Outcomes Research in Review

AUGMENT: Lenalidomide/Rituximab vs Placebo/Rituximab in Relapsed or Refractory Indolent Lymphoma


 

References

Conclusion. The R2 regimen was superior to rituximab and placebo in relapsed or recurrent follicular lymphomas. The regimen’s safety profile was acceptable, with higher events of usual and expected but manageable toxicities in the R2 regimen compared to rituximab/placebo.

Commentary

Nearly half of non-Hodgkins lymphomas (NHLs) diagnosed in the United States are classified as indolent B-cell lymphomas.1 Follicular lymphomas constitute about 50% of all indolent NHLs, while MZLs comprise less than 15%.1 These slowly progressive B-cell lymphomas are currently considered treatable but have very low cure rates. Cure is primarily limited to early stage I/II disease and may be possible in less than half of patients by applying involved-field radiation therapy with curative intent.

More than two thirds of indolent lymphomas present in advanced stages (III-IV). Despite an advanced stage at presentation, initial chemoimmunotherapy can induce complete remission in nearly 60% of patients. Unfortunately, nearly all patients relapse over the next 10 years.2 The wait-and-watch approach is a common strategy, and most patients are administered initial therapy or subsequent lines of therapy if they are symptomatic.2 As such, for the majority of these patients, the goal of therapy is to minimize toxicities, preserve quality of life, treat symptoms, and achieve a long PFS without an attempt to cure. Following each line of therapy, patients often revert to watchful surveillance, sometimes for more than a decade. With additional subsequent lines of therapy, lymphoma tends to get more refractory to treatment.

A median survival of nearly 2 decades has been achieved in advanced follicular lymphomas2,3 and MZL.4 However, wide variation in overall response, duration of response, and survival is reported based on the individual risk profile.

The drug of interest in the present study by Leonard and colleagues, lenalidomide, has immunomodulatory properties and antiproliferative effects, possibly related to its binding of the E3 ligase protein cereblon and subsequent ubiquitination of the transcription factors Aiolos and Ikaros.5 The benefits of combination lenalidomide/rituximab against follicular lymphoma in preclinical settings have been attributed to mechanisms mediated by tumor-infiltrating lymphocytes, natural killer cells, monocytes, and antibody-dependent cell-mediated toxicity.5 The combination has now been studied in first-line and subsequent lines of therapy for follicular lymphoma and MZL.6

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