Maintenance Therapy with Rituximab Prolongs the Progression-Free Survival in Follicular Lymphoma. Results from the PRIMA trial

Sari Riihijarvi

Follicular lymphoma (FL) is the most common indolent lymphoma in the Western countries. It is considered rarely curable with conventional chemotherapy due to its tendency to relapse. FL maintains sensitivity to different chemotherapeutic agents for several years but ultimately becomes resistant or transforms into a high-grade lymphoma. The median survival has been in the range of 8 to 10 years.

In the past ten years rituximab, a monoclonal anti-CD20 antibody, has revolutionised the management of B-cell lymphomas. A significant improvement in the outcome of FL patients has been obtained by combining rituximab with induction chemotherapy, or by prolonging the remission with rituximab maintenance therapy.

Despite the recent advances, the optimal dosing and the treatment schedule of rituximab remains unknown.

In the Lancet, Gilles Salles et al. report the initial outcome of the PRIMA trial, the largest randomised study ever in follicular lymphoma. PRIMA trial was phase III randomised open-label multicentre study covering over 200 centres in 25 countries.

The trial enrolled 1217 patients. All the patients were diagnosed with previously untreated follicular lymphoma and had indications for therapy (bulky disease, symptoms, laboratory abnormalities). 80% had intermediate-risk or high-risk scores on follicular lymphoma international prognostic index (FLIPI).
The patients received induction therapy with rituximab plus chemotherapy. Most patients (75%) were treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) which is considered nowadays the standard of care. Two other chemotherapy regimens were also used.
16% of the patients who received the induction therapy did not proceed to randomisation, largely due to treatment toxicity. Ultimately, 1019 patients were randomised  to 2 years of rituximab maintenance therapy versus observation. Maintenance rituximab was given as a single dose every 8 weeks.

Patients receiving rituximab maintenance therapy had significantly better rates of 3-year progression-free survival when compared to the observation arm (75% versus 58%). All FLIPI groups benefited from the maintenance therapy. Time to next lymphoma treatment was also longer in the maintenance group than in the observation group, although single-agent rituximab was an treatment option in the observation group. Not surprisingly, there was more toxicity in the maintenance group, with most increased effects being infections. The toxicity was mostly slight and self-limiting.

The results are convincing, although a longer follow-up is needed to asses the impact of maintenance therapy to overall survival. In an indolent disease with multiple relapses and treatments, only longer overall survival will ultimately confirm whether all patients benefit from maintenance therapy.

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