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Clinical Trial
. 2015 Nov;171(4):471-7.
doi: 10.1111/bjh.13607. Epub 2015 Jul 24.

Tamibarotene in patients with acute promyelocytic leukaemia relapsing after treatment with all-trans retinoic acid and arsenic trioxide

David Sanford  1 , Francesco Lo-Coco  2 , Miguel A Sanz  3   4 , Eros Di Bona  5 , Steven Coutre  6 , Jessica K Altman  7 , Meir Wetzler  8 , Steven L Allen  9 , Farhad Ravandi  1 , Hagop Kantarjian  1 , Jorge E Cortes  1
Affiliations
Clinical Trial

Tamibarotene in patients with acute promyelocytic leukaemia relapsing after treatment with all-trans retinoic acid and arsenic trioxide

David Sanford et al. Br J Haematol. 2015 Nov.

Abstract

Treatment of acute promyelocytic leukaemia (APL) with arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) is highly effective first-line therapy, although approximately 5-10% of patients relapse. Tamibarotene is a synthetic retinoid with activity in APL patients who relapse after chemotherapy and ATRA, but has not been studied in relapse after treatment with ATO and ATRA. We report on a phase II study of tamibarotene in adult patients with relapsed or refractory APL after treatment with ATRA and ATO (n = 14). Participants were treated with tamibarotene (6 mg/m(2) /d) during induction and for up to six cycles of consolidation. The overall response rate was 64% (n = 9), the rate of complete cytogenetic response was 43% (n = 6) and the rate of complete molecular response was 21% (n = 3). Relapse was frequent with 7 of 9 responders relapsing after a median of 4·6 months (range 1·6-26·8 months). The median event-free survival (EFS) was 3·5 months [95% confidence interval (CI) 0-8·6 months] and the median overall survival (OS) was 9·5 months (95% CI 5·9-13·1 months). These results demonstrate that tamibarotene has activity in relapsed APL after treatment with ATO and ATRA and further studies using tamibarotene as initial therapy and in combination with ATO are warranted.

Keywords: Acute promyelocytic leukaemia; all-trans retinoic acid; arsenic trioxide; clinical trial; tamibarotene.

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Figures

Fig 1
Fig 1
Event-free survival for the entire population of patients with relapsed/refractory acute promyelocytic leukaemia.
Fig 2
Fig 2
Overall survival for the entire population of patients with relapsed/refractory acute promyelocytic leukaemia.
See this image and copyright information in PMC

References

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