A combination of Rituxan (rituximab), Revlimid (lenalidomide), and Bendeka (bendamustine) (R2B) may be a viable option for treating relapsed or treatment-resistant mantle cell lymphoma, a study suggested.
A Phase 2 clinical trial (NCT01737177) demonstrated that, after two years, about half of patients had not relapsed further.
While the study presented impressive results, the researchers argued that it is difficult to compare them with results of earlier trials. More research is needed to decide whether a combination- treatment approach is effective, they said.
The study, “Second-Line Rituximab, Lenalidomide, And Bendamustine (R2B) In Mantle Cell Lymphoma: A Phase 2 Clinical Trial Of The Fondazione Italiana Linfomi,” was published in the journal Haematologica.
Researchers at Azienda Sanitaria-Universitaria Integrata in Italy recruited 42 mantle cell lymphoma patients from cancer clinics in the country. The study was divided into induction, consolidation, maintenance, and follow-up phases.
During the induction or start-up phase, patients received two cycles of R2B for 28 days each. The therapies were administered in a predefined schedule. Patients who failed to progress received two additional rounds of treatment.
Those with a complete or partial response during the induction phase entered the consolidation phase, in which they received two treatment rounds with Rituxan and Revlimid. Those who responded moved on to the maintenance phase.
It consisted of Revlimid only, according to a fixed schedule. The treatment was again given in cycles of 28 days, and continued until a patient progressed or had unacceptable side effects. Patients in this phase received a maximum of 18 rounds of Revlimid.
Patients were then followed for a median of 29 months.
The key measure of the trial’s success was the number of patients with a complete response after consolidation treatment. By then, patients had been treated for about six months. The study showed that 58 percent had a complete response by then. After 24 months, the number was 55 percent.
The median progression-free survival time was 20 months. At 12 months, 64% had survived with signs of progression; at 18 months, 59%, and at 24 months, 43%. The overall survival rates at these time points were 83%, 71%, and 67%.
At the end of the consolidation phase, 71% showed no signs of minimal residual disease in the blood, and 36% showed no minimal residual disease in bone marrow samples.
Measurements of minimal residual disease in peripheral blood at the end of the induction phase could not predict how well a patient would fare in the long run, but being free of minimal residual disease in bone marrow was a predictor of longer progression-free survival.
The safety of the combination treatment was also assessed. The most common grade 3 or 4 adverse events during the first two phases were low numbers of neutrophils — a type of white blood cell — or loss of neutrophils accompanied by fever, and lower numbers of platelets, or clotting cells. Lung and kidney toxicity, as well as anemia, was seen in a smaller number of participants.
Fifteen patients died during the follow-up period. None of the deaths was related to the treatment.
Despite assessing several factors for their potential as markers of treatment response, researchers could not identify any predictors.