Outcomes of Chronic Phase Chronic Myeloid Leukemia after Treatment with Multiple Tyrosine Kinase Inhibitors.

Jee Hyun Kong,Brittany Hill,Elliott F Winton,Leonard T Heffner,Jean Hanna Khoury,Meena Joseph,Angela Hatcher,Manila Gaddh,Martha Arellano,Audrey Kim,Jessica Neely,Fuad El-Rassi,Vamsi K Kota

doi:10.3390/jcm9051542

Abstract

We sought to evaluate the outcomes of chronic phase (CP) chronic myeloid leukemia (CML) in an era where five tyrosine kinase inhibitors (TKIs) are commercially available for the treatment of CML. Records of patients diagnosed with CP CML, treated with TKIs and referred to our center were reviewed. Between January 2005 and April 2016, 206 patients were followed for a median of 48.8 (1.4–190.1) months. A total of 76 (37%) patients received one TKI, 73 (35%) received two TKIs and 57 (28%) were exposed to >3 TKIs (3 TKIs, n = 33; 4 TKIs, n = 17; 5 TKIs, n = 7). Nineteen (9.2%) patients progressed to advanced phases of CML (accelerated phase, n = 6; myeloid blastic phase, n = 4; lymphoid blastic phase, n = 9). One third (n = 69) achieved complete molecular response (CMR) at first-line treatment. An additional 55 patients achieved CMR after second-line treatment. Twenty-five patients (12.1%) attempted TKI discontinuation and 14 (6.8%) stopped TKIs for a median of 6.3 months (range 1–53.4). The 10-year progression-free survival and overall survival (OS) rates were 81% and 87%, respectively. OS after 10-years, based on TKI exposure, was 100% (1 TKI), 82% (2 TKIs), 87% (3 TKIs), 75% (4 TKIs) and 55% (5 TKIs). The best OS was observed in patients tolerating and responding to first line TKI, but multiple TKIs led patients to gain treatment-free remission.

Highlights

Chronic myeloid leukemia (CML) is a clonal myeloproliferative stem cell disorder characterized by the presence of a signature hybrid oncogene, the BCR-ABL1 [1]
We evaluated the real-world practice of treating chronic phase (CP) CML in the era of multiple tyrosine kinase inhibitor (TKI) and analyzed the long-term outcomes and any associated factors
The best overall survival (OS) was observed in patients tolerating and responding to first-line TKI treatment, and the worst was observed in those treated with 5 TKIs (Figure 1b)

Summary

Introduction

Chronic myeloid leukemia (CML) is a clonal myeloproliferative stem cell disorder characterized by the presence of a signature hybrid oncogene, the BCR-ABL1 [1]. The ABL1 gene encodes non-receptor tyrosine kinases that become deregulated and constitutively active by the juxtaposition of BCR. The understanding of the pathophysiology of CML led to the development of drugs that target the tyrosine kinase activity of BCR-ABL. There are five tyrosine kinase inhibitors (TKIs) approved for the treatment of CML: Imatinib (IM, Gleevec®, Novartis Oncology, East Hanover, NJ, USA), dasatinib (DAS, Sprycel®, Bristol-Meyers Squibb Company, Princeton, NJ, USA), nilotinib (NIL, Tasigna®, Novartis Oncology, East Hanover, NJ, USA), bosutinib (BOS, Bosulif®, Pfizer, New York, NY, USA) for both first and second-line therapy, and ponatinib (PON, Iclusig®, Ariad Pharmaceuticals, Cambridge, MA, USA) for patients with the T315I mutation or for whom no other TKI is indicated. The outcome of patients requiring multiple TKI treatments in chronic phase (CP) CML has not been well established. We sought to evaluate the outcomes of CP CML in an era where several TKIs are available

Materials and Methods

Clinical Outcomes

Outcomes According to First-Line TKI

TKI Discontinuation

Findings

Discussion