2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

TREATMENT OPTIONS IN INDOLENT LYMPHOMA
Table 3. Studies Investigating an Anti-CD20 Antibody Consolidation or Maintenance Therapy after Chemotherapy with Rituximab
Reference Induction txa n per arm Median
PFS
Intervention (control/intervention) follow-up HR (95% CI) Control Intervention
Hagenbeek et al (37) Chemotherapyb 90Yibritumomab tiutexan 202/207 66 mo 0.51 (0.4–0,66) 15 mo (median) 49 mo (median)
Salles et al (29) R-CVP rituximab maintenance
113/109 48 mo 0.71 (0.48–1.04) 47% (4-y) 60% (4-y)
Salles et al (29) R-CHOP (12 infusions/2 y)
386/382 48 mo 0.49 (0.39–0,62) 50% (4-y) 70% (4-y)
Press et al (38) R-CHOP Observation
265/267 4.9 y NA 76% (2-y) 80% (2-y)
CHOP
131I tositumomab
Abbreviations: CHOP, regimen of cyclophosphamide/doxorubicin/vincristine/prednisone CI, confidence interval; HR, hazard ratio; mo, months; NA, not available; PFS,
progression-free survival; R-CHOP, regimen of rituximab/cyclophosphamide/doxorubicin/vincristine/prednisone; R-CVP, regimen of rituximab/cyclophosphamide/
vincristine/prednisone; tx, treatment; y, year.
a
Before randomization.
b
Chemotherapy included anthracycline in 43% of patients and rituximab in 15%.
tumomab administered as single-agent therapy in 76
patients provided a high response rate (95%) and the 5-year
PFS was 59%. 35 Unfortunately, this approach was never
evaluated in a randomized study against other forms of
therapy. Two randomized studies (Table 3) addressed the
role of radioimmunotherapy as consolidation therapy in
patient responders to chemotherapy. In the FIT study, 36,37
administration of a single course of ibritumomab tiutexan
resulted in high rates of complete response (87.4% with
either complete or unconfirmed complete response) and
significant improvements in PFS (median 15 months in the
observation arm compared with 49 months in the experimental
arm). OS was not different between the two groups
but six myeloid malignancies were observed in patients that
had received radioimmunotherapy, compared with one in
the control arm (p � 0.0001). 37 The major pitfall of this
study was the fact that only 15% of patients had received
rituximab with induction chemotherapy. The results of the
SWOG0016 Intergroup study comparing R-CHOP (267 patients)
with CHOP followed by tositumomab (265 patients)
have been recently presented. 38 With a median follow-up of
4.9 years, 2-year PFS and OS were not significantly different
between the groups (80% and 93%, respectively, in the
radioimmunotherapy arm, 76% and 97%, respectively, in the
R-CHOP arm). A slight but nonsignificant excess of secondary
myeloid malignancies was observed in patients in the
radioimmunotherapy arm. 38
Based on these results, it is therefore difficult to establish
the role of radioimmunotherapy in the first-line treatment of
patients with follicular lymphoma. Studies assessing the
role of consolidation therapy with radiolabeled antibodies
against rituximab maintenance in the context of induction
chemotherapy with rituximab should be conducted.
Is There a Role for High-Dose Therapy Supported
with Stem Cell Transplantation?
Although this strategy was investigated before the rituximab
era with some indication of prolonged PFS in at least
two studies, 39 autologous stem cell transplantation does not
seem to improve OS. 40 This strategy therefore does not
represent a standard option as consolidation therapy for
patients with responsive disease in first-line settings.
Future Prospects for the Management of Indolent
Lymphoma in First-Line Therapy
Although the results achieved with the combination of
chemotherapy and maintenance or consolidation therapies
are favorable, with 5-year OS estimates exceeding 90%,
several questions remain. The first question regards the
stratification of patients, which is currently performed with
clinical criteria. It is our hope that new biologic tools will
translate recent advances in the understanding of the biology
of follicular lymphoma into clinical practice and provide
useful predictors of patient outcome that will help tailor
therapy. 41 A second question lies in the evaluation of treatment
efficacy and the benefit of achieving complete response
to first-line therapy. 42 To improve the accuracy of this
evaluation, minimal residual disease has not gained a wide
acceptance outside clinical trials given its technical limitations.
But recent studies underline the value of 18 Ffluorodeoxy-D-glucose
positron emission tomography in
deciphering the quality of response in patients that achieved
Fig 1. Outcome of patients randomly assigned to observation or rituximab maintenance therapy in the PRIMA trial according to the Follicular
Lymphoma Prognostic Index (FLIPI).
Abbreviations: PFS, progression free survival; NA, not applicable.
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