A Multicenter Study Evaluating the Efficacy and Safety of Bendamustine in the Treatment of Mantle Cell Lymphoma

Bendamustine has evolved as an increasingly used chemotherapeutic agent for diverse lymphomas in the United States (US) and Europe. It is an alkylating agent that was approved in the US for use as a first line therapy for chronic lymphocytic leukemia and relapsed indolent B-cell non-Hodgkin's Lymphoma (NHL) in 2008. However, the two pivotal studies that established bendamustine for this indication included only few patients with mantle cell lymphoma (MCL). The goal of this retrospective study was to evaluate efficacy of bendamustine in MCL.

We retrospectively reviewed the records of all MCL patients who were treated with bendamustine at Jackson Memorial Hospital and the Sylvester Comprehensive Cancer Center (both in Miami, FL) and the Stanford Cancer Center (in Stanford, CA). The primary endpoint was overall response rate (ORR) and secondary endpoints were overall survival (OS), time to treatment failure (TTF), and safety.

Thirty MCL patients received bendamustine, 28 in combination with rituximab and 2 as monotherapy. Nineteen of these patients were treated at the University of Miami and 11 at Stanford. The median age at diagnosis was 58 years and 77% of the patients were male. The most common extranodal site of involvement at diagnosis was the bone marrow (57%), followed by the GI tract (33%). Most patients presented with advanced disease, with 69% and 28% of the patients having stage IV and III disease at diagnosis, respectively. Seven patients (23%) were diagnosed with the blastic variant of MCL. Five patients received bendamustine as initial therapy and 25 for relapsed disease. Five of these patients had relapsed MCL after an autologous HSCT The most common schedule was bendamustine 100mg/m² on days one and two and rituximab 375mg/m² on day one of a 28 day cycle, for a median of six cycles. Of the 30 patients, there were fifteen complete responses (CR) and ten partial responses (PR), for an ORR of 83% (95% confidence interval [CI] 70–97%). With a median follow-up of 8 months (range 0.3–29.5 months), the median overall survival (OS) was not reached; the one-year OS rate was 73%; the two year OS rate was 67%. When OS and time to treatment failure (TTF) were stratified by response (using a 2-month landmark as the starting point for analysis), patients achieving a CR had a significantly longer OS and TTF compared to patients who did not achieve a CR (log rank p < 0.001). The TTF and OS were significantly worse for patients with the blastic variant versus the diffuse variant. In 5 patients with relapse post autologous HSCT, bendamustine induced a CR in three and a PR in one other patient. The majority of serious adverse events associated with bendamustine were hematological. Grade 3 or 4 neutropenia, anemia, and thrombocytopenia occurred in 23%, 3%, and 20%, respectively. Common non-hematologic grade 1 or 2 toxicities were fatigue (27%), edema (20%), erythematous rash (20%), and nausea (13%). Two patients developed neurological sequelae during or after treatment with bendamustine. The first patient developed left sided weakness and dysmetria ten months after completing therapy. A brain biopsy revealed progressive multifocal leukoencephalopathy. A second patient developed ataxia and incontinence while on rituximab plus bendamustine therapy and expired before a definitive diagnosis could be established.

Bendamustine appears to have a favorable profile as a second-line agent for patients with relapsed MCL. The response rate is at least comparable to other therapies, especially when examined in light of the toxicity profile seen with other regimens. This study supports the need for continued investigation of bendamustine as a therapy for MCL patients both in the frontline and relapsed settings in prospective clinical trials, some of which are presently ongoing.

No relevant conflicts of interest to declare.