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Evaluating treatment strategies in advanced Waldenström macroglobulinemia: use of quality-adjusted survival analysis

Leukemia volume 15, pages 1466–1470 (2001)Cite this article

Abstract

A randomized phase II multicenter clinical trial comparing the efficacy of fludarabine (FAMP) to that of the association of cyclophosphamide, doxorubicin and prednisone (CAP) in 92 patients with Waldenström's macroglobulinemia in first relapse or with primarily resistant disease, was conducted on the behalf of the ‘Groupe Coopératif Macroglobulinémie’. The main analysis of this study failed to demonstrate a clear cut benefit of FAMP in terms of overall survival (OS), although a significant benefit in terms of time to disease progression and event-free survival (EFS) was noted. In this rare disorder, where few randomized trials have been conducted, we took advantage of this trial to assess treatment differences while integrating quality of life considerations. We thus performed a quality-adjusted survival analysis, using the quality-adjusted time without symptoms or toxicity (Q-TWiST) approach. Four health states differing in terms of quality of life (QoL) were defined, namely treatment-related toxicity, treatment free of toxicity, no treatment or symptoms, and relapse. The average time spent in these health states (TOX, CT, TWiST and REL, respectively) were then weighted by utility coefficients reflecting relative QoL value according to that of TWiST and summed up giving the so-called Q-TWiST. No difference was found between randomized groups in terms of mean CT. Mean TOX in the two groups were similarly close except when considering alopecia as a relevant toxic event. By contrast, mean TWiST was 5.9 months longer in the FAMP group than in the CAP group (P = 0.006). Unsurprisingly, given the absence of difference in OS but the difference in EFS in favor of the FAMP group, mean REL was increased by 6.8 months in the CAP group (P = 0.047). As a result, benefit of FAMP in terms of average Q-TWiST only relied on the value of the utility coefficient attributed to REL (UREL), with a significant benefit when UREL ranged from 0 to 0.28, ie in patients undergoing poor QoL after relapse, which is likely.

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Acknowledgements

We acknowledge all the participants of the ‘French Cooperative group on CLL and Macroglobulinemia’ and Schering SA France for making this research possible. We also thank Mr Hervé Finel for technical assistance. This work was supported by a grant of the Association pour la Recherche sur le Cancer (ARC) No. 6531.

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Author notes

  1. V Lévy and R Porcher: These two authors participated equally in the study

Authors and Affiliations

  1. Département de Biostatistique et Informatique Médicale, Hôpital Saint Louis, Paris, France

    V Lévy, R Porcher & S Chevret

  2. U444 INSERM, Paris, France

    V Lévy, R Porcher & S Chevret

  3. Service d'Hématologie, Hôpital Pitié Salpêtrière, Paris, France

    V Leblond

  4. Service d'Immmuno-Hématologie, Hôpital Saint Louis, Paris, France

    JP Fermand

  5. Service des Maladies du Sang, Hôpital Claude Huriez, Centre Hospitalier Régional Universitaire, Lille, France

    B Cazin

  6. Service d'Hématologie, Hôpital Hautepierre, Centre Hospitalier Régional Universitaire, Strasbourg, France

    F Maloisel

  7. Service d'Hématologie, Hôtel-Dieu, Centre Hospitalier Universitaire, Nantes, France

    JL Harousseau

  8. Service d'Hématologie, Centre Hospitalier Universitaire, Limoges, France

    L Remenieras

  9. Laboratoire Schering SA, Lys-les-Lannoy, France

    O Guibon

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on behalf of the French Cooperative group on CLL and Macroglobulinemia

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Lévy, V., Porcher, R., Leblond, V. et al. Evaluating treatment strategies in advanced Waldenström macroglobulinemia: use of quality-adjusted survival analysis. Leukemia 15, 1466–1470 (2001). https://doi.org/10.1038/sj.leu.2402221

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