title: Bendamustine produces durable responses with an acceptable safety profile in patients with rituximab-refractory indolent non-Hodgkin lymphoma.
abstract: BACKGROUND
  Although initially responsive to therapy, indolent non-Hodgkin lymphomas (NHLs) are generally incurable. Therefore, active and tolerable treatments for patients with relapsed or refractory disease are needed. Bendamustine, a mechlorethamine alkylator with novel mechanisms of action, is approved in the United States for rituximab-refractory indolent B-cell NHL.
  
  
  METHODS
  Data from 2 North American multicenter studies with similar design, enrollment, and response criteria were pooled to evaluate safety and durability of response. Bendamustine was administered at 120 mg/m2 days 1 and 2 every 21 days for 6-8 cycles. Endpoints included overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and safety.
  
  
  RESULTS
  The studies enrolled 161 patients with a median of 2 previous chemotherapy regimens. Histologies included follicular (68%), small lymphocytic (20%), marginal zone (11%), and lymphoplasmacytic (1%) lymphoma. Sixty patients (34.1%) were refractory to their last chemotherapy, 53 (30.1%) were alkylating agent refractory. Overall response rate was 76% with 23% complete remissions (CRs) and unconfirmed CR (CRu). The median follow-up was 25.3 months (range, 24-27.8 months) and DOR was 10 months (range, 8.3-14 months). At 1 and 2 years, 45% and 23% of responders continued to respond. Among 127 patients previously treated with alkylators, ORR was 88% (28% CR/CRu) in responsive and 59% (12% CR/CRu) in refractory patients. Fifty opportunistic infections were reported in 48 patients. Second malignancies occurred in 9 patients (5.6%; 5 myelodysplastic syndromes, 2 acute myelogenous leukemia, 1 chronic myelomonocytic leukemia, and 1 squamous cell carcinoma).
  
  
  CONCLUSIONS
  Bendamustine induces durable responses with acceptable long-term safety in rituximab-refractory indolent NHL.
authors.affiliation: Georgetown University Hospital, Lombardi Comprehensive Cancer Center, 3800 Reservoir Road N.W., Washington, DC, USA. bdc4@georgetown.edu
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Cheson
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Friedberg
authors.forename: Brad S
authors.initials: BS
authors.lastname: Kahl
authors.forename: Richard H
authors.initials: RH
authors.lastname: Van der Jagt
authors.forename: Lothar
authors.initials: L
authors.lastname: Tremmel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000139:chemically induced; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000627:therapeutic use; D000069461:Bendamustine Hydrochloride; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D016393:Lymphoma, B-Cell / Q000188:drug therapy*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic / Q000706:statistics & numerical data; D009325:Nausea / Q000139:chemically induced; D009588:Nitrogen Mustard Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D000069283:Rituximab; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D009588:Nitrogen Mustard Compounds; D000069283:Rituximab; D000069461:Bendamustine Hydrochloride