Treatment of Indolent, Recurrent B-Cell Non-Hodgkin Lymphoma

In general, treatment with standard agents rarely produces a cure in patients with relapsed B-cell non-Hodgkin Lymphoma (NHL). Sustained remissions after relapse can often be obtained in patients with indolent lymphomas, but relapse will usually ensue. Favorable survival after relapse has been associated with an age younger than 60 years, complete remission rather than partial remission, and duration of response longer than 2 years.[1] Even patients in the most favorable subset, however, have a tenfold greater mortality compared with age-adjusted U.S. population rates.[2]

Patients who experience a relapse of indolent lymphoma can often achieve disease control with single-agent or combination chemotherapy, rituximab (an anti–CD20 monoclonal antibody), lenalidomide, radiolabeled anti–CD20 monoclonal antibodies, or palliative radiation therapy.[3,4] However, long-term freedom from second relapse is uncommon and multiple relapses usually occur. Patients with indolent lymphoma may experience a relapse with a more aggressive histology. If the clinical pattern of relapse suggests that the disease is behaving in a more aggressive manner, a biopsy can be performed. If a more aggressive histology is confirmed, therapy must change to a regimen applicable to that histological type.[5] Rapid growth or discordant growth between various disease sites may indicate a histological conversion.

In a retrospective review of 325 patients diagnosed between 1972 and 1999, the 10-year risk of histological transformation was 30%.[6] In this series, high-risk factors for subsequent histological transformation were advanced stage, high-risk Follicular Lymphoma International Prognostic Index, and watchful waiting (as opposed to treatment being initiated at diagnosis). The median survival after transformation was 1 to 2 years, with 25% of patients alive at 5 years and with approximately 10% to 20% of patients alive 10 years after re-treatment.[7]

A prospective trial of 631 patients with follicular lymphoma and with a median follow-up of 60 months in the rituximab era (2002–2009) found a 5-year transformation rate to a higher-grade histology of 11%.[8] The median overall survival (OS) after transformation was 50 months, and the 5-year OS rate was 66%, if the transformation occurred more than 18 months after a diagnosis of follicular lymphoma. This series described a better prognosis for patients with transformation than in the era before rituximab.

For descriptions of the regimens used to treat histological conversions, see the Treatment of Aggressive, Recurrent B-Cell Non-Hodgkin Lymphoma section in Aggressive B-Cell Non-Hodgkin Lymphoma Treatment. The durability of the second remission may be short, and clinical trials can be considered.