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Managing BTK Inhibitor Toxicities

CE / CME

Optimizing the Use of BTK Inhibitors in B-Cell Malignancies: Addressing BTK Inhibitor Toxicities

Pharmacists: 1.00 contact hour (0.1 CEUs)

Physicians: Maximum of 1.00 AMA PRA Category 1 Credit™

Nurses: 1.00 Nursing contact hour

Released: September 29, 2021

Expiration: September 28, 2022

Christopher R. Flowers
Christopher R. Flowers, MD, MS
CME/CE Information

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B-Cell Malignancies: Cell Types and Associated Diseases

There are numerous B-cell malignancies, and this slide shows how a selection of these diseases relate to normal B-cell components. Most B-cell malignancies arise from B-cells that have either come through or are in the pregerminal center.

The focus of our discussion today will be MCL, MZL, CLL, and WM, which all can be treated with BTK inhibitors targeting the B-cell receptor pathway.1-4

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BTK Signaling Pathway

Survival of resting mature B-cells is dependent on B-cell receptor (BCR) pathway signaling, with some malignancies depending on what is called “tonic”—ligand independent—BCR signaling and others depending on chronic BCR signaling.5,6 Tonic BCR signaling is necessary for the survival and development of B-cells; chronic BCR signaling supports proliferation of malignant B-cells.7

Blockade of the BCR signaling pathway with BTK inhibitors can lead to apoptosis and inhibit the adhesion of malignant B-cells to microenvironment cells, which also leads to malignant cell death.8

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Indications for Available BTK Inhibitors

The first FDA-approved BTK inhibitor was ibrutinib, which currently has multiple indications.9 Ibrutinib is indicated for adults with MCL who have received ≥1 prior line of therapy; adults with CLL with or without the 17p deletion; adults with WM; and adults with MZL who have received ≥1 prior line of therapy including an anti-CD20–based therapy. Outside of the malignant diseases, ibrutinib also is indicated for adults with chronic graft-vs-host disease who have received ≥1 line of systemic therapy.

The second BTK inhibitor to be approved was acalabrutinib.10 This agent is indicated for adults with MCL who have received ≥1 prior line of therapy and adults with CLL/SLL.

Zanubrutinib is the third FDA-approved BTK inhibitor and is indicated for adults with MCL who have received ≥1 prior therapy, adults with WM, and adults with relapsed/refractory MZL who have received ≥1 prior line of an anti-CD20–based therapy.11

Each drug is under ongoing investigation for other indications.

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