Patients with follicular lymphoma and marginal zone lymphoma who failed at least one prior therapy live significantly longer — more than two years — without their disease worsening when treated with a combination of Revlimid (lenalidomide) and Rituxan (rituximab), compared to Rituxan alone, a Phase 3 trial shows.
The combination was also superior in many other measures, including the number of patients responding to treatment, proportion of complete responses, duration of response, and time to next lymphoma treatment. While not powered to detect differences in overall survival, the trial also suggests that the combination reduces the risk of death by 39%.
The study, “AUGMENT: A Phase III Study of Lenalidomide Plus Rituximab Versus Placebo Plus Rituximab in Relapsed or Refractory Indolent Lymphoma,” was published in the Journal of Clinical Oncology.
Rituxan, alone or in combination with chemotherapy, is the standard therapy for non-Hodgkin’s lymphoma patients who have failed prior treatments. Rituxan, by Genentech and Biogen, is an antibody that targets the CD20 molecule, widely produced by lymphoma cells.
Response rates to Rituxan alone are 40–60%, but rise as high as 90% when it is used along with chemotherapy. However, chemotherapy is known to cause toxicity and to compromise the immune system, increasing patients’ risk of infection.
Celgene’s Revlimid (lenalidomide) has appeared as promising for non-Hodgkin’s lymphoma patients, showing response rates of 65–77% when used in combination with Rituxan.
Thus, researchers at Celgene designed a Phase 3 trial, called AUGMENT (NCT01938001), to determine whether adding Revlimid to Rituxan would delay disease progression or death among follicular and marginal zone lymphoma patients who had failed at least one prior treatment with chemotherapy or immunotherapy.
AUGMENT included 358 patients — 295 with follicular lymphoma and 63 with marginal zone lymphoma, median age 63 years — who randomly received either the combination or Rituxan plus a placebo.
In addition to the time patients lived without their disease worsening — the trial’s main goal — researchers also examined response rates, overall survival, adverse events, and time to next anti-lymphoma therapy as secondary measures.
Results showed that patients given the combination lived significantly longer without their disease worsening (median 39.4 months) compared to Rituxan (14.1 months). This 25-month extension represented a 54% reduction in the risk of disease progression or death.
Investigators also found that more patients responded to the combination than to Rituxan only (78% vs. 53%) and more patients achieved a complete response (34% vs. 18%).
Additional secondary endpoints were all superior in the combo therapy, including duration of response (36.6 months vs 21.7 months) and event-free survival (27.6 months vs. 13.9 months). After a median follow-up of 28.3 months, the risk of needing a subsequent lymphoma therapy or a chemotherapy, and the risk of disease progression or death on that therapy, was cut by half with the combination.
The trial was not powered to assess overall survival, but the estimated 2-year survival was 91% for those on the Revlimid group versus 87% for Rituxan only.
Adverse events more common in the combination group included infections (63% vs. 49%), low level of neutrophils (58% vs. 23%), and skin reactions (32% vs. 12%). Four patients died because of adverse reactions, two in each group.
Overall, these results confirm early findings and suggest that “lenalidomide plus rituximab should replace rituximab monotherapy as a standard of care for patients with relapsed or refractory indolent NHL,” the study concluded.
