Canadian Hematology Today

Relapsed or Refractory Mantle Cell Lymphoma: Available and Emerging Therapies

Jean-Nicolas Champagne — 2024-12-03

Mantle cell lymphoma (MCL) is a mature B-cell non-Hodgkin lymphoma (NHL) that accounts for 5–7% of all NHL. In most cases, it is characterized by t(11;14) leading to cyclin D1 overexpression. MCL displays a heterogeneous clinical behavior, ranging from a very indolent to a very aggressive clinical course. Biological features associated with aggressive disease include morphology (pleomorphic or blastoid), high proliferation index (Ki67 >30%), adverse clinical scores (Mantle Cell Lymphoma International Prognostic Index [MIPIb])³, and TP53 mutation status. Patients who relapse within 24 months of initial treatment (POD24) have a poor prognosis with median overall survival (OS) of approximately 12 months.

Most patients achieve long-term disease control with first-line treatment, which currently involves induction rituximab-containing chemotherapy with or without autologous stem cell transplantation, followed by maintenance rituximab. Trials assessing Bruton tyrosine kinase inhibitors (BTKi) and other novel agents in the first-line setting have been recently published or are ongoing. These options are currently not available in Canada outside of clinical trials but may become standard of care in the future.

Relapse after first-line therapy is inevitable, and curability outside the context of allogeneic stem cell transplant (alloSCT) remains unclear, with most patients eventually requiring second and subsequent lines of therapy. In the last decade, new therapies have changed the treatment landscape of relapsed/refractory (R/R) MCL, and their optimal sequencing or combination remain unclear. Treatment options will be described herein, with a proposed treatment algorithm for R/R MCL (Figure 1).

Treatment of Philadelphia Chromosome-negative Myeloproliferative Neoplasms in 2024: A Concise Review

Akhil Rajendra — 2024-12-03

In 1951, William Dameshek coined the term myeloproliferative disorders (MPDs) for diseases characterized by abnormal proliferation of one or more terminally differentiated myeloid cell lines in the peripheral blood.^1,2 In 2008, the World Health Organization (WHO) renamed these disorders as myeloproliferative neoplasms (MPNs) in recognition of their clonal nature. There are currently two classification system for MPNs: WHO and International Consensus Classification (ICC), 2022.^3,4 This review will focus on the Philadelphia chromosome-negative MPNs, which include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF).

Front-line Treatment of Older Patients with Hodgkin Lymphoma

Kelly Davison — 2024-12-03

The evolution of treatment for classical Hodgkin lymphoma (cHL) represents a great success in oncology, with disease outcomes evolving from universally fatal to vastly curable. However, not all patients benefit equally from modern therapies, which include response‑adapted regimens and the addition of novel, targeted agents to the front-line setting. Although patients older than 60 years account for the later peak in cHL’s characteristic bimodal age distribution and represent approximately 20–25% of all patients with cHL, their outcomes remain inferior compared to younger patients. A retrospective study including 401 patients >60 years treated in British Columbia between 2000 and 2019 revealed modest progression‑free survival (PFS) and disease-specific survival rates of 50% and 63%, respectively, with a median follow-up of nine years. While these outcomes have improved relative to cohorts treated prior to 2000, they nevertheless fall short of those experienced by younger patients. Furthermore, the gap in outcomes between young and older patients progressively worsens with each increasing age decile, with patients >70 years having a particularly poor prognosis. This shortfall has been attributed in part to patient-specific factors such as comorbidities and frailty, which may limit treatment tolerance, but also to differing disease biology, with negative prognostic features including advanced stage disease, Epstein-Barr virus positivity, and mixed cellularity histology often present in those with older age. Adding to the challenges in treating older patients is the fact that this group is frequently underrepresented in clinical trials, or excluded altogether, making their optimal treatment ill-defined.

The Evolving Landscape of DLBCL Treatment Beyond the First Line in 2024

Mark Bosch — 2024-12-03

The landscape for treating relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) in 2024 is rapidly evolving, with various treatment options emerging. Traditionally, salvage chemotherapy followed by autologous stem cell transplant (ASCT) has been the primary treatment for young, fit patients with R/R DLBCL, and only limited options exist for those ineligible for transplant. However, recent research and regulatory approvals, such as chimeric antigen receptor (CAR) T-cell and bispecific antibody therapies, have significantly improved our ability to treat patients previously considered palliative for R/R DLBCL.

Moreover, further research has demonstrated that these advanced technologies are not only effective in the transplant setting but also in individuals who are not traditionally eligible for ASCT and those with comorbid conditions. One anticipated development has been the provincial approvals of bispecific T-cell engagers (BiTEs), such as epcoritamab and glofitamab, which target CD20 and CD3. BiTE therapy holds promise as an off-the-shelf treatment option, potentially offering wider availability to patients compared to CAR T-celll therapy or even post‑CAR T-cell failure.

Minimal Residual Disease in Myeloma in 2024: Where We are Today

Alfredo De la Torre — 2024-12-03

Minimal residual disease (MRD) refers to a small population of cancer cells that persists in the body after treatment. Often undetectable using traditional diagnostic methods, these cells can eventually cause relapse in patients who appear to have achieved a complete response (CR) to treatment. For that reason, MRD has become a vital parameter in evaluating the effectiveness of cancer therapies, particularly in hematological malignancies, such as multiple myeloma (MM), and certain solid tumours.

Detection of MRD represents a challenge, as the disease may not cause symptoms or be detected through traditional methods (i.e., visible under a microscope). Nevertheless, these cells are often responsible for disease relapse; alternatively, sustained absence of these cells may portend a prolonged remission and presumably be required for disease cure. Therefore, monitoring and detecting MRD are increasingly recognized as essential for long-term patient care and treatment planning.