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Results of a retrospective, population-based study of patients with chronic phase chronic myeloid leukemia (CML) conducted in Sweden showed approximately one-quarter of evaluable patients interrupted or discontinued BCR/ABL1 tyrosine kinase inhibitor (TKI) therapy for 1 month or longer due to a deep molecular response (DMR) to treatment. These findings were presented at the Virtual Edition of the 25th European Hematology Association (EHA) Annual Congress.1
According to National Comprehensive Cancer Network (NCCN) guidelines, the recommended first-line treatment for patients diagnosed with chronic phase CML is oral, single-agent BCR/ABL1 TKI therapy, including the first-generation TKI, imatinib, or the second-generation TKIs, bosutinib, dasatinib, or nilotinib.2
Results of clinical trials conducted over the last several years have shown that approximately 40% to 50% of patients with chronic CML characterized by a TKI therapy–related DMR, defined as a molecular response (MR) of 4.0 (4 log reduction) corresponding to a BCR-ABL1 transcript level of 0.01% or lower on the International Scale, were able to successfully interrupt/discontinue TKI therapy.2 In these studies, most patients with subsequent disease relapse were able to regain disease control after reinitiation of TKI therapy.
Based on those findings, the current version of the Swedish CML guidelines includes a recommendation to consider TKI discontinuation in patients who have undergone TKI therapy for at least 5 years and who have achieved an MR of at least 4.0 for at least the last 2 years.However, data are limited regarding the outcomes of patients with chronic phase CML who discontinue TKI therapy outside of a clinical trial setting.
This study included 548 patients diagnosed with CML during 2007 to 2012 included in the Swedish CML registry and a TKI interruption of at least 1 month was documented in 235 (42.8%) patients. The reason for TKI interruption in this subgroup of patients was achievement of a DMR (56% of DMR subgroup and 24% of all patients included in the analysis), experiencing an adverse event (18% of DMR subgroup; 7.8% of all patients), undergoing allogeneic stem cell transplantation (13% of DMR subgroup; 5.7% of all patients), and other (12% of DMR subgroup; 5.3% of all patients).
With a median time of 2.9 years from TKI interruption to last follow-up, 48.9% of patients in the DMR subgroup had reinitiated TKI treatment at a median of 0.4 years from treatment interruption. However, 51.1% of patients in the DMR subgroup (12% of patients in the overall group) remained treatment free at a medium follow-up of 9 years from diagnosis of CML.
Of the 131 patients who had interrupted TKI therapy because of a DMR, 38 (29%) and 92 (70%) were receiving treatment within or outside of a clinical trial, respectively. A comparison of these 2 patient subgroups showed a longer median time from diagnosis to TKI interruption/discontinuation in those treated outside of a clinical trial (6.0 years) compared to those treated within a clinical trial (4.2 years).
Of note, more patients treated outside of a clinical trial received nilotinib compared with patients in clinical trials (29.4% vs 23.7%, respectively) or dasatinib (21.7% vs 15.8%, respectively) as last TKI prior to TKI discontinuation. In addition, the net probability of remaining TKI treatment-free at 24 months following TKI interruption/discontinuation was 61% and slightly less than 30% for those treated off and on a clinical trial, respectively.
In his concluding remarks, Hjalmar Flygt, MD, from the Department of Medical Sciences and Division of Hematology at the University of Uppsala in Sweden, noted that the reasons for a higher treatment-free remission rate in the group treated outside of a clinical trial may be related to the longer duration of therapy before TKI interruption/discontinuation and/or more frequent use of a second-generation TKIs in this group.
Referring back to the finding that only 12% of patients in the overall group were able to remain treatment-free for a long period time, Dr Flygt concluded that “sustained treatment-free remission is currently only a reality for a small proportion of patients.”
- Flygt H, Sandin F, Dreimane A, et al. High level of successful TKI discontinuation outside clinical trials – a population-based study from the Swedish CML registry. Presented at: Virtual Edition of the 25th European Hematology Association (EHA) Annual Congress; June 2020. Abstract S174.
- National Comprehensive Cancer Network (NCCN) Chronic Myeloid Leukemia Guidelines. V3.2020. https://www.nccn.org/professionals/physician_gls/pdf/cml.pdf. Published January 30,2020. Accessed June 7, 2020.
This article originally appeared on Cancer Therapy Advisor