Bortezomib plus rituximab versus rituximab alone in patients with relapsed, rituximab-naive or rituximab-sensitive, follicular lymphoma: A randomised phase 3 trial

The Lancet Oncology, 07/07/2011

Coiffier B et al. – A regimen of bortezomib plus rituximab is feasible. The improvement in progression-free survival provided by this regimen versus rituximab alone was not as great as expected. The regimen might represent a useful addition to the armamentarium, particularly for some subgroups of patients.

Methods

  • Multicentre phase 3 trial, rituximab-naive or rituximab-sensitive patients aged 18 years or older with relapsed grade 1 or 2 follicular lymphoma were randomly assigned (1:1) to receive five 35-day cycles consisting of intravenous infusions of rituximab 375 mg/m2 on days 1, 8, 15, and 22 of cycle 1, and on day 1 of cycles 2—5, either alone or with bortezomib 1·6 mg/m2, administered by intravenous injection on days 1, 8, 15, and 22 of all cycles

Results

  • Between April 10, 2006, and Aug 12, 2008, 676 patients were randomised to receive rituximab (n=340) or bortezomib plus rituximab (n=336)
  • After median follow-up of 33·9 months (IQR 26·4—39·7), median PFS 11·0 months (95% CI 9·1—12·0) in rituximab group and 12·8 months (11·5—15·0) in bortezomib plus rituximab group (HR 0·82, 95% CI 0·68—0·99; p=0·039)
  • Magnitude of clinical benefit not as large as anticipated prespecified improvement of 33% in PFS
  • Patients in both groups received median of 5 treatment cycles (range 1—5); 245 of 339 (72%) and 237 of 334 (71%) patients in rituximab and bortezomib plus rituximab groups completed 5 cycles
  • Of patients who did not complete 5 cycles, most discontinued early because of disease progression (77 [23%] patients in rituximab group, and 56 [17%] patients in bortezomib plus rituximab group)
  • Rates of AE of grade 3 or higher (70 [21%] of 339 rituximab-treated patients vs 152 [46%] of 334 bortezomib plus rituximab treated patients), and serious AE (37 [11%] patients vs 59 [18%] patients) lower in rituximab group than in combination group
  • Most common AE of grade 3 or higher were neutropenia (15 [4%] patients in rituximab group and 37 [11%] patients in bortezomib plus rituximab group), infection (15 [4%] patients and 36 [11%] patients, respectively), diarrhea (no patients and 25 [7%] patients), herpes zoster (one [<1%] patient and 12 [4%] patients), nausea or vomiting (two [<1%] patients and 10 [3%] patients, respectively) and thrombocytopenia (2 [<1%] patients and 10 [3%] patients)
  • No individual serious AE reported by more than 3 patients in rituximab group; in bortezomib plus rituximab group, only pneumonia (7 patients [2%]) and pyrexia (6 patients [2%]) reported in more than 5 patients
  • In bortezomib plus rituximab group 57 (17%) of 334 patients had peripheral neuropathy (including sensory, motor, and sensorimotor neuropathy), including 9 (3%) with grade 3 or higher, compared with three (1%) of 339 patients in rituximab group (no events of grade ?3)
  • No patients in rituximab group but 3 (1%) patients in bortezomib plus rituximab group died of AE considered at least possibly related to treatment

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