TY - JOUR
T1 - Durable treatment-free remission in patients with chronic myeloid leukemia in chronic phase following frontline nilotinib: 96-week update of the ENESTfreedom study.
AU - Ross, David
AU - Masszi, Tamas
AU - Casares, Maria Teresa
AU - Hellmann, Andrzej
AU - Stentoft, Jesper
AU - Conneally, Eibhlin
AU - Garcia-Gutierrez, Valentin
AU - Gattermann, Norbert
AU - Le Coutre, Philipp
AU - Martino, Bruno
AU - Saussele, Susanne
AU - Giles, Francis
AU - Radich, Jerald
AU - Saglio, Guiseppe
AU - Deng, Weiping
AU - Krunic, Nancy
AU - Bedoucha, Veronique
AU - Gopalakrishna, Prashanth
AU - Hochhaus, Andreas
PY - 2018/5/1
Y1 - 2018/5/1
N2 - Purpose: ENESTfreedom is evaluating treatment-free remission (TFR) following frontline nilotinib in patients with chronic myeloid leukemia (CML) in chronic phase. Following our primary analysis at 48 weeks, we here provide an updated 96-week analysis. Methods: Attempting TFR required ≥ 3 years of nilotinib, a molecular response of MR4.5 [BCR-ABL1 ≤ 0.0032% on the International Scale (BCR-ABL1IS)], and sustained deep molecular response (DMR) during a 1-year consolidation phase. Patients restarted nilotinib following loss of major molecular response (MMR; BCR-ABL1IS ≤ 0.1%). Results: Ninety-six weeks after stopping treatment (3.6-year median prior nilotinib duration), 93 of 190 patients (48.9%) remained in TFR. Of 88 patients who restarted nilotinib following loss of MMR, 87 regained MMR and 81 regained MR4.5 by the data cut-off. Ninety-six-week TFR rates were 61.3, 50.0, and 28.6% in patients with low, intermediate, and high Sokal risk scores at diagnosis, respectively. Patients consistently in MR4.5 during consolidation had higher TFR rates (50.6%) than patients with ≥ 1 assessment without MR4.5 during consolidation (35.0%). In a landmark analysis, 96-week TFR rates for patients with MR4.5, MR4 (BCR-ABL1IS ≤ 0.01%) but not MR4.5, and MMR but not MR4 at TFR week 12 were 82.6, 23.1, and 0%, respectively. There were no reports of disease progression or death due to CML; overall adverse event frequency decreased following TFR. Within the follow-up period, TFR did not adversely affect disease outcomes. Conclusions: These results demonstrate the feasibility and durability of TFR following frontline nilotinib and emphasize the importance of sustained DMR for TFR.
AB - Purpose: ENESTfreedom is evaluating treatment-free remission (TFR) following frontline nilotinib in patients with chronic myeloid leukemia (CML) in chronic phase. Following our primary analysis at 48 weeks, we here provide an updated 96-week analysis. Methods: Attempting TFR required ≥ 3 years of nilotinib, a molecular response of MR4.5 [BCR-ABL1 ≤ 0.0032% on the International Scale (BCR-ABL1IS)], and sustained deep molecular response (DMR) during a 1-year consolidation phase. Patients restarted nilotinib following loss of major molecular response (MMR; BCR-ABL1IS ≤ 0.1%). Results: Ninety-six weeks after stopping treatment (3.6-year median prior nilotinib duration), 93 of 190 patients (48.9%) remained in TFR. Of 88 patients who restarted nilotinib following loss of MMR, 87 regained MMR and 81 regained MR4.5 by the data cut-off. Ninety-six-week TFR rates were 61.3, 50.0, and 28.6% in patients with low, intermediate, and high Sokal risk scores at diagnosis, respectively. Patients consistently in MR4.5 during consolidation had higher TFR rates (50.6%) than patients with ≥ 1 assessment without MR4.5 during consolidation (35.0%). In a landmark analysis, 96-week TFR rates for patients with MR4.5, MR4 (BCR-ABL1IS ≤ 0.01%) but not MR4.5, and MMR but not MR4 at TFR week 12 were 82.6, 23.1, and 0%, respectively. There were no reports of disease progression or death due to CML; overall adverse event frequency decreased following TFR. Within the follow-up period, TFR did not adversely affect disease outcomes. Conclusions: These results demonstrate the feasibility and durability of TFR following frontline nilotinib and emphasize the importance of sustained DMR for TFR.
KW - Chronic myeloid leukemia
KW - Clinical trial
KW - Frontline
KW - Nilotinib
KW - Predictors of TFR
KW - Treatment-free remission
UR - http://www.scopus.com/inward/record.url?scp=85042212112&partnerID=8YFLogxK
U2 - 10.1007/s00432-018-2604-x
DO - 10.1007/s00432-018-2604-x
M3 - Article
VL - 144
SP - 945
EP - 954
JO - JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
JF - JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
SN - 0171-5216
IS - 5
ER -