Safety of a second-generation tyrosine kinase inhibitor and novel targeted therapy for the treatment of a patient with chronic myeloid leukemia and multiple myeloma

2015 ◽  
Vol 26 (8) ◽  
pp. 907-909 ◽  
Author(s):  
Jed A. Katzel ◽  
Annette Lee-Ma ◽  
David H. Vesole
Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2569-2569
Author(s):  
Nancy Cribb ◽  
Tazmin Merali ◽  
Bonnie MK Donato

Abstract Abstract 2569 Background: New treatment options in chronic myeloid leukemia (CML) have become available in the past years. However, there is a scarcity of published data documenting how patients are treated as well as the impact of the treatment of CP-CML in Canada. Objective: To describe current treatment patterns and clinical outcomes of CP-CML patients receiving treatment in Canada. Methods: Treatment data on CP-CML patients was extracted from a cancer patient treatment summary database, ONCO-CAPPS. The database is comprised of treatment summaries of over 12,000 Canadian cancer patients from across the country. For the study, CP-CML patients aged 18 years or older, who received 400mg of imatinib as 1st-line treatment, and who completed at least 4 continuous weeks of this treatment between October 1, 2008 and December 31, 2009, were eligible for study inclusion. Results: A total of 301 patients met the selection criteria. At the time of review, 62% of patients had a confirmed diagnosis of CP-CML for 2 years or more. Of the CP-CML patients in the study who were prescribed 400mg of imatinib as their initial CP-CML treatment, 51% (155/301) received a 2nd line treatment option, either a dose modification or a change of therapy. Of those requiring 2nd line treatment, 32% (50/155) of patients received an increase in their imatinib dose, resulting in an average daily dose of 664 mg, and representing a 66% increase in the dose of imatinib. Average response times for patients who received an increase in imatinib dose for Complete Hematological Response (CHR) was 183 days, for Complete Cytogenetic Response (CCyR) was 671 days, and for Major Molecular Response (MMR) was 971 days. These response times exceed both Canadian Consensus Guidelines as well as the 2009 ELN (European Leukemia Network) recommendations. Furthermore, 45% (69/155) of patients receiving a 2nd line CML treatment experienced intolerance to imatinib 400 mg resulting in dose decrease or treatment interruption. Switching to second generation tyrosine kinase inhibitor agents (dasatinib or nilotinib) due to inadequate response, loss of response or intolerance to imatinib occurred in 20% of the population. Conclusions: Analysis of Canadian patients over time revealed that 51% of CP-CML patients initiated on 400mg imatinib received 2nd line treatment. The most frequent modification was due to intolerance. Of note, 32% received a dose escalation, which was more common than switching to a second generation tyrosine kinase inhibitor. Furthermore, response times observed amongst patients in this study whose imatinib dose was escalated exceeded timelines for treatment response determination as noted in both internationally and locally recognized treatment guidelines. Published research demonstrates that delays in achieving response are associated with increased risk of progression among patients with CML. Disclosures: Cribb: Drug Intelligence Inc.: Research Funding. Merali:Bristol-Myers Squibb Canada: Research Funding. Donato:Drug Intelligence Inc.: Research Funding.


2016 ◽  
Vol 38 (3) ◽  
pp. 195-197 ◽  
Author(s):  
S V Andreieva ◽  
K V Korets ◽  
O A Kyselova ◽  
O E Ruzhinska ◽  
I M Serbin

Aim: Genetic inborn along with acquired diseases arise due to the lesions in genome of multipotent hematopoietic stem cells. The aim was to study an influence of constitutional anomaly, Klinefelter syndrome, and additional structural rearrangements on the BCR-ABL tyrosine kinase inhibitor targeted therapy efficacy. Material and Methods: We describe a 32-year-old male patient with chronic myeloid leukemia (CML) who was detected to have sex chromosomal abnormality during evaluation for Philadelphia chromosome. Results: At diagnosis of CML, two clones were detected by standard cytogenetic investigation of bone marrow cells: 1) clone with translocation t(9;22)(q34;q11), with two sex X chromosomes and absence sex chromosome Y; 2) clone with t(9;22) and unbalanced t(Y;20)(q11;q13). Analysis of blast transformed lymphocytes from peripheral blood showed karyotype 47,XXY. Monitoring of targeted therapy with second generation inhibitor of BCR-ABL tyrosine kinase indicated a cytogenetic remission and absence of BCR-ABL1 fusion signals after 11 months. Conclusions: Absence of translocation t(9;22)(q34;q11) in blast transformed T-lymphocytes at diagnosis of CML evidences that this translocation may appear not only at the level of multipotent haemopoietic cell progenitors but also may have oligo lineage myeloid origin. Presence of additional structural chromosomal abnormality in the clone with t(9;22)(q34;q11) does not affect the efficacy of therapy with the use of second generation BCR-ABL tyrosine kinase inhibitor.


2015 ◽  
Vol 6 (2S) ◽  
pp. 7-10
Author(s):  
Raffaele Porrini ◽  
Enrico Montefusco

In this article we present the case of a 43-year-old man with chronic myeloid leukemia (CML) successfully treated with nilotinib. At presentation we started him on imatinib at standard dose of 400 mg/day but after 36 months of treatment the patient didn’t achieve a molecular response. We switched him on second-generation tyrosine kinase inhibitor (TKI), nilotinib, at the dose of 800 mg/day. After twelve months on nilotinib the patient obtained a complete molecular response. During treatment with nilotinib we did not observe any drug-related toxicity.


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