Alectinib Monotherapy in Isolated Central Nervous System Relapse of ALK-Positive Anaplastic Large Cell Lymphoma

Abstract

Anaplastic lymphoma kinase-positive anaplastic large cell lymphoma (ALK-positive ALCL) is an aggressive form of peripheral T cell lymphoma (PTCL), harbouring an underlying pathogenic ALK fusion gene that produces a constitutively activated tyrosine kinase. The ALK tyrosine kinase provides a targeted treatment option in the form of ALK inhibitors. ALK-positive ALCL may rarely involve the central nervous system (CNS), either at presentation or on relapse of disease. The outcomes of CNS relapse in PTCL are historically extremely poor. We present a case of a 20-year-old man diagnosed with stage IVB ALK-positive ALCL. He responded favourably to six cycles of cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone (CHOEP). He unfortunately relapsed with isolated CNS involvement only 3 weeks after completing his sixth cycle of CHOEP chemotherapy. The CNS-penetrating ALK inhibitor alectinib was identified as a targeted treatment option, as he was not a candidate for CNS-penetrating chemotherapy due to significant iatrogenic renal impairment. After commencing alectinib monotherapy, he rapidly achieved a clinical and radiological response. He has now remained in a durable remission for more than two years on alectinib monotherapy.

Figure 1

MRI brain at time of relapse (August 2019), on the left, demonstrating a 3.4 cm enhancing lesion within the parietal region with associated leptomeningeal enhancement. On the right, a repeat MRI brain (January 2020) after 3 months on alectinib monotherapy showing resolution of lesion and leptomeningeal enhancement.

Figure 2

Cerebrospinal fluid analysis at time of isolated CNS relapse in August 2019 showing diffuse involvement by lymphoma cells.