CAR-T cell therapy has significantly improved outcomes for patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), but challenges such as limited resources, manufacturing timelines, and notable toxicities persist. Bispecific antibodies (BsAbs), including glofitamab and epcoritamab, have demonstrated promising efficacy and represent a new treatment option in patients who are unsuitable for or have relapsed following CAR-T therapy. Bispecific antibodies have a manageable safety profile and are generally more widely accessible than CAR-T cell therapy. Case discussions in this paper illustrate the potential real-world application of BsAbs, highlighting their role in treating patients who have relapsed after or are unable to undergo CAR-T cell therapy. Overall, glofitamab and epcoritamab represent valuable treatment options in the evolving landscape of R/R DLBCL.

Primary central nervous system lymphoma (PCNSL) is a rare malignancy. Standard of care is upfront high-dose methotrexate (HD-MTX) chemotherapy, while cranial radiation is more commonly used in the salvage setting. In this retrospective study, we aimed to investigate the safety and efficacy of salvage cranial radiation in PCNSL. PCNSL patients who received upfront HD-MTX chemotherapy and salvage cranial radiation after treatment failure between 1995 and 2018 were selected. Radiological response to cranial radiation was assessed as per Response Assessment in Neuro-Oncology Criteria. Twenty one patients were selected (median age 59.9 years), with median follow-up of 19.9 months. Fourteen patients (66.7%) received a boost to the gross tumour volume (GTV). Four patients (19.0%) sustained grade ≥2 treatment-related neurotoxicity post-completion of cranial radiation. Of the 19 patients who had requisite MRI with gadolinium imaging available for Response Assessment in Neuro-Oncology (RANO) criteria assessment, 47.4% achieved complete response, 47.4% achieved partial response, and 5.3% of patients exhibited stable disease. Higher dose to the whole brain (>30 Gy) was associated with higher rate of complete response (63.6%) than lower dose (≤30 Gy, 37.5%), while boost dose to the gross disease was also associated with higher rate of complete response (61.5%) compared with no boost dose (33.3%). Median overall survival was 20.0 months. PCNSL patients who relapsed following upfront chemotherapy showed a high rate of response to salvage cranial radiation, especially in those receiving greater than 30 Gy to the whole brain and boost to gross disease.

CAR-T cell therapy has significantly improved outcomes for patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), but challenges such as limited resources, manufacturing timelines, and notable toxicities persist. Bispecific antibodies (BsAbs), including glofitamab and epcoritamab have demonstrated promising efficacy and represent a new treatment option in patients who are unsuitable for or have relapsed following CAR-T therapy. Bispecific antibodies have a manageable safety profile and are generally more widely accessible than CAR T-cell therapy. Case discussions in this paper illustrate the potential real-world application of BsAbs, highlighting their role in treating patients who have relapsed after or are unable to undergo CAR T-cell therapy. Overall, glofitamab and epcoritamab represent valuable treatment options in the evolving landscape of R/R DLBCL.

(1) Background: Bispecific antibodies (BsAbs) for the treatment of relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) can be delivered in ambulatory healthcare settings; however, the safe and effective management of potential side effects, such as cytokine release syndrome (CRS), requires protocolized monitoring and management. (2) Methods: An Expert Working Group (EWG) of nine hematologists from across Canada, with experience in leading BsAb program implementation, combined a review of published literature, a comparison of national/provincial/regional guidance documents and protocols, and their professional experiences to produce an informed framework for BsAb program implementation in various healthcare settings. (3) Results: The EWG supports and recommends the progression of BsAb provision from predominantly inpatient hospital settings to community/ambulatory care settings closer to the patient’s home. A seven-step implementation process is outlined to support the safe and effective establishment of such programs, from establishing leadership, through customization of protocols, to education and execution. Strategies and considerations are offered to overcome potential barriers and empower healthcare professionals who are working to establish or improve BsAb programs across Canada. (4) Conclusions: For patients with R/R DLBCL, the safe and effective provision of BsAbs closer to home is both feasible and preferred. This guidance is intended to support the efficient and effective setup or enhancement of BsAb programs in lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma and remains curable for many patients with frontline immunochemotherapy; however, optimal treatment continues to evolve. The Canadian Hematology Consensus Group convened a national panel of lymphoma experts to develop evidence-informed recommendations for the first-line management of adults with DLBCL in Canada. Recommendations were developed using a modified Delphi process and address frontline regimen selection, treatment intensity, central nervous system (CNS) risk assessment and prophylaxis, interim response assessment, and end of treatment management. The panel recommends Pola-R-CHP for patients with international prognostic index 2–5 and activated B-cell subtype by gene expression profiling (or if unavailable, non-germinal centre B-cell subtype by immunohistochemistry). All patients should be assessed for fitness to receive full-dose therapy, with dose attenuation considered when clinically appropriate. Routine high-dose methotrexate prophylaxis is not recommended, and CNS screening should be individualized. Interim imaging may be used to confirm response, but treatment escalation should not be based on PET positivity alone. Patients achieving complete metabolic response at end of treatment require no further therapy, and routine surveillance imaging is not recommended. These recommendations support consistent, evidence-informed, and equitable care for patients with newly diagnosed DLBCL across Canada.

Maintenance rituximab (MR) has been a mainstay of treatment in Canada for CD20‑positive indolent lymphoma for two decades. The adoption of MR into clinical practice occurred after the publication of the EORTC 20981 trial. This trial showed a significant improvement in progression free survival (PFS) with two years of MR versus observation after induction therapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with relapsed follicular lymphoma (FL). The use of MR was broadly extended to include its use in the front‑line setting, following any R-containing inductions and including all CD20-positive indolent lymphoma histologies. Automatic recommendations for MR became the standard practice for most patients. Given the recent changes to standard induction regimens in some indications, and with heightened concerns about infectious complications during B-cell depleting therapy, the recommendation for the use of MR should no longer be considered automatic. This review offers a balanced perspective of the evidence for MR.