Efficacy and Safety of Bendamustine and Rituximab as First Salvage Treatment in CLL: Results of the GIMEMA-ERIC LLC1315 Study

Conference Correspondent - ASH 2017 - Chronic Lymphocytic Leukemia

In chronic lymphocytic leukemia (CLL), chemoimmunotherapy (CIT) produces high overall response rates (ORRs), and prolonged progression-free survival (PFS) and overall survival (OS).1 In the absence of a TP53 disruption, recent guidelines recommend a CIT regimen in first- and second-line therapy in patients who have attained prolonged PFS with a previous regimen. However, there is uncertainty in the recommendations for first salvage treatment. Because the combination of bendamustine and rituximab (BR) is one of most widely adopted second-line regimens, at ASH 2017, the authors reported on a retrospective study within the GIMEMA-ERIC network on the efficacy and safety of the BR regimen as second-line therapy in a real-world setting.2

A total of 237 CLL patients at 35 GIMEMA-ERIC centers were enrolled. Enrolled patients had relapsed CLL with 1 previous treatment with alkylating agents and/or purine analogs with or without monoclonal antibodies, and progression requiring second-line treatment according to National Cancer Institute criteria, and at least 1 day of second-line treatment with BR (bendamustine 70 mg/m2 days 1-2 and rituximab 375 mg/m2 for the first course and 500 mg/m2 subsequently). The primary end point was PFS at 12 months. The secondary end points were ORR, time to next antileukemic treatment (TTNT), and OS. Of these patients, 21% had advanced-stage disease (ie, Rai III-IV or Binet C), 73% had unmutated IGHV, and 33% had del(11q) and/or del(17p). First-line treatment was CIT in 59% of the cases; the remaining patients received chemotherapy alone. A total of 95 (40%) patients received 6 cycles without dose reduction.

At 12, 30, and 60 months, PFS rates were 79%, 31%, and 16%, respectively. Shorter PFS was observed in patients with del(17p) (P = .0004), unmutated IGHV (P = .0299), and advanced-stage disease (P = .0192). ORR was 82%, but the probability of attaining a response was significantly lower in patients with del(17p) (P = .04). The TTNT at 12 months was 18%, but a shorter TTNT was observed in patients with del(17p) (P = .0215) and in those who received CIT (P = .004) as the first-line regimen. OS at 12 months was 93%. PFS and OS at 12 months for patients without del(17p) were 81% and 92%, respectively.

At least 1 grade 3/4 adverse event was reported in 33% of the patients; neutropenia (including febrile neutropenia) occurred in 21% of cases, thrombocytopenia in 6 patients (2.5%), and anemia in 3 patients (1.2%). Grade 3 to grade 5 infections were recorded in 16 patients, 8 of whom had a lung infection.

The authors concluded that BR is an effective first salvage regimen in CLL except in those patients with unfavorable genetic features, especially del(17p) and/or unmutated IGHV and advanced-stage disease. These data may assist in the selection of the most appropriate first salvage treatment in relapsed CLL.


  1. Fischer K, et al. Blood. 2016;127:208-215.
  2. Cuneo A, et al. ASH 2017. Abstract 4330.
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