DOUBLING TIME AFTER FIRST ATTEMPT OF IMATINIB DISCONTINUATION IS HELPFUL TO IDENTIFY THE BEST CANDIDATE FOR THE SECOND ATTEMPT FOR TREATMENT-FREE REMISSION WITH DASATINIB: CANADIAN TRAD TRIAL
Author(s): ,
Dennis Kim
Affiliations:
Department of Medical Oncology & Hematology,PRINCESS MARGARET CANCER CENTRE,Toronto,Canada
,
Lambert Busque
Affiliations:
Hematopoiesis and Aging Research Unit,Hôpital Maisonneuve-Rosemont,Montreal,Canada
,
Donna Forrest
Affiliations:
Division of Hematology,Vancouver General Hospital,Vancouver,Canada
,
Lynn Savoie
Affiliations:
Department of Medical Oncology & Hematology,Tom Baker Cancer Centre,Calgary,Canada
,
Isabelle Bence-Bruckler
Affiliations:
Medicine,Ottawa Hospital Research Institute,Ottawa,Canada
,
Stephen Couban
Affiliations:
Division of Hematology,Queen Elizabeth II Health Sciences Centre,Halifax,Canada
,
Robert Delage
Affiliations:
Hôpital de l'Enfant-Jésus,Quebec,Canada
,
Anargyros Xenocostas
Affiliations:
Division of Hematology,London Health Sciences Centre,London,Canada
,
Elena Liew
Affiliations:
Department of Medicine,University of Alberta,Edmonton,Canada
,
Kristjan Paulson
Affiliations:
CancerCare Manitoba,Winnipeg,Canada
,
Pierre Laneuville
Affiliations:
Division of Hematology,McGill University Health Centre,Montreal,Canada
,
Jeffrey Lipton
Affiliations:
Department of Medical Oncology & Hematology,Princess Margaret Cancer Centre,Toronto,Canada
,
Suzanne Kamel-Reid
Affiliations:
Department of Pathology,Toronto General Hospital,Toronto,Canada
Brian Leber
Affiliations:
Department of Oncology,McMaster University,Hamilton,Canada
EHA Library. KIM D. Jun 14, 2019; 266210; PF410
Prof. Dennis KIM
Prof. Dennis KIM
Contributions
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Abstract

Abstract: PF410

Type: Poster Presentation

Presentation during EHA24: On Friday, June 14, 2019 from 17:30 - 19:00

Location: Poster area

Background

Canadian tyrosine kinase inhibitor (TKI) discontinuation trial is currently ongoing to answer the question if a 2nd generation TKI (2G-TKI), i.e. dasatinib (DA), should be used for retreatment for 2nd attempt of treatment-free remission (TFR2) after failing the first TFR attempt (TFR1) with imatinib (IM) discontinuation.

Aims

In our previous report (ASH 2018), the estimated TFR2 rate was 21.5% at 6 months. Also, rapid relapsing pattern after IM discontinuation correlated with a higher failure after DA discontinuation. It prompted us to revisit evaluating the correlation of doubling time (DT) after TFR1 attempt with TFR2 rate.

Methods

This prospective clinical trial (BMS CA180-543, Clinicaltrial.gov NCT#02268370) has 3 phases: 1) IM discontinuation phase, 2) DA rechallenge phase, 3) DA discontinuation phase. DA 100mg once daily was started if loss of molecular response is confirmed. DA is discontinued 12 months after achieving > MR4 for a 2nd TFR attempt. The study was designed to reject our null hypothesis if > 28% of pts (15 out of 54 pts) remain in TFR2 after DA discontinuation.

Doubling time (DT) has been calculated based on the BCR-ABL1 qPCR value taken monthly in the first 6 months after IM discontinuation. The baseline qPCR level prior to IM discontinuation was referenced. We decided to apply DT measured at 2 months after TFR1 attempt for further analysis based on the previous result (EHA 2018).

Results

As of Feb 21, 2019, 42 (32.%) of 131 pts are still ongoing. Of the 57 pts who lost molecular response after TFR1 attempt, 55 pts (96%) received DA and reachieved molecular response. 28/55 pts (51%) receiving DA attained MR4.5 for 12 months or longer, and discontinued it for TFR2. 21/28 (75%) of these pts lost molecular response at 3.7 months after TFR2 attempt. TFR2 rate was 20.2% at 6 months (7.4-37.5%), thus not allowing to reject our null hypothesis. 7 pts are still on DA discontinuation phase without losing molecular response (range 27-607 days).

In the risk factor analyses for TFR2, following variables were analyzed but did not show any association with TFR2: Sokal risk score (p=0.599), total IM duration prior to TFR1 attempt (p=0.09), MR4 duration with IM (p=0.866), or time to MR4 achievement with IM (p=0.09).However, shorter time to molecular relapse after TFR1 attempt (p=0.001, HR 0.523 per month, [0.350-0.782]) and rapid molecular relapse after TFR1 attempt (HR 4.003 for MMR loss, [1.397-11.48]) were confirmed to correlate with TFR2 failure.

Next, we have evaluated the DT at 2 months after TFR1 attempt. In the group with DT ≤zero (n=7), TFR2 rate was 50.0% at 6 months. It was 16.7% in those with DT ≥ 14 days (n=7), while it was 7.9% in those with DT < 14 days (n=15; p=0.04).

TFR2 rate at 6 months was significantly higher at 33.3% in low risk (i.e. those with DT ≤zero or ≥ 14 days, n=14) vs 7.9% in the high risk (i.e. those with DT<14 days, n=15; p=0.01, HR 2.902, [1.199-7.026]). The TFR2 rate in the low risk group (i.e. 33.3%) is above our pre-determined criteria to reject our null hypothesis (i.e. 28%), suggesting that this group can be a good candidate for TFR2 attempt.

Conclusion

1) Our result suggests that switch to 2G-TKI after failing TFR1 attempt may not improve TFR2 rate.

2) However, seeing a DT at 2 months after TFR1 attempt seems helpful to identify the subgroup having more benefit from the switch to 2G-TKI for TFR2 attempt.

Session topic: 8. Chronic myeloid leukemia - Clinical

Keyword(s): Chronic myeloid leukemia, Tyrosine kinase inhibitor

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