THE POTENTIAL IMPACT OF SWITCH TO SECOND GENERATION TYROSINE KINASE INHIBITORS IN CHRONIC MYELOID LEUKEMIA PATIENTS IN CHRONIC PHASE WHO HAD NO OPTIMAL RESPONSE TO 3 MONTHS OF INITIAL IMATINIB THERAPY
Author(s): ,
Olga Vinogradova
Affiliations:
Moscow City Hematology Center,Botkin Hospital,Moscow,Russian Federation;Rogachev National Research Center for Pediatric Hematology, Oncology & Immunology,Moscow,Russian Federation;Pirogov Russian National Research Medical University,Moscow,Russian Federation
,
Maria Pankrashkina
Affiliations:
Moscow City Hematology Center,Botkin Hospital,Moscow,Russian Federation;Rogachev National Research Center for Pediatric Hematology, Oncology & Immunology,Moscow,Russian Federation
,
Dzhariyat Shikhbabaeva
Affiliations:
Moscow City Hematology Center,Botkin Hospital,Moscow,Russian Federation
,
Mikhail Chernikov
Affiliations:
Research Institute for Health Care Organization & Medical Management,Moscow,Russian Federation
,
Svetlana Tsareva
Affiliations:
Moscow City Hematology Center,Botkin Hospital,Moscow,Russian Federation;Research Institute for Health Care Organization & Medical Management,Moscow,Russian Federation
,
Yuri Kobzev
Affiliations:
Moscow City Hematology Center,Botkin Hospital,Moscow,Russian Federation
,
Natalia Novitskaya
Affiliations:
Moscow City Hematology Center,Botkin Hospital,Moscow,Russian Federation
,
Evgeniya Arshanskaya
Affiliations:
Moscow City Hematology Center,Botkin Hospital,Moscow,Russian Federation
Vadim Ptushkin
Affiliations:
Moscow City Hematology Center,Botkin Hospital,Moscow,Russian Federation;Rogachev National Research Center for Pediatric Hematology, Oncology & Immunology,Moscow,Russian Federation;Pirogov Russian National Research Medical University,Moscow,Russian Federation
EHA Library. Pankrashkina M. Jun 15, 2019; 266800; PS1183
Maria Pankrashkina
Maria Pankrashkina
Contributions
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Abstract

Abstract: PS1183

Type: Poster Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 17:30 - 19:00

Location: Poster area

Background
Studies have demonstrated that administration of second generation tyrosine kinase inhibitors (2nd gen TKIs) in chronic myeloid leukemia (CML) patients (pts) in chronic phase (CP-CML) had allowed to obtain deeper remissions than with the use of imatinib (IM). Yet with less side effects and being more accessible for pts, IM became a TKI of choice for 1st line CML therapy. It was also shown that pts with optimal response to 3 months (mo) of TKI therapy (BCR/ABL1 ≤ 10% on the International Scale (IS) and/or ≤ 35% of Ph-positive metaphases) have an improved probability of deep molecular responses and superior progression-free and overall survival (PFS and OS). Still, there are a few data supporting change from IM therapy to 2nd gen TKI therapy when no optimal response to 3 mo of IM treatment had been achieved. 

Aims

To evaluate the potential benefits of switching from IM to 2nd gen TKIs in CP-CML pts without optimal response to 3 mo of IM therapy.

Methods
We conducted open prospective observational study during which CP-CML pts at Moscow City Hematology Center with full hematological response but with no optimal response (BCR-ABL1 > 10% IS and/or Ph-positive metaphases of > 35%) after 3 mo of IM 400 mg once daily were switched to 2nd gen TKIs. IM therapy must have been started within 6 mo of the initial CML-CP diagnosis (dx).  A particular 2nd gen TKI selection was based on a BCR/ABL1 mutational status, patient comorbidity and a drug toxicity profile. A primary endpoint was the rate of major molecular response (MMR) (BCR-ABL1 < 0.1% IS) at 12 mo after initiation of IM treatment. Secondary endpoints included rates of MMR at 24 and at 36 mo of TKI therapy; and rates of MR4, МR4,5, PFS and OS at 12, 24 and 36 mo of TKI therapy. 

Results

Study included 76 CP-CML pts with no optimal response to 3 mo of IM therapy. Group 1 (G1) included 33 pts (43%) who were switched to 2nd gen TKIs (dasatinib: n=19; nilotinib: n=12, bosutinib: n=2), while the rest of pts (group 2 – G2) (n=43, 57%) continued with IM. In G1, 17 (52%) were males и 16 (48%) – females, median age at CML dx was 55 (range 20 – 82) years, median follow-up time at the time of analysis was 39 mo. G2 comprised of 21 (49%) males и 22 (51%) females, median age at CML dx was 57 (range 22 – 81) years, median follow-up time was 56 mo.

At 12, 24 and 36 mo of TKI therapy:

Respective rates of MMR were: 39%, 67% and 76% in G1 pts, and 12%, 19% and 35% in G2 pts (P<0.05).  

Respective rates of MR4 were: 21%, 39% and 48% in G1 pts, and 7%, 12% and 16% in G2 pts (P<0.05).

Respective rates of МR4,5 were: 12%, 21%, and 36 % in G1 pts, and 5%, 7% and 14% in G2 pts (P<0.05).

At the same time points, PFS in G1 pts was 91% (at each time point), and in G2 pts - 95%, 93% and 91%, respectively. At 12 and 24 mo of therapy, OS at both groups was the same (100%). At 36 mo of therapy, 97% of G1 pts and 92% of G2 pts remained alive. 

Conclusion
Switch to 2nd gen TKIs of CP-CML pts who had no optimal response to 3 months of initial imatinib therapy has improved their rates of MMR, MR4 and MR4,5. After 36 mo follow-up, no statistically significant differences were seen in PFS and OS. Longer follow-up and larger number of pts enrolled are required to fully assess the potential benefits of such treatment change.

Session topic: 8. Chronic myeloid leukemia - Clinical

Keyword(s): Chronic myeloid leukemia, Molecular response, Therapy, Tyrosine kinase inhibitor

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