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Results of a phase II study of vorinostat in combination with intravenous fludarabine, mitoxantrone, and dexamethasone in patients with relapsed or refractory mantle cell lymphoma: an interim analysis

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Abstract

Purpose

Mantle cell lymphoma (MCL) is a disease that frequently relapses and primarily affects elderly people. We performed an open-label, multi-center, phase II study to investigate the effect and quality of life (QoL) of treatment with vorinostat in combination with fludarabine, mitoxantrone and dexamethasone (V-FND) for relapsed or refractory MCL.

Methods

The treatment schedule was composed of four cycles of induction treatment with V-FND and subsequent consolidation therapy involving autologous hematopoietic stem cell transplantation or six cycles of vorinostat maintenance. QoL was assessed using EORTC Core Quality of Life questionnaire (EORTC QLQ-C30) every 2 cycles.

Results

Data from a total of 20 patients were collected for an interim analysis. The median age was 67 years (range 49–75), and 14 or the patients (70 %) were male. The full course of V-FND induction treatment was completed in 11 patients, but only three completed all six cycles of maintenance therapy. Response to V-FND was not available in two patients. Among the other 18 patients, the objective response rate was 77.8 % (complete response in five patients + partial response in nine patients). Median progression-free survival was 9.3 months [95 % confidence interval (CI) 4.0–12.3]. Fifteen patients (75 %) experienced grade 3/4 toxicities. Analysis of QoL demonstrated significant deterioration of social functioning (p = 0.01), and significant aggravation of fatigue and nausea/vomiting (p = 0.04 and 0.01, respectively) after two cycles of V-FND induction.

Conclusions

V-FND is effective in patients with relapsed or refractory MCL. However, significant toxicities were hurdles to sustained V-FND therapy.

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Acknowledgments

We thank the patients and their families who took part in this study, the coordinators and the investigators. This work is supported in part by a research grant from investigator-initiated studies program of Merck Sharp & Dohme Corp. The opinions expressed in this paper are those of the authors and do not necessarily represent those of Merck Sharp & Dohme Corp.

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Authors and Affiliations

  1. Department of Internal Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea

    Dong-Yeop Shin

  2. Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-gu, Seoul, 135-710, Republic of Korea

    Seok Jin Kim & Won Seog Kim

  3. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Ulsan, Republic of Korea

    Dok Hyun Yoon

  4. Department of Internal Medicine, Korea University College of Medical College, Seoul, Republic of Korea

    Yong Park

  5. Department of Internal Medicine, Wonju Severance Christian Hospital, Yonsei University College of Medicine, Wonju, Republic of Korea

    Jee Hyun Kong

  6. Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

    Jeong-A Kim

  7. Department of Internal Medicine, Daegu Fatima Hospital, Daegu, Republic of Korea

    Byung-Su Kim

  8. Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, Hallym University College of Medicine, Chuncheon, Republic of Korea

    Hyo Jung Kim

  9. Department of Internal Medicine, Soonchunhyang University Hospital, Soonchunhyang University College of Medicine, Seoul, Republic of Korea

    Jong-Ho Won

  10. Department of Internal Medicine, Soonchunhyang University Medical College, Bucheon, Republic of Korea

    Sung-Kyu Park

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  1. Dong-Yeop Shin
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Won Seog Kim received a research grant from Merck Sharp & Dohme Corp. The other authors declare that they have no conflict of interest.

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Shin, DY., Kim, S.J., Yoon, D.H. et al. Results of a phase II study of vorinostat in combination with intravenous fludarabine, mitoxantrone, and dexamethasone in patients with relapsed or refractory mantle cell lymphoma: an interim analysis. Cancer Chemother Pharmacol 77, 865–873 (2016). https://doi.org/10.1007/s00280-016-3005-y

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