Stage IV indolent lymphomas are currently considered incurable
disorders. However, the achievement of an early molecular remission, as
determined by the bcl-2 polymerase chain reaction (PCR) assay, is associated
with a better outcome. In view of its excellent correlation with failure-free
survival, the PCR technique has the potential of providing a tumor marker that
can be used as an early surrogate end point.
In the search for a treatment that could result in a higher
molecular response rate, we designed a study that combines eight courses of FND
(fludarabine [Fludara], mitoxantrone [Novantrone], dexamethasone [J Clin Oncol
14:1262, 1996]) plus the monoclonal antibody rituximab (Rituxan). One of the
aims was to determine which schedule of rituximab/chemotherapy is superior. We
randomized between the potentially synergistic concurrent antibody/chemotherapy
combination vs delayed administration of antibody (which takes advantage of the
recovery of immune function at the time of rituximab administration).
We have entered 134 previously untreated patients with stage IV
indolent non-Hodgkin’s lymphoma (NHL) to either concurrent rituximab + FND
(rituximab given on day 1 of the first six FND courses) or to delayed FND ®
rituximab (FND first, followed by rituximab ´ 6
starting 12 months later). All patients received interferon ´
1 year. After eight courses of FND we have baseline PCR data on 95 follicular
NHL patients, 70 of which (74%) had bcl-2 rearrangement in peripheral blood (PB)
and bone marrow (BM). Median follow-up is 12 months. Of the 70 patients at
baseline, PCR data are currently available after 6 months of treatment in 39 PB
and 32 BM, and at 12 months in 27 and 23, respectively. The data are shown in
the table below (6- and 12-month data in the delayed arm are before rituximab
CONCLUSION: At 6 months a higher molecular response in PB was
seen in the concurrent rituximab + FND arm; the same trend was seen in BM, but
at 12 and 18 months the molecular response rate was equivalent for both arms.
The projected failure-free survival (FFS) rate at 24 months is 88% for PB
molecular responders at 6 months vs 34% for nonresponders (P = .05). At
this point there is no significant difference in FFS between the two arms of the
study, although the trend favors the concurrent arm.