CLL) is an indolent lymphoproliferative disorder and is the most common hematologic malignancy in Western populations. In Canada, an estimated 2,000 or more new cases are diagnosed each year. Improvements in diagnostic techniques, enhanced prognostication methods, and the development of targeted treatments have revolutionized the management of CLL over the past decade. Despite an ever-expanding therapeutic landscape (Figure 1), the decision to initiate treatment continues to be guided by the International Workshop on CLL criteria.

For patients who require treatment, we now have a choice of two treatment approaches based on current Health Canada approvals: fixed‑duration therapy (e.g., chemoimmunotherapy, venetoclax‑obinutuzumab [VO], or ibrutinib‑venetoclax [IV]) versus continuous treatment until disease progression or toxicity (i.e., Bruton’s tyrosine kinase inhibitors [BTKi]). In this review, we will summarize the evidence for these two approaches and provide our views on factors that may influence treatment selection.

Intensive Versus Non-intensive Therapy for Patients with Newly Diagnosed Acute Myeloid Leukemia (AML)

Karen W.L. Yee, MSc, MD, FRCPC — Mon, 22 Sep 2025 00:00:00 +0000

Newly approved treatments have increased the options available for patients with acute myeloid leukemia (AML), but have also generated questions concerning the selection of the most appropriate therapy for a given individual (Tables 1 & 2). The trials leading to the approval of these therapies were based on limited genetic data (e.g., cytogenetics, FMS-like tyrosine kinase-3 [FLT3] status) and clinical parameters (e.g., age, comorbidities, therapy, or secondary AML). Data concerning effectiveness or lack of efficacy of a drug or drug regimen in specific AML subgroups is often determined after drug approval. For example, venetoclax (VEN) + azacitidine (AZA) lower intensity therapy (LIT), which is approved for the treatment of patients with newly diagnosed AML deemed ineligible for intensive chemotherapy (IC) or aged >75 years, was found to have limited efficacy in patients with mutated TP53. Despite the regulatory approved indications for VEN‑based LIT, some older and younger patients can be selected for either LIT or IC. Furthermore, with the availability of maintenance therapy after IC16, several important questions have emerged regarding the role of IC in older patients.

No published prospective studies have compared IC with LIT in “fit” patients with newly diagnosed AML to inform treatment choice. Two retrospective propensity score matched real‑world data analyses of outcomes in patients with newly diagnosed AML (irrespective of the genetic profile) who received induction with VEN + AZA or IC, indicated no difference in overall survival (OS). However, one study showed improved complete remission (CR) and/or allogeneic hematopoietic stem cell transplant (alloHCT) rates in favour of IC (60.9% vs. 44.2%, P = 0.006 and 18.1% vs. 8.0%, P = 0.012, respectively). Other single‑centre retrospective studies comparing VEN + AZA with IC have yielded conflicting results. None of these studies provided information concerning the use of oral AZA maintenance therapy. The studies did suggest that outcomes may be dependent on specific genetic abnormalities and/or clinical factors. Currently, several Phase 2 trials are comparing VEN + AZA with IC in adult patients with newly diagnosed AML (NCT04801797, NCT05904106, NCT05554406, NCT05554393).

Here, two case scenarios will be discussed to highlight issues surrounding treatment choice: a) fit individuals who are ≥75 years with newly diagnosed European LeukemiaNet (ELN)-defined favourable-risk AML and b) IC eligible persons who are ≥18 years with newly diagnosed ELN‑defined poor-risk AML, who require alloHCT in first complete remission (CR1) with curative intent.

Management of Newly Diagnosed Primary Central Nervous System Lymphoma

Diva Baggio, MD, Chris P. Fox, MBChB, FRCP, FRCPath, PhD — Mon, 22 Sep 2025 00:00:00 +0000

The last decade has witnessed significant progress in the clinical management of patients with newly diagnosed primary central nervous system (CNS) diffuse large B-cell lymphoma (PCNS-DLBCL, hereafter referred to as PCNSL). Data from several clinical trials have demonstrated the potential for long-term remission in a proportion of patients, particularly those eligible for intensive multi-agent chemotherapy approaches. High-dose methotrexate (HD‑MTX)‑based induction regimens remain standard-of-care globally for both younger and older patients with newly diagnosed PCNSL. However, with clinical trial data demonstrating the efficacy of multiple regimens (differing in partner chemotherapy agents, hematological toxicity, and MTX dose density), but with few randomized comparisons, the optimal induction regimen remains unclear.

Consolidation therapy is key to survival outcomes in PCNSL. Thiotepa-based autologous stem cell transplantation (TT-ASCT) has been widely adopted as the consolidation therapy of choice for patients ≤70 years. However, it is increasingly recognized that appropriately selected patients older than 70 years can also benefit from TT-ASCT consolidation. In parallel, declining rates of whole-brain radiotherapy (WBRT) have been observed due to significant risk of neurotoxicity, particularly in patients aged ≥60 years.

This review summarises the contemporary clinical management of patients with newly diagnosed PCNSL. We focus on key diagnostic considerations, the landscape of evidence-based first-line treatments, and practical guidance for treatment selection and delivery. We also briefly discuss specific scenarios, including human immunodeficiency virus (HIV)-associated PCNSL and vitreoretinal involvement in the context of PCNSL.

Concise Review of Chronic Myelomonocytic Leukemia in Canada in 2025

Jacqueline Costello, MD — Mon, 22 Sep 2025 00:00:00 +0000

Chronic myelomonocytic leukemia (CMML) is a clonal myelodysplastic syndrome/myeloproliferative overlap neoplasm characterized by prominent monocytosis, with a very heterogeneous clinical presentation and an inherent risk of transforming to acute myeloid leukemia (AML). It is relatively rare, and the incidence is poorly defined. A Canadian analysis of a period of 20 years identified 1,440 cases and reported an incidence of 2.45 cases per 1,000,000. Given that it often presents at an advanced age, with a median age of 70–76 years, aggressive therapeutic approaches are limited.