The use of ibrutinib before and after allogeneic stem cell transplantation

ABSTRACT

Background: FDA designated ibrutinib as a breakthrough therapy in Mantle Cell Lymphoma (MCL) and Chronic Lymphocytic Leukemia (CLL). Nevertheless, patients who progress under ibrutinib still have a poor prognosis. In this setting, allogeneic hematopoietic stem cell transplantation (allo-HSCT) could induce long-term disease control.

Areas covered: The purpose of the present review is to provide information on the efficacy of ibrutinib when administered before and after allo-HSCT for CLL and MCL. Moreover, we will focus on the current role of ibrutinib for chronic GVHD.

Expert opinion: Ibrutinib as bridge to allo-HSCT does not appear to affect the safety of the treatment in patients with CLL and MCL. Current evidence support further evaluation of ibrutinib for the treatment of relapsed CLL and MCL after allo-HSCT. In this setting, ibrutinib should be not only highly efficient on CLL and MCL cells but might also have the ability to enhance the activity of donor T cells. Chronic GVHD is the most common long-term complication following allo-HSCT. Results from a phase 2 clinical trial culminated in the FDA-approval of ibrutinib as second-line therapy of steroid-refractory or steroid-resistant chronic GVHD. A randomized, controlled trial in patients with chronic GVHD should be performed.

KEYWORDS:

• Ibrutinib
• chronic GVHD
• allogeneic hematopoietic stem cell transplantation
• chronic lymphocytic leukemia
• mantle cell lymphoma

Article highlights

• Ibrutinib is a novel, orally active, irreversible inhibitor of Bruton’s tyrosine kinase (BTK) that has demonstrated considerable efficacy in a variety of B-cell malignancies

• The US Food and Drug Administration (FDA) designated ibrutinib as a breakthrough therapy and treatment options for patients with Chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL)

• Ibrutinib is not a curative treatment in these indications, and who progress under ibrutinib still have a poor prognosis

• Allogeneic hematopoietic stem cell transplantation (allo-HSCT) could induce long-term disease control with therapeutic potential in poor prognosis and select fit patients

• Ibrutinib for bridging to allo-HSCT does not appear to adversely affect engraftment, Graft Versus Host Disease (GVHD) risk, and non-relapse mortality

• Ibrutinib induced a high rate of sustained responses for patients with chronic GVHD and inadequate response to corticosteroid-containing therapy.

• Results from a phase 2 clinical trial culminated in the FDA-approval of ibrutinib as second-line therapy of steroid-refractory or steroid-resistant chronic GVHD

• Ibrutinib can be safely administered for CLL/MCL relapse after allo-HSCT, with efficacy at least similar to non-transplanted patients with high-risk disease.

This box summarizes the key points contained in the article.

Declaration of interest

No potential conflict of interest was reported by the authors.