Crizotinib in ALK-Positive Diffuse Large B-Cell Lymphoma: A Case Report

Anaplastic lymphoma kinase (ALK)-positive diffuse large B-cell lymphoma (DLBCL) displays a rare and distinct variant of DLBCL characterized by very aggressive clinical course with an estimated median survival of only 11.0 months. Crizotinib, an ALK inhibitor, has demonstrated impressive clinical efficacy in patients with alk-rearranged tumors such as NSCLC. The potential role of Crizotinib in ALK-positive DLBCL has not been established yet.

A 27-year-old female patient with initial advanced-stage IV ALK-positive DLBCL was primary refractory to 6 cycles of standard chemotherapy with CHOP. She was subsequently treated with different salvage combination chemotherapy regimens including high-dose chemotherapy with autologous stem-cell transplantation. However, disease followed a very aggressive course and relapse occurred fast after each regimen. 6 weeks after transplantation patient presented with right cervical lymphadenopathy and multiple cutaneous lesions. CT scan revealed additional bilateral cervical, axillary, mediastinal and abdominal lymphadenopathy and involvement of lung and liver. LDH levels were exorbitant elevated (233 mmol/l). On an individual base, our patient received the ALK inhibitor Crizotinib 250 mg per os twice daily. No glucocorticoids or other drugs with antineoplastic activity were co-administered. Within 72 hours LDH levels were halved (89 mmol/l). On day 8 cervical palpable lymphadenopathy disappeared. Initial erythematous papular cutaneous lesion decreased from 4.0 × 2.5 cm to a residual hyperpigmented macule of 1.5 × 2.5 cm. On day 16 LDH levels were almost within normal limits (6 mmol/l). However, remission was not sustained and patient developed resistance to Crizotinib. By day 21 after beginning the treatment with Crizotinib LDH levels increased again and patient presented with a swollen left arm due to lymphatic obstruction, detected by CT scan, which showed a general progressive disease, causing death one month later.

To our knowledge, this is the first case which reports sensitivity in ALK-positive DLBCL to ALK inhibition with Crizotinib. Despite remission duration was short our results indicate a potential role of ALK in the pathogenesis of ALK-positive DLBCL and suggest ALK inhibition as a potentially promising treatment modality in the therapy of this rare and fatal disease.

Off Label Use: Crizotinib is an ALK inhibitor, indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that is anaplastic lymphoma kinase (ALK)-positive. Recently impressive clinical efficacy of Crizotinib has been reported in two patients with ALK-positive anaplastic large cell lymphoma. Based on these data we initiated the treatment with Crizotinib in our patient, who showed very aggressive clinical behavior and fulminant early recurrence of a ALK-positive diffuse large B-cell lymphoma after salvage chemotherapy regimens on an individual base.