The efficacy and toxicity of readministration
of rituximab (Rituxan) in patients with indolent B-cell
non-Hodgkins lymphoma (NHL) that recurs after an initial
response to rituximab are unknown. We conducted a multicenter, phase
II study of rituximab in indolent CD20-positive B-cell NHL. The
present study attempts to investigate the safety and efficacy of
readministration of rituximab.
From July 1997 to November 1998, patients with relapsed, indolent,
CD20-positive B-cell NHL, revised European-American Lymphoma (REAL)
type II-1, 2, 3, 4, 5, and 6 histology, all of whose pathology was
confirmed by central review, were treated with rituximab at 375
mg/m² × 4 weekly infusions as a phase II study in Japan.
Rituximab produced a 59% response rate (95% confidence interval [CI],
41% to 71%) Retreatment was planned for responsive patients who
showed stable disease (SD), partial response (PR), or complete
response (CR) after the initial treatment. To be eligible for
retreatment, patients were required to meet the same criteria as for
a phase II study.
Nine patients were retreated with identical courses of rituximab.
Five patients who received rituximab (250 or 375 mg/m² × 4
weekly infusions) in the preceding phase I study were also entered
into this study. All 14 patients eligible for retreatment had stage
IIIA or IVA disease and had an International Prognostic Index (IPI),
placing them in a low- or low-intermediate risk group. The median
follow-up time was 19 months (range, 15 to 33 months). Of the 14
patients, 11 had follicular lymphoma; 1, mantle cell lymphoma; and 2,
diffuse large B-cell lymphoma.
Rituximab retreatment was well tolerated, with no grade 3-4
nonhematologic toxicity, similar to initial therapy. One patient
developed grade 3 neutropenia. One patient died of disease
progression. All patients experienced rapid B-cell decrease, which
lasted for more than 4 months. No patient developed human antimouse
antibody (HAMA) and human antichimeric antibody (HACA) reactions
after retreatment. T-cell counts and serum immunoglobulin levels did
not decrease during the follow-up period.
Responses to retreatment were seen in 5 of 14 patients (36%; 95%
CI,12% to 64%); 7patients had SD; and 2 experienced progressive
disease (PD). Overall survival rate was 93% at 19 months. Median time
to progression (TTP) after retreatment was 5 months, while median TTP
after initial treatment was 8 months.
There was no significant correlation between TTP after initial
treatment and that after the second treatment. Three patients who
received more than three courses of retreatment continue to show response.
CONCLUSION: Rituximab is effective for relapsed, indolent,
CD20-positive B-cell NHL after initial rituximab treatment and can
produce prolonged failure-free survival without major toxicities.