Buske.qxp 31/10/08 12:25 Page 43
Consolidation Therapy for Follicular Lymphoma
patients with advanced FL after induction of response with chemotherapy with fludarabine followed six to eight weeks later
rituximab–chemotherapy combination compared with no maintenance with tositumomab/
131
I-tositumomab. After the fludarabine course,
therapy. The results from this international open-label, multicentre, 89% of 35 patients and 9% of 31 patients achieved CR. Following
randomised study are expected in 2009.
131
I-tositumomab consolidation therapy, all 35 patients responded
and 86% achieved CR.
37
Consolidation Therapy for Follicular Lymphoma
The aim of consolidation therapy is to further improve the quality of A preliminary study evaluated
90
Y-ibritumomab tiuxetan following
response, preferably with the eradication of minimal residual disease CHOP–rituximab. After CHOP–rituximab, the CR rate was 28%. After
(MRD) after successful cytoreduction by chemotherapy. Myeloablative RIT, the CR rate was 67%.
38
Two-year PFS was 85%. A phase II study
therapy before ASCT and RIT are two potential consolidation investigating the efficacy of fludarabine and mitoxantrone (FM)
strategies that have been investigated in the clinical setting as both chemotherapy followed by
90
Y-ibritumomab tiuxetan in patients with
stage III or IV untreated indolent FL showed an ORR of 98% and a CR
rate of 71% after FM chemotherapy. Of the patients who completed
the sequential treatment (chemotherapy plus RIT), 97% achieved
Radioimmunotherapy is a promising
CR.
39
At a median follow-up of 30 months, the estimated three-year
PFS rate was 76%, and the three-year OS rate was estimated to
approach for consolidation therapy in
be 100%.
patients with follicular lymphoma.
Recently, the results of the first phase III trial evaluating RIT
consolidation treatment were presented. The phase III First-line
Indolent Trial (FIT) evaluated the efficacy and safety of
first- and second-line therapy. Consolidation therapy with rituximab as
90
Y-ibritumomab tiuxetan consolidation in patients with advanced FL
a single agent delivered short-term has not been established for either responding to first-line chemotherapy.
40
The multicentre study tested
FL or aggressive lymphoma. As opposed to myelablative therapy whether a single infusion of
90
Y-ibritumomab tiuxetan would prolong
followed by ASCT or RIT, which both take around 14 days, rituximab PFS in patients responding to initial cytoreduction.
maintenance treatment continues over a period of two years.
Major inclusion criteria were: CD20-positive grade 1 or 2 FL, stage III
Radioimmunotherapy or IV at diagnosis, normal peripheral blood cell counts, <25% bone
RIT is a treatment modality that combines the specificity of monoclonal marrow involvement, age ≥18 years and CR/CRu or PR after first-line
antibodies against tumour antigens with therapeutic radioisotopes chemotherapy determined by physical examination, CT scans and
delivered to sites of disseminated disease. Encouraging results have bone marrow biopsy. After completing induction therapy that
been reported for the
90
Y-labelled IgG
1
κ anti-CD20 antibody included various regimens, patients were randomised to receive either
ibritumomab tiuxetan and also for the
131
I-labelled IgG
90
2
κ anti-CD20 Y-ibritumomab tiuxetan (208 patients) or no further treatment
antibody tositumomab in the treatment of FL. Currently, only (206 patients).
90
Y-ibritumomab tiuxetan is approved for use in Europe as
single-agent therapy in patients with relapsed follicular lymphoma For patient subgroups in PR or CR after induction, median PFS was
who have been treated with rituximab. It was recently approved for 6.3 versus 29.7 months (p<0.0001) and 29.9 versus 54.6 months
consolidation therapy after remission induction in previously untreated (p=0.01), respectively, in favour of
90
Y-ibritumomab tiuxetan treatment.
patients with follicular lymphoma. In the non-myeloablative approach, After
90
Y-ibritumomab tiuxetan consolidation, 77% of patients in
both agents have demonstrated comparable activity, with response PR after induction therapy converted to CR; in total, 87% of patients
rates of 60–80% and CR/CRu rates of between 4 and 15%, including
patients who relapsed after or were refractory to previous
chemotherapy and rituximab.
35
Further prospective studies are needed
Radioimmunotherapy as Consolidation Therapy
to confirm the potential benefits of
Studies evaluating RIT as consolidation therapy have shown promising
data. A phase II trial of CHOP followed by tositumomab/
radioimmunotherapy, particularly
131
I-tositumomab for previously untreated FL in 90 eligible patients
following rituximab chemotherapy.
with previously untreated advanced-stage FL reported an OR of
91%, with a 69% CR rate. The estimated five-year OS rate was 87%,
and the PFS rate was 67%.
were in CR/CRu, 76% in CR and 11% in CRu. Toxicity encompassed
These data were superior to corresponding figures for patients primarily haematological effects. Median platelet count nadir was at
treated on previous Southwest Oncology Group protocols with CHOP 45x10
9
/l approximately five weeks post-
90
Y-ibritumomab tiuxetan, and
alone.
36
Interestingly, 21% of patients with FLIPI high-risk features the median neutrophil nadir was 1.0x10
9
/l almost six weeks post-RIT.
had worse OS than lower-risk patients (p=0.05), although no Grade 3/4 infections occurred in 8% in the
90
Y-ibritumomab tiuxetan
differences were reported in PFS between FLIPI-stratified groups. arm versus 2% in the control arm. This is the first phase III study to
Another phase II study evaluated the efficacy of abbreviated convincingly show a benefit with RIT in the consolidation setting.
EUROPEAN ONCOLOGY 43
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