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Feasibility and Toxicity of Concomitant Radio/Immunotherapy with MabThera (Rituximab®) for Patients with Non-Hodkin's Lymphoma

Results of a Prospective Phase I/II Study

Durchführbarkeit und Toxizität einer kombinierten Radioimmuntherapie mit MabThera (Rituximab®) als neue Behandlungsoption für Patienten mit Non-Hodkin-Lymphomen – Ergebnisse einer prospektiven Phase-I/II-Studie

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Abstract

Purpose:

Non-Hodgkin's lymphomas (NHL) have a high radio- and chemosensitivity. Although initially responsive, approximately 50% of low grade B-cell lymphomas relapse after 10–15 years. Besides chemo- and radiotherapy, rituximab, a mouse/human chimeric antibody targeting CD20 antigen on the surface of B-cell lymphoma cells, is another treatment approach. In vitro data showed potentiation of radiation-induced apoptosis by addition of rituximab. The purpose of this study was to evaluate the feasibility and toxicity of radiotherapy with concomitant application of rituximab in NHL patients.

Patients and Methods:

A total of 21 patients with B-cell lymphoma (stage I: n = 11; II: n = 5; III: n = 1; IV: n = 4) were included in this study, treated with radiotherapy of 30–40 Gy and weekly application of rituximab (375 mg/m2). Nine patients had R-CHOP chemotherapy previously, 1 patient leuceran chemotherapy, and 2 patients an initial treatment with 6 cycles of rituximab. Mean time of follow-up was 41.7 months.

Results:

No grade 4 toxicity or treatment-related death was observed. In 1 patient, rituximab application had to be stopped after 3 cycles due to radiation-induced side effects. No late toxicities were reported. All patients were in complete remission after treatment. Progression or relapse was observed in 6 patients (28%); the mean time to progression was 27 months. The mean overall survival (OS) was 53 months.

Conclusion:

Combined radio/immunotherapy is feasible and safe. Treatment was well tolerated, no late toxicities were observed, and treatment outcome is promising. Randomized trials are necessary to clarify the benefit of this treatment approach and its applicability.

Zusammenfassung

Ziel:

Non-Hodgkin-Lymphome (NHL) haben eine hohe Chemo-/Radiosensitivität und zeigen zunächst ein sehr gutes Therapieansprechen. Allerdings rezidivieren ca. 50% der niedrigmalignen B-Zell-Lymphome nach 10–15 Jahren. Neben Chemo- und Radiotherapie stellt Rituximab eine berechtigte Therapieoption dar. In-vitro-Versuche konnten einen radiosensibilisierenden Effekt von Rituximab in Kombination mit Radiotherapie durch Verstärkung der strahleninduzierten Apoptose zeigen. Ziel dieser Pilotstudie war die Evaluierung von Durchführbarkeit und Toxizität einer Radiotherapie in Kombination mit dem monoklonalen Antikörper Rituximab.

Patienten und Methodik:

21 Patienten (pts) mit NHL (Stadium I: 11, II: 5, III: 1, IV: 4) wurden mit 30–40 Gy Radiotherapie und 1x wöchentlicher konkomittanter Applikation von Rituximab (375 mg/m2) behandelt. 9 pts erhielten davor Chemotherapie mit R-CHOP, 1 pts mit Leukeran, 2 pts wurden initial mit 6 Zyklen Rituximab behandelt. Mittleres Follow-up war 41,7 Monate.

Ergebnisse:

Keine Grad-4-Toxizität wurde beobachtet. Aufgrund radiogener Nebenwirkungen wurde in einem pts die Rituximab-Gabe nach 3 Zyklen abgebrochen. Keine Spättoxizitäten sind dokumentiert. Alle pts erreichten eine komplette Remission. Bei 6 pts (28%) ist es zu einer Progression oder einem Rezidiv gekommen. Mittleres Überleben war 53 Monate, mittlere Progressionszeit 27 Monate.

Schlussfolgerung:

Eine kombinierte Radioimmuntherapie ist gut durchführbar und hat in diesem Patientenkollektiv zu keiner verstärkten Toxizität geführt. Keine Spätnebenwirkungen wurden beobachtet, und die Behandlungsergebnisse sind vielversprechend. Randomisierte Studien sind notwendig, um Nutzen und Anwendbarkeit dieser kombinierten Therapie beim NHL zu prüfen.

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Authors and Affiliations

  1. Department of Radiotherapy/Radiooncology, Medical University Innsbruck, Innsbruck, Austria

    Alfred Haidenberger*, Bela-Andre Popper, Ira Skvortsova & Peter Lukas

  2. Institute of Radiology, Hospital Gmunden, Gmunden, Austria

    Sabine Fromm-Haidenberger*

  3. Department of Radiotherapy/Radiooncology, Hospital Feldkirch, Feldkirch, Austria

    Alexander de Vries

  4. Department of Hematology, Medical University Innsbruck, Innsbruck, Austria

    Michael Steurer, Johanna Kantner & Eberhard Gunsilius

  5. Institute of Medical Radiology, Hospital Gmunden, Miller v. Aichholzstr. 49, 4810, Gmunden, Austria

    Sabine Fromm-Haidenberger*

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  1. Alfred Haidenberger*
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  2. Sabine Fromm-Haidenberger*
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  3. Alexander de Vries
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  4. Bela-Andre Popper
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  6. Ira Skvortsova
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  9. Peter Lukas
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Correspondence to Sabine Fromm-Haidenberger*.

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*Both authors contributed equally to this work.

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Haidenberger*, A., Fromm-Haidenberger*, S., de Vries, A. et al. Feasibility and Toxicity of Concomitant Radio/Immunotherapy with MabThera (Rituximab®) for Patients with Non-Hodkin's Lymphoma. Strahlenther Onkol 187, 300–305 (2011). https://doi.org/10.1007/s00066-011-2169-y

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