Long-term survival of patients with mantle cell lymphoma after autologous haematopoietic stem-cell transplantation in first remission: a post-hoc analysis of an open-label, multicentre, randomised, phase 3 trial.

BACKGROUND

Autologous haematopoietic stem-cell transplantation (HSCT) in first remission is the current standard treatment in fit patients with mantle cell lymphoma. In this long-term follow-up study, we aimed to evaluate the efficacy of autologous HSCT versus interferon alfa maintenance after chemotherapy without or with rituximab in patients with primary advanced-stage mantle cell lymphoma.

METHODS

We did a post-hoc, long-term analysis of an open-label, multicentre, randomised, phase 3 trial done in 121 participating hospitals or practices across six European countries. Patients who were aged 18-65 years with previously untreated stage III-IV mantle cell lymphoma and an ECOG performance score of 0-2 were eligible for participation. Patients were randomly assigned (1:1) to receive either myeloablative radiochemotherapy (fractionated total body irradiation with 12 Gy/day 6-4 days before autologous HSCT and cyclophosphamide 60 mg/kg per day intravenously 3-2 days before autologous HSCT) followed by autologous HSCT (the autologous HSCT group) or interferon alfa maintenance (the interferon alfa maintenance group; 6 × 10

FINDINGS

Between Sept 30, 1996, and July 1, 2004, 269 patients were randomly assigned to receive either autologous HSCT or interferon alfa maintenance therapy. The median follow-up was 14 years (IQR 10-16), with the intention-to-treat population consisting of 174 patients (93 [53%] in the autologous HSCT group and 81 [47%] in the interferon alfa maintenance group) who responded to induction therapy. The median age was 55 years (IQR 47-60), and R-CHOP was used in 68 (39%) of 174 patients. The median progression-free survival was 3·3 years (95% CI 2·5-4·3) in the autologous HSCT group versus 1·5 years (1·2-2·0) in the interferon alfa maintenance group (log-rank p<0·0001; aHR 0·50 [95% CI 0·36-0·69]). The median overall survival was 7·5 years (95% CI 5·7-12·0) in the autologous HSCT group versus 4·8 years (4·0-6·6) in the interferon alfa maintenance group (log-rank p=0·019; aHR 0·66 [95% CI 0·46-0·95]). For patients treated without rituximab, the progression-free survival adjusted HR for autologous HSCT versus interferon alfa was 0·40 (0·26-0·61), in comparison to 0·72 (0·42-1·24) for patients treated with rituximab. For overall survival, the adjusted hazard ratio for HSCT versus interferon alfa was 0·52 (0·33-0·82) without rituximab and 1·05 (0·55-1·99) for patients who received rituximab.

INTERPRETATION

Our results confirm the long-term efficacy of autologous HSCT to treat mantle cell lymphoma established in the pre-rituximab era. The suggested reduced efficacy after immunochemotherapy supports the need for its re-evaluation now that antibody maintenance, high-dose cytarabine, and targeted treatments have changed the standard of care for patients with mantle cell lymphoma.

FUNDING

Deutsche Krebshilfe, the European Community, and the Bundesministerium für Bildung und Forschung, Kompetenznetz Maligne Lymphome.

Informations de copyright

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Déclaration de conflit d'intérêts

Declaration of interests A-KZ declares that this work was done before her employment at Janssen-Cilag. Opinions expressed are solely her own and do not express the views or opinions of her employer. A-KZ has received stock or stock options from Johnson & Johnson. KH has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Roche, Celgene, Servier, Sanofi, EUSA Pharma, and Hexal; has received support for attending meetings or travel, or both, from Roche, Celgene, and Sanofi; and has participated on a data safety monitoring board or advisory board from Roche, Celgene, Servier, EUSA Pharma, and Gilead. MT has received consultancy fees and research funding from Amgen, Roche, Regeneron, Kite, and Macrogenics. CS has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Bristol Myers Squibb, Janssen, and Norvatis; and support for attending meetings or travel, or both, from Bristol Myers Squibb, Roche, Novartis, and Kite Gilead. GL has received grants or contracts from AQUINOX, AGIOS, AstraZeneca, Bayer, Gilead, Janssen, Morphosys, Roche, and Verastem (grant to institution); consulting fees from Roche, Gilead, Janssen, Bayer, Bristol Myers Squibb/Celgene, Novartis, AstraZeneca, Takeda, NanoString, AbbVie, Incyte, Morphosys, Genmab, and Karyopharm; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Roche, Gilead, Janssen, Bayer, Bristol Myers Squibb/Celgene, Novartis, AstraZeneca, AbbVie and Incyte; payment for expert testimony from Morphosys; support for attending meetings or travel, or both, from Roche, Janssen, and Bristol Myers Squibb/Celgene; and participated on a data safety monitoring board or advisory board from Roche, Gilead, Janssen, Bayer, Bristol Myers Squibb/Celgene, Novartis, AstraZeneca, Takeda, Nanostring, Oncopeptides, AbbVie, Incyte, Morphosys, Genmab, and Karyopharm. JD has received personal fees from Janssen, Roche, AbbVie, Celgene, Takeda, and AstraZeneca. VV has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Janssen; support for attending meetings or travel, or both, from Amgen and AbbVie; and participated on a data safety monitoring board or advisory board from Beigene, Gilead, and Bristol Myers Squibb. WK has received report grants from Roche, Amgen, Takeda, and Regeneron. WH has received support for the present manuscript in research funding from Roche. MD has received institutional research grants by AbbVie, Bayer, Celgene, Janssen, and Roche; honoraria for scientific advisory boards from AstraZeneca, Bayer, Beigene, Celgene, Genmab, Gilead, Incyte, Janssen, Novartis, and Roche; and speaker's honoraria from Amgen, AstraZeneca, Bayer, Celgene, Gilead, Janssen, and Roche. EH has received travel support for attending meetings or travel, or both, from Roche. All other authors declare no competing interests.