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Molecular Responses With Fludarabine, Mitoxantrone, and Dexamethasone Plus Rituximab Chemoimmunotherapy for Stage IV Indolent Follicular Non-Hodgkin’s Lymphoma

Molecular Responses With Fludarabine, Mitoxantrone, and Dexamethasone Plus Rituximab Chemoimmunotherapy for Stage IV Indolent Follicular Non-Hodgkin’s Lymphoma

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 administration):

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.

Click here to read Dr. Bruce Cheson's commentary on this abstract.

 
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