Long-term treatment-free remission of chronic myeloid leukemia with falling levels of residual leukemic cells.

2018

Ross, David M

Pagani, Ilaria S

Shanmuganathan, Naranie

Kok, Chung H

Seymour, John F

Mills, Anthony K

Filshie, Robin J

Arthur, Christopher K

Dang, Phuong

Saunders, Verity A

Braley, Jodi

Yong, Agnes S

Yeung, David T

White, Deborah L

Grigg, Andrew P

Schwarer, Anthony P

Branford, Susan

Hughes, Timothy P

Journal Article

0000-0001-7171-2935

10.1038/s41375-018-0264-0

Following the achievement of deep molecular response on tyrosine kinase inhibitors (TKIs), approximately half of patients with chronic myeloid leukemia (CML) can discontinue TKI and remain in treatment-free remission (TFR). The ALLG CML8 study enrolled 40 imatinib-treated patients with undetectable BCR-ABL1 mRNA (approximately MR4.5). Molecular relapse was defined as detectable BCR-ABL1 on two consecutive tests or any single value >0.1%. With a median follow-up of 8.6 years (range 5.7-11.2 years), 18 patients remain in continuous TFR (45.0%; 95% confidence interval 31.9-63.4%). The latest relapse detected was 27 months after stopping imatinib. No patient progressed to advanced phase. Twenty-two patients met criteria for imatinib re-treatment and all regained undetectable molecular response. Nine patients in long-term TFR were monitored by highly sensitive individualized BCR-ABL1 DNA PCR in a sufficient number of samples to enable more precise quantification of residual leukemia. BCR-ABL1 DNA decreased from a median of MR5.0 in the first year of TFR to MR6.1 in the sixth year of TFR. Our results support the long-term safety and remarkable stability of response after imatinib discontinuation in appropriately selected CML patients. Serial high sensitivity testing provides a new and unexpected finding of gradually reducing CML cells in patients in long-term TFR.

link

Leukemia 2018; 32(12): 2572-2579

Leukemia