Aplastic anemia triggered by the Bruton tyrosine kinase inhibitor acalabrutinib in two patients with mantle cell lymphoma – a case report

Abstract

The use of Bruton's tyrosine kinase inhibitors (BTKi) is rapidly increasing for patients with mantle cell lymphoma (MCL). Side effects reported so far are usually manageable and self-determining after dose-reduction or termination of the drug. However, here we present a new aspect of BTKi’s that needs to be taken into consideration as we report two cases of life-threatening aplastic anemia upon treatment with the BTKi acalabrutinib for MCL. The two patients were treated with acalabrutinib as first line treatment, patient 1 for a classical MCL with moderate proliferation and patient 2 for an aggressive tumor with blastoid morphology, p53 overexpression and high proliferation rate. Both patients had excellent tumor responses but within a few months they presented with trombocytopenia that quickly led to a fulminant pancytopenia. Acalabrutinib treatment was stopped immediately but the pancytopenia did not resolve. Investigations led to the diagnosis of the autoimmune disease aplastic anemia in both cases. Patient 1 died of neutropenic infection shortly after the diagnosis. Patient 2 was treated successfully with immunosuppression and regained near to normal blood counts, but subsequently developed relapsed MCL. Autoimmune diseases in general are overrepresented in patients with lymphoma, and there are reports of other autoimmune anemias such as autoimmune hemolytic anemia being triggered by lymphoma treatment. Aplastic anemia however, has never previously been reported as a potential side effect of BTKi in MCL. There is a possibility that this condition is underrecognized and mistaken for progression of tumor infiltration in the bone marrow. Aplastic anemia should be taken into consideration when patients present with pancytopenia during treatment with BTKi.