A promising new regimen for the treatment of advanced extranodal NK/T cell lymphoma

Extranodal NK/T cell lymphoma (ENKTL) is a distinct entity in the World Health Organization (WHO) classifi cation that is almost always associated with Epstein-Barr virus (EBV) infection and is more common among Asians. Although local radiotherapy is fairly effective in controlling early stage ENKTL, prognosis is dismal for patients with advanced stage ENKTL [1]. Currently, there is no standard fi rst line therapy for the treatment of advanced ENKTL. Anthracyclinebased regimens such as CHOP (cyclophosphamide, doxorubicin, vinciristine and prednisolone) yield dismal response rates ( 15%), partly because the neoplastic NK cells over-express p-glycoprotein, a mediator of the multidrug resistance (MDR) phenotype [2]. Other novel regimens incorporating L-asparaginase have reported better results [3] but await further confi rmation. We present a 30-year-old lady with advanced ENKTL who achieved complete response with a novel treatment regimen after progressing through L-asparaginase based chemotherapy. Our patient presented with a fi ve month history of fever, left eye redness and neck swelling. Computed tomography (CT) revealed generalized lymphadenopathy involving cervical, axillary, paratracheal, para-aortic, iliac and inguinal nodes as well as massive hepatosplenomegaly with splenic infarcts. Magnetic resonance imaging (MRI) brain/orbits showed no intracranial disease. The EBV DNA titre at diagnosis was 11 297 copies/ml. Biopsies taken from the nasopharyngeal soft tissue mass and the left submandibular lymph node revealed a neoplastic lymphoid population that expressed the pan-T cell markers CD2 and CD3, the NK cell marker CD56 and the cytotoxic molecule TIA1, with in situ hybridization for EBV encoded RNA (EBER) strongly positive. Bone marrow trephine biopsy revealed similar histological fi ndings. The patient thus had Stage IV nasal ENKTL, with an international prognostic index (IPI) score of 3 (elevated lactate dehydrogenase, advanced Ann Arbor Stage and multiple extranodal disease sites). She was started on an L-aspariginase based regimen that comprised dexamethasone, methotrexate, ifosfamide, L-asparaginase and etoposide (SMILE), a combination that had previously shown promising results in Phase I studies for patients with advanced or refractory ENKTL [2]. The chemotherapy was given over 14 days with growth factor support, and repeated every 28 days. Disease response was evaluated clinically, radiologically with positron emission tomography (PET)-CT, and with serial EBV DNA titres. Despite initial response, there was disease progression following cycle 3 of SMILE, with rising EBV DNA titres. Her treatment was also complicated by methotrexate retention and prolonged neutropenia. Treatment was then switched to a novel regimen comprising bortezomib, gemcitabine, ifosfamide and oxalipaltin (B-GIFOX) given over four days with growth factor support, repeated every two weeks. PET CT after two cycles revealed near complete response, with EBV titres rendered undetectable for two consecutive readings (see Figure 1). The chemotherapy was well tolerated with no signifi cant hematologic or extra-hematologic toxicities. The patient received a total of four cycles of chemotherapy with a progression free survival of two months.