Rituximab–lenalidomide–dexamethasone induces complete and durable remission in relapsed refractory diffuse large B-cell non-Hodgkin lymphoma

Since the first and subsequent reports of its efficacy in myelodysplastic syndrome and multiple myeloma, there has been growing interest in lenalidomide as an anti-lymphoma therapy. Data emerging from initial clinical trials has demonstrated that lenalidomide has significant activity against different subtypes of aggressive B-cell lymphoma [1,2]. Two phase 2 studies of lenalidomide monotherapy in patients with relapsed or refractory aggressive non-Hodgkin lymphoma (NHL; diffuse large B-cell [DLBCL], grade 3 follicular lymphoma, mantle-cell [MCL], and transformed NHL) were conducted in the USA (NHL-002) [3] and internationally (CC-5013-NHL003) [4]. The first study (49 patients) demonstrated a 35% overall response rate (ORR), which included 12% of patients with complete response, and a median duration of response (DR) of 10.4 months. The larger (217 patients) CC-5013-NHL-003 study confirmed these results in a similar patient population. Clinical responses were histologic subtypedependent and most prominent in MCL: ORR was 53%, with 20% CR and 33% PR. Median duration of response was 13.7 months and median progressionfree survival (PFS) was 5.6 months [5]. The results in patients with DLBCL (n1⁄4 108) were less encouraging, with ORR of 28%, short median PFS of 2.3 months, and median DR of 4.5 months. However, given the dismal prognosis of patients with relapsed DLBCL, this activity prompted us to utilize a lenalidomide-based combination in a single patient. Herein we report the case of a patient with DLBCL who was refractory to four previous lines of conventional immuno-chemotherapy, but achieved a remarkable sustained complete remission to treatment using the combination of lenalidomide with rituximab and dexamethasone. A 65-year-old male presented with 2 months’ history of abdominal pain and diarrhea. Colonoscopy revealed a left colon tumor, and biopsy showed histopathological features of DLBCL: proliferation of large immunoblastic and centroblastic cells expressing CD20 but also BCL2 and MUM1 without expression of CD10 and BCL6. The disease was classified by immunochemistry as ‘non-germinal center B-cell’ (non-GCB) according to the Hans decision tree [6]. The patient was staged as Ann Arbor IV, and received eight cycles of standard RCHOP-21 chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, 21day cycle). Complete response was confirmed by fluorodeoxyglucose positron emission tomographycomputed tomography (FDG PET-CT) and biopsy at the end of chemotherapy. The first relapse of DLBCL occurred 7 months later, and was confirmed by a new colon biopsy. The patient received two cycles of R-DHAC-21 (rituximab, carboplatin, cytarabine, and dexamethasone) as second-line treatment. After two cycles, the colonoscopy remained