New BSH Guidance on Bispecific Antibodies in Lymphoma: What You Need to Know for Your Exams

Bispecific antibodies (BsAbs) are changing the game for relapsed/refractory (R/R) B-cell lymphomas, and this Good Practice Paper details how to use them safely and effectively. Let's dive into the details you need to know. You may have to write an essay question related to this topic.

Reference: https://onlinelibrary.wiley.com/doi/10.1111/bjh.70018

A Head-to-Head Comparison

Four anti-CD3 x CD20 BsAbs are making waves: epcoritamab, glofitamab, mosunetuzumab, and odronextamab. While their efficacy is impressive (Overall Response Rates of 50-80% in heavily pre-treated patients), examiners will want you to know the practical differences between them.

🧠 Exam Tip: An important difference to remember is the route of administration. Epcoritamab is subcutaneous, while the others are IV. This has practical implications for drug delivery and patient convenience that could easily form the basis of a question

Managing the Toxicities

Like CAR-T therapy, the signature toxicities of BsAbs are Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS). However, with BsAbs, these toxicities are generally less frequent, less severe, and more predictable.

Cytokine Release Syndrome (CRS) .This is the most common acute toxicity. You need to know how to spot it, grade it, and manage it.

• Incidence: Occurs in 39-67% of patients, but the vast majority is low grade (Grade 1 or 2). Grade ≥3 CRS is rare (<5%).

• Timing: Highly predictable. It almost always occurs during the step-up dosing in Cycle 1. The peak risk varies by drug:

  • Epcoritamab: After the first full dose (C1D15).

  • Glofitamab: After the first actual glofitamab dose (C1D8).

The Good Practice Paper highlights how to manage this in detail.

Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)

ICANS is much less common and less severe with BsAbs than with CAR-T.

• Incidence: Any grade ICANS is reported in <10% of patients, with most events being Grade 1 and self-limiting.

• Assessment: If suspected, perform a thorough neurological exam and calculate an ICE score (Immune effector Cell-associated Encephalopathy).

🧠 Exam Tip: For any exam scenario involving a patient on a BsAb who develops a fever or confusion, your first steps should be to grade the toxicity using ASTCT criteria, perform a septic screen, and initiate management based on the grade. Knowing the role and timing of tocilizumab is essential.

Beyond Immune Related Adverse Effects: Other Key Side Effects

Don't forget these other important toxicities:

• Infections: Profound B-cell aplasia leads to hypogammaglobulinaemia and a high risk of infection.

  • Prophylaxis: VZV and PJP prophylaxis are mandatory throughout treatment.

  • Monitoring: Check serum immunoglobulin levels.

  • Treatment: Consider IVIG replacement if IgG is <4 g/L in a patient with recurrent/severe infections.

• Cytopenias: Grade 3-4 neutropenia occurs in ~20-30% of patients. This usually responds well to G-CSF.

• Tumour Flare Reaction (TFR): A transient increase in tumour size, sometimes with pain. It's important not to mistake this for early disease progression on imaging.

This new BSH paper is a fantastic revision tool. It clearly outlines the practical, day-to-day management of a therapy class that is here to stay. Ready to test your knowledge? Head over to the AceHaematology question bank and tackle our latest questions on lymphoma, immunotherapy, and managing treatment toxicities.