Addition of Rituximab to Chlorambucil Produces Superior Event-Free Survival in the Treatment of Patients With Extranodal Marginal-Zone B-Cell Lymphoma: 5-Year Analysis of the IELSG-19 Randomized Study.

Jan 2013

Zucca E, Conconi A, Laszlo D, López-Guillermo A, Bouabdallah R, Coiffier B, Sebban C, Jardin F, Vitolo U,Morschhauser F, Pileri SA, Copie-Bergman C, Campo E, Jack A, Floriani I, Johnson P, Martelli M, Cavalli F, Martinelli G,Thieblemont C.

Source

Emanuele Zucca and Franco Cavalli, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland; Annarita Conconi, Amedeo Avogadro University of Eastern Piedmont, Novara; Daniele Laszlo and Giovanni Martinelli, European Institute of Oncology; Irene Floriani, Pharmacological Research Institute, Milan; Umberto Vitolo, S. Giovanni Battista Hospital, Torino; Stefano A. Pileri, University of Bologna, Bologna; Maurizio Martelli, University "La Sapienza," Rome, Italy; Armando López-Guillermo and Elias Campo, Hospital Clinic, Barcelona, Spain; Reda Bouabdallah, Institut Paoli-Calmettes, Marseille; Bertrand Coiffier, Centre Hospitalier Lyon-Sud, Pierre-Benite; Catherine Sebban, Centre Léon Bérard, Lyon; Fabrice Jardin, Centre Henri Becquerel, Rouen; Franck Morschhauser, Hôpital Claude Huriez, Lille; Christiane Copie-Bergman, Assistance Publique-Hopitaux de Paris Groupe Henri Mondor-Albert Chenevier, L'Institut National de la Santé et de la Recherche Médicale (INSERM) U955, Créteil; Catherine Thieblemont INSERM Institut Universitaire d'Hématologie U728, Hopital Saint Louis, Paris, France; Andrew Jack, St. James's University Hospital, Leeds; and Peter Johnson, Southampton General Hospital, Southampton, United Kingdom.

Abstract

PURPOSE

Apart from localized gastric disease, there is no consensus on standard initial treatment of mucosa-associated lymphoid tissue lymphoma. The IELSG-19 study (Randomized Trial of Chlorambucil Versus Chlorambucil Plus Rituximab Versus Rituximab in MALT Lymphoma) was launched to compare chlorambucil alone versus chlorambucil plus rituximab in patients not previously given systemic anticancer therapy. 

PATIENTS AND METHODS

Patients not responding to or not suitable for local therapy were eligible. In arm A, chlorambucil was given daily 6 mg/m(2) orally (PO) for 6 weeks. Responding patients and those with stable disease continued to be given daily chlorambucil 6 mg/m(2) PO for 14 consecutive days every 28 days for four cycles. In arm B, intravenous rituximab 375 mg/m(2) per day was added on days 1, 8, 15, 22, 56, 84, 112, and 140. After completion of the planned accrual, the protocol was amended to introduce a third arm with rituximab alone. We report the planned final analysis of the first two arms (113 patients in arm A and 114 in arm B).

RESULTS

At a median follow-up of 62 months, the 5-year event-free survival (EFS) was significantly better for the patients treated in arm B (68% v 50%; P = .002) who, despite similar overall response rates (90% v 87%), achieved a higher complete remission rate (78% v 65%; P = .025). Progression-free survival was also improved but it did not reach statistical significance (P = .057). Five-year overall survival (OS) was 89% in both arms. Both treatments were well tolerated without unexpected toxicities. 

CONCLUSION

Both treatments were active; the better response rate and EFS obtained with the addition of rituximab did not translate into improved OS.

Full text:

Journal of Clinical Oncology