Sixteen studies were included in the review; six prospective studies (n=138 patients), nine retrospective studies (n=388 patients) and one pilot study (n=9 patients). Sample sizes ranged from 9 to 193 patients, with most studies having less than 35 participants.
Rituximab as second-line therapy (n=114 patients, five studies): Two retrospective studies and three prospective studies assessed rituximab monotherapy for second-line treatment, with response rates ranging from 44 to 64%. The largest prospective study reported a median survival of 15 months and an overall response rate of 68% at one year after treatment.
Chemotherapy as second-line therapy (n=307 patients, six studies): One prospective study, four retrospective studies and one pilot study assessed chemotherapy alone for second-line treatment, with response rates ranging from 25% to 83%. The prospective study was small and reported the largest overall response rate (83%).
Rituximab plus chemotherapy as second-line therapy (n=66 patients, three studies): Two prospective and one retrospective study assessed chemotherapy combined with rituximab for second-line therapy. Both prospective studies reported high overall response rates of 83% and 100%, whilst the retrospective trial reported a response rate of 68%, increasing to 74% 27 months after treatment.
First-line therapy comparisons (n=65): Three studies, all small retrospective studies, assessed chemotherapy alone, rituximab alone or a combination of therapies for first-line therapy. Overall response rates were similar to those reported previously.
Adverse events: Serious adverse events were more frequently reported for chemotherapy as compared to rituximab and ranged from grade 3 neutropenia to infection resulting in death.
Where available data relating to complete response rates and survival were also reported in the review.