Rituximab zur Remissionsinduktion bei rezidivierten und refraktären indolenten Lymphomen und Mantelzell-Lymphomen

 

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Hintergrund und Fragestellung: Eine Monotherapie mit Rituximab ist bei rezidivierten follikulären Lymphomen wirksam. Phase-II-Studien zeigten bei einer Kombination mit Chemotherapie eine wesentliche Verbesserung der Remissionsraten. Bislang gab es hierzu jedoch keine prospektiv randomisierten Studien.

Patienten und Methoden: 1998 wurde die multizentrische Phase-III-Studie der GLSG begonnen. Eingeschlossen waren Patienten mit rezidiviertem oder refraktärem indolentem Lymphom oder Mante^lzell-Lymphom (MCL). Zur Rezidivbehandlung wurde folgende Kombination gewählt: Fludarabin 25 mg/m²/d, Tag 1-3, Cyclophosphamid 200 mg/m²/d, Tag 1-3 und Mitoxantron 8 mg/m²/d an Tag 1 (FCM). Insgesamt wurden vier Zyklen im Abstand von 4 Wochen verabreicht. Die Patienten wurden prospektiv für eine alleinige Therapie mit FCM versus Immunochemotherapie mit R-FCM (375 mg/m² einen Tag vor FCM) randomisiert.

Ergebnisse: Von den 147 Patienten hatten 93 ein follikuläres Lymphom (FL), 40 Patienten ein MCL und 14 Patienten ein lymphoplasmozytisches/-zytoides Lymphom. Eine Zwischenauswertung von 94 evaluierbaren Patienten ergab mit dem sequentiellen Test einen signifikanten Vorteil für den R-FCM-Arm. Hier lag die Ansprechrate bei 83 % gegenüber 58% nach alleiniger Chemotherapie mit 35 % respektive 13 % kompletten Remissionen. Ein ähnlicher Vorteil zeigte sich in der Auswertung der einzelnen Subentitäten, besonders deutlich für die MCL (Ansprechraten: 65 % vs. 33 %). In beiden Therapiearmen traten hämatologische Toxizitäten Grad 3 und 4 auf; infektiöse Komplikationen waren selten und in beiden Gruppen gleichmäßig verteilt.

Folgerungen: Bezogen auf das Gesamtansprechen zeigt diese prospektiv randomisierte Studie erstmals einen signifikanten Vorteil einer kombinierten Immunochemotherapie bei Patienten mit rezidiviertem oder refraktärem indolentem Lymphom auf.

Background and objective: Rituximab has shown a high activity in relapsed follicular lymphomas when given alone. Further on, phase-II-studies indicate that its addition to chemotherapy may improve the response rate substantially. However, so far, prospective randomized studies have not been available.

Patients and methods: In 1998 the GLSG started a multicenter trial in patients with relapsed or refractory indolent lymphoma or mantle cell lymphoma. A fludarabine-containing regimen (FCM) was chosen for salvage therapy, with fludarabine 25 mg/m²/d 1-3, cyclophosphamide 200 mg/m² d 1-3 and mitoxantrone 8 mg/m² d 1. A total of four courses, every 4 weeks were given. Patients were prospectively randomized for FCM alone or the immunochemotherapy with R-FCM (375 mg/m² one day before FCM)

Results: About 147 randomized patients 93 had follicular, 40 mantle cell and 14 lymphoplasmocytic/-cytoid lymphoma. Statistical analysis was performed by sequential testing and indicated for 94 fully evaluable patients a significant advantage for the R-FCM-arm, with an overall response rate of 83 % as compared to 58%, when treated with FCM alone (CR: 35 % vs. 13 %). Similar improvements of remission rate were detected in the different lymphoma subgroups, especially in MCL (OR: 65 % vs. 33 %). Both treatment options were associated with hematological toxicities of grade III and IV, but well tolerated; infectious complications were rare, with no difference between the two treatment groups.

Conclusion: This prospectively randomized trial demonstrates for the first time a significant improvement of the combined immunochemotherapy related to the remission rate in patients with relapsed or refractory indolent lymphoma.

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Dr. Roswitha Forstpointner

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