Contributions
Abstract: PB1815
Type: Publication Only
Background
Imatinib (IM) and its generic form are widely used as one of the standards of care for chronic phase (CP) chronic myeloid leukemia (CML). Although 7-year data by the IRIS demonstrated the long-term prognostic value of molecular response at specific time points, achieving major molecular response (MMR) at 18 months showed minimal event-free survival (EFS) benefit, compared with not achieving MMR but having complete cytogenetic response (CCyR). In addition, the best treatment for these patients remains less clear.
Aims
In this study, we investigated the efficacy of nilotinib (NIL) versus high-dose IM versus sustaining standard-dose IM for the patients in CCyR with suboptimal molecular response to first-line IM therapy.
Methods
Early CP CML patients who have achieved CCyR but not MMR after 18 to 24 months on first-line IM therapy at a daily dose of 400 mg were divided into the three treatment groups; nilotinib (NIL) 400mg BID (800 mg/day; group 1) vs IM 400 mg BID (800 mg/day; group 2) vs IM 400mg QD (400mg/day; group 3). Group 1 and 2 patients were selected in the RE-NICE multicenter study, in which crossover to the alternate treatment arm was allowed for patients failing to achieve a MMR at 12 months and for intolerant patients, and for patients who lost MMR at any time of treatment. Group 3 patients who have achieved CCyR but not MMR after at least 18 months of first-line IM therapy were selected from the Asia CML Registry (ACR) database system with the same inclusion criteria of RE-NICE. The efficacy endpoints are MMR rate by 12 months and MMR rate and undetectable molecular residual disease (UMRD) rates by 36 months.
Results
With a data cut-off date of 07 Dec 2016, a total of 108 patients were evaluated; 28 patients in NIL group (group 1), 28 patients in high-dose IM group (group 2), and 52 patients in standard-dose IM group (group 3). Median follow-up duration from enrollment was 36 months (range, 1-36), 45 months (range, 21-63), and 90 months (range, 14-159) for each group, respectively. All patients in group 1 remained NIL treatment, 18 patients in group 2 crossed over to NIL 400mg BID due to intolerance (n=4) and lack of response (no MMR after 12 months; n=14), in group 3, 22 patients switched to other treatment due to intolerance (n=7), lack of response (no MMR; n=12), failure (n=1), or treatment-free remission trial (n=2) and 2 patients lost to follow-up. When data on patients who crossed over to the other treatment was included, cumulative incidence (CI) of MMR by 36 months was significantly higher in group 1 than group 3 (83.1% vs 57.1%, P=0.021), but there was no different in group 1 vs 2 (P = 0.195) and group 2 vs 3 (P = 0.297). CI of MR4.5 by 36 months showed a trend of higher in group 1 than the other two group (11.7% vs 0% vs 2.6%, group 1 vs 2, P=0.066, group 1 vs 3, P=0.099, group 2 vs 3, P=0.405).
Conclusion
NIL 400mg twice daily treatment showed better efficacy than standard-dose IM for the treatment of patients who have suboptimal molecular response to first-line IM. Additionally, a switch to NIL in suboptimal molecular responder to IM had a trend for achieving a MR4.5 more frequently, suggesting the potential benefit of a treatment-free remission.
Session topic: 8. Chronic myeloid leukemia - Clinical
Keyword(s): Molecular response, Chronic myeloid leukemia
Abstract: PB1815
Type: Publication Only
Background
Imatinib (IM) and its generic form are widely used as one of the standards of care for chronic phase (CP) chronic myeloid leukemia (CML). Although 7-year data by the IRIS demonstrated the long-term prognostic value of molecular response at specific time points, achieving major molecular response (MMR) at 18 months showed minimal event-free survival (EFS) benefit, compared with not achieving MMR but having complete cytogenetic response (CCyR). In addition, the best treatment for these patients remains less clear.
Aims
In this study, we investigated the efficacy of nilotinib (NIL) versus high-dose IM versus sustaining standard-dose IM for the patients in CCyR with suboptimal molecular response to first-line IM therapy.
Methods
Early CP CML patients who have achieved CCyR but not MMR after 18 to 24 months on first-line IM therapy at a daily dose of 400 mg were divided into the three treatment groups; nilotinib (NIL) 400mg BID (800 mg/day; group 1) vs IM 400 mg BID (800 mg/day; group 2) vs IM 400mg QD (400mg/day; group 3). Group 1 and 2 patients were selected in the RE-NICE multicenter study, in which crossover to the alternate treatment arm was allowed for patients failing to achieve a MMR at 12 months and for intolerant patients, and for patients who lost MMR at any time of treatment. Group 3 patients who have achieved CCyR but not MMR after at least 18 months of first-line IM therapy were selected from the Asia CML Registry (ACR) database system with the same inclusion criteria of RE-NICE. The efficacy endpoints are MMR rate by 12 months and MMR rate and undetectable molecular residual disease (UMRD) rates by 36 months.
Results
With a data cut-off date of 07 Dec 2016, a total of 108 patients were evaluated; 28 patients in NIL group (group 1), 28 patients in high-dose IM group (group 2), and 52 patients in standard-dose IM group (group 3). Median follow-up duration from enrollment was 36 months (range, 1-36), 45 months (range, 21-63), and 90 months (range, 14-159) for each group, respectively. All patients in group 1 remained NIL treatment, 18 patients in group 2 crossed over to NIL 400mg BID due to intolerance (n=4) and lack of response (no MMR after 12 months; n=14), in group 3, 22 patients switched to other treatment due to intolerance (n=7), lack of response (no MMR; n=12), failure (n=1), or treatment-free remission trial (n=2) and 2 patients lost to follow-up. When data on patients who crossed over to the other treatment was included, cumulative incidence (CI) of MMR by 36 months was significantly higher in group 1 than group 3 (83.1% vs 57.1%, P=0.021), but there was no different in group 1 vs 2 (P = 0.195) and group 2 vs 3 (P = 0.297). CI of MR4.5 by 36 months showed a trend of higher in group 1 than the other two group (11.7% vs 0% vs 2.6%, group 1 vs 2, P=0.066, group 1 vs 3, P=0.099, group 2 vs 3, P=0.405).
Conclusion
NIL 400mg twice daily treatment showed better efficacy than standard-dose IM for the treatment of patients who have suboptimal molecular response to first-line IM. Additionally, a switch to NIL in suboptimal molecular responder to IM had a trend for achieving a MR4.5 more frequently, suggesting the potential benefit of a treatment-free remission.
Session topic: 8. Chronic myeloid leukemia - Clinical
Keyword(s): Molecular response, Chronic myeloid leukemia