Salvage Treatment with Lenalidomide and Dexamethasone in Patients with Relapsed Refractory Mantle Cell Lymphoma.

Previous reports have highlighted the activity of Lenalidomide (Len) in patients with relapsed or refractory mantle cell lymphoma (MCL), achieving a 53% overall response rate (ORR), which included 20% complete responses (CR) (Haberman et al. Br J Haematol. 2009). In vitro studies on Burkitt's Lymphoma and MCL cell lines showed that combining Dexamethasone (Dex) with Len results in potent and synergistic anti-proliferative effects. To assess whether this effect translates to a clinical setting, and on the basis of data coming from multiple myeloma, we initiated a prospective, multicenter, phase II study, to evaluate safety and efficacy of Len administered in combination with Dex for adult patients with relapsed or refractory MCL.

Patients had to have ≥1 prior treatment regimen, and were either not eligible for, or had relapsed after, more intensive treatments including stem cell transplantation (SCT). During the induction phase (month 1 to 3), patients received Len 25 mg/day on days 1 to 21 and Dex 40 mg/day on days 1, 8, 15, 22 of a 28-day cycle (Len Dex). Enoxiparin 4.000 U/day was administered as anti-thrombotic prophylaxis. Patients who achieved a partial response (PR) or stable disease (SD) at the end of the induction phase continued to the consolidation phase, which consisted of treatment with Len Dex until disease progression, unacceptable toxicity, or a CR, for a maximum of 12 months. Patients with a CR at the end of the induction phase, or those who achieved a CR during consolidation, received an additional 3 courses of Len Dex. The primary objective is to evaluate the ORR and CRR (IWG criteria Cheson et al 2007). Secondary objectives include safety, response duration (RD), overall survival (OS), and to explore changes in tumour biomarkers relative to response to treatment with Len Dex. Severity of adverse events (AE) is graded on a scale of 1 to 5 (NCI CTCAE v.3).

Between July 2008 and July 2009, 33 patients were enrolled on this study, representing the intent to treat population. Patients' median age is 68 years (range 51-80); 30 have the classic histology while 3 patients have the blastoid variant; 9 patients previously received two lines of therapy, 9 patients had three lines and 12 patients had >3 prior lines (median 3; range 1-7). Twelve patients previously underwent an autologous SCT and 7 received prior therapy with Bortezomib. At present, 21 out 33 enrolled patients are evaluable for response to the induction phase of the study: 11 patients responded to Len Dex (52% OR), including 3 CRs (14%); 1 patient (5%) has SD and 9 patients (43%) either had not responded or had progressed while on study. Nine patients discontinued treatment for the following reasons: skin reaction in 1 patient, progression in 7 patients, 1 patient died while on study. So far, 28 patients are valuable for safety during the induction phase. Most common Grade 3-4 adverse events were hematologic and included leucopenia (n=6; 21%), neutropenia (n=10; 36%), thrombocytopenia (n=4; 14%) and anemia (n=1; 3%). Other events included 3 patients (10%) with grade 3-4 neutropenic fever and 2 patients (7%) with grade 3 bacterial pneumonia. Grade 3-4 hypotension and dyspnea developed in 1 patient each, and none of the patients developed thromboembolic or neuropathic complications. Initial results from this study confirm the high therapeutic activity of Len in patients with relapsed and refractory MCL.

Preliminary evaluation of the safety and efficacy of the Len Dex regimen indicates that the combination has a favourable safety profile, but the addition of Dex does not appear to substantially improve the activity of Len in the treatment of patients with relapsed or refractory MCL.

Off Label Use: Lenalidomide is off label for treatment of Non Hodgkin Lymphoma.. Vitolo:Celgene: Lecture fees.