LONDON – Rituximab more than doubled the duration of remission in elderly patients with mantle cell lymphoma when used as maintenance therapy in those who had already responded to induction therapy in a large, randomized controlled trial.
First results from the European Mantle Cell Lymphoma (MCL) Network study show that rituximab maintenance is associated with a median remission of 77 months. In comparison, when interferon (IFN) was used as maintenance, the median was 24 months (hazard ratio, 0.54; P = .0109).
Overall survival data are not yet fully mature but suggest that rituximab (Rituxan in the United States, Mabthera in Europe) improves upon the rates achievable. At 4 years’ follow-up, 62% of patients treated with IFN and 77% of those maintained on rituximab were still alive. This difference was not statistically significant, however.
Rituximab is not licensed for the treatment of MCL in Europe or the United States.
"Rituximab after R-CHOP [rituximab, cyclophosphamide (Cytoxan), hydroxydaunorubicin (doxorubicin, Adriamycin), Oncovin (vincristine), and prednisolone] should become the new standard for elderly MCL patients to which new regimens should be compared," said study investigator Dr. Hanneke C. Kluin-Nelemans of the University Medical Center of Groningen, the Netherlands, while reporting the findings at the annual congress of the European Hematology Association.
"MCL is a disease of the elderly," Dr. Kluin-Nelemans observed. More than 60% of patients with MCL are aged 60 years or older, and treatment options can be limited. High-dose chemotherapy and autologous stem cell transplantation are not always possible, and "almost all patients relapse" after initial immunochemotherapy. Furthermore, overall survival is about 3-5 years in those who are aged 60 years and up, Dr. Kluin-Nelemans said.
Patients in the trial had previously received induction therapy with R-CHOP or R-FC (rituximab plus fludarabine with cyclophosphamide).
The study consisted of two randomization phases, the first of which saw 560 newly diagnosed, fit (performance status 0-2), elderly patients with MCL treated with either eight cycles of R-CHOP or six cycles of R-FC. The 310 patients who responded to either regimen entered the second randomization phase – this time to treatment with single-agent IFN or rituximab alone as maintenance therapy. IFN was given as 1-3 doses/week depending on the formulation used (IFN-alpha or peg-IFN), and rituximab (375 mg/m2) was given as a single dose every 2 months until disease progression.
The study was closed early in October 2010 under the advisement of the trial’s Data Safety Monitoring Board, as the data favored rituximab over IFN as maintenance therapy, and the R-CHOP regimen was clearly better than R-FC regimen.
Per-protocol results showed a significant improvement in remission during maintenance treatment with rituximab vs. IFN. These data remained significant in an intent-to-treat analysis.
The investigators also looked to see what effects the induction regimens could have on the maintenance phase results, and found that the duration of remission was significantly better in patients who received R-CHOP than in those given R-FC.
Dr. Kluin-Nelemans was questioned after her presentation as to that lack of a placebo-controlled arm. In response, she said that an analysis had looked at 87 of 250 patients who were not randomized to maintenance treatment. All had stopped rituximab treatment before they could be randomized, and were thus a population of patients that could potentially benefit.
Rituximab was associated with significantly less fatigue (P less than .001) and fewer infections (P less than .022), and was less likely to decrease white blood cell and platelet counts (P less than .001) than IFN. The rate of more serious infections was also lower than with IFN (P less than .022)
Considering the efficacy findings and the fact that there was also low toxicity associated with rituximab compared with IFN, these data suggest that the CD-20-targeting agent could be a better option for maintenance therapy than other biologic or immunomodulatory agents.
"We have shown it’s possible to do a large [randomized controlled trial] with two randomization steps in fit, elderly patients with MCL," Dr. Kluin-Nelemans said. "Rituximab more than doubles the remission duration in patients depending upon initial therapy."
Dr. Kluin-Nelemans stated that she had no conflicts of interest related to her presentation.