Incidence and management of toxicity associated with ibrutinib and idelalisib: a practical approach

Abstract

The use of novel B-cell receptor signaling inhibitors results in high response rates and long progression-free survival in patients with indolent B-cell malignancies, such as chronic lymphocytic leukemia, follicular lymphoma, mantle cell lymphoma and Waldenström macroglobulinemia. Ibrutinib, the first-in-class inhibitor of Bruton tyrosine kinase, and idelalisib, the first-in-class inhibitor of phosphatidylinositol 3-kinase δ, have recently been approved for the treatment of several indolent B-cell malignancies. These drugs are especially being used for previously unmet needs, i.e., for patients with relapsed or refractory disease, high-risk cytogenetic or molecular abnormalities, or with comorbidities. Treatment with ibrutinib and idelalisib is generally well tolerated, even by elderly patients. However, the use of these drugs may come with toxicities that are distinct from the side effects of immunochemotherapy. In this review we discuss the most commonly reported and/or most clinically relevant adverse events associated with these B-cell receptor inhibitors, with special emphasis on recommendations for their management.

Figure 1

Summary of relevant issues relating to bleeding and anticoagulation during ibrutinib treatment.

Figure 2

Flowchart for management of atrial fibrillation during ibrutinib use. ae.g. digoxin ^be.g. verapamil, diltiazem. DOAC: directly acting oral anticoagulants; VKA: vitamin K antagonists.

Figure 3

Flowchart for management idelalisib-induced diarrhea. GI: gastrointestinal tract. IV: intravenous.

Figure 4

Flowchart for management of respiratory complaints during idelalisib use. BAL: broncho-alveolar lavage; HRCT: highresolution computed tomography.

Figure 5

Flowchart for management of transaminitis during idelalisib treatment. AST: aspartate transaminase; ALT: alanine transaminase; ULN: upper limit of normal; BID: bis in die.

Figure 6

Recommendations for the clinic summarizing important toxicity-related issues during therapy with ibrutinib or idelalisib. DOAC: directly acting oral anticoagulants; LMWH: low-molecular-weight heparin; PJP: Pneumocystis jiroveci pneumonia; CMV: cytomegalovirus.