The use of ibrutinib before and after allogeneic stem cell transplantation

Ibrutinib for Chronic Graft-Versus-Host Disease

“…4 Symptoms of GvHD often manifest initially as mouth sores and/or skin rash, 4 and can progress to include dry mouth, gastrointestinal distress, elevated serum bilirubin, fatigue, shortness of breath and/or trouble breathing, and musculoskeletal pain and weakness. 1,7,8 The severity of disease is primarily characterized clinically by the extent of organ involvement (including the skin) and the effects on lung capacity and function. [8][9][10] Patients can experience significantly limited quality of life and negative impacts to their activities of daily life, [11][12][13] with more severe disease associated with less favourable patient experiential outcomes.…”

“…4,6,14 Ibrutinib (brand name Imbruvica) is a Bruton's tyrosine kinase (BTK) inhibitor that received approval from Health Canada and the FDA as second-line treatment for CGvHD in 2017. 4,5,7,14,18 Ibrutinib is prescribed as a once-daily tablet for patients with CGvHD which is administered until treatment is no longer required (i.e., CGvHD has resolved) or in the event that toxicity becomes intolerable. 4 Ibrutinib can cause side effects including cardiovascular conditions (e.g., arrhythmias, atrial fibrillation, and heart failure), central nervous system effects (e.g., fatigue, weakness), gastrointestinal toxicity (e.g., nausea, diarrhea), hematologic conditions (e.g., thrombocytopenia and anemia), dermatologic conditions, as well as pneumonia (among others).…”

“…23 However, this study was limited by its open-label, non-randomized design and small sample size. 5,7 Because of the early data indicating that ibrutinib can be an effective intervention for treatment-refractory CGvHD, as well as the relatively recent Health Canada approval of its use for CGvHD, a review of the most current comparative evidence is needed to inform health care and policy decisions that will optimally benefit patients. Consequently, this report aims to synthesize and assess currently available comparative evidence describing the clinical effectiveness of ibrutinib for the treatment of patients with CGvHD who have experienced inadequate response to corticosteroids or other systemic therapies.…”

“…Currently available evidence describing ibrutinib for treatment-refractory CGvHD was not eligible for this review (i.e., the studies published to date use single-arm, non-randomized, non-comparative designs that cannot offer robust insight into comparative clinical effectiveness). 7,15 Specifically, single-arm trials lack the comparison group(s) necessary to provide a frame of reference that can establish whether observed effect(s) were due to the intervention under study or some other factor(s). 24 Comparative randomized controlled trials are needed to inform clinical and health care decisions concerning the use of ibrutinib for treatment-refractory CGvHD.…”

“…Studies examining the effect of ibrutinib for the treatment of CGvHD in a first-line setting have been characterized as critical to understanding its optimal use for these patients. 7 One randomized controlled trial is currently under way examining the effect of ibrutinib as a first-line therapy for the treatment of CGvHD 31 and other single-arm trials are investigating the effects of ibrutinib as either first-line or second-line treatment as monotherapy or in parallel with other drugs (e.g., corticosteroids or rituximab). 32 Other non-comparative research is focused on minimizing the side effects and adverse events caused by ibrutinib while treating various conditions (including CGvHD), such as fungal infections.…”