scholarly journals Characteristics and Outcomes of Unselected Adolescents and Young Adults Patients with Chronic Myeloid Leukemia in the Tyrosine Kinase Inhibitor Era

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1803-1803
Author(s):  
Stéphanie Bernardin ◽  
Franck E. Nicolini ◽  
Delphine Rea ◽  
Mael Haiblig ◽  
Martine Gardembas ◽  
...  
Keyword(s):  
Overall Survival ◽  
Young Adults ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Adolescents And Young Adults ◽  
First Line ◽  
Free Survival

Abstract Chronic myeloid leukemia (CML) is a myeloproliferative disorder with a median age of approximately 60 years (Hoglund M 2013). However, little is known about outcomes in CML in adolescents and young adults. In the literature there are few reports involving only patients enrolled in trials aged from 15 to 30 years (Cortes J 2012, Kalmanti L 2013). We report here the characteristics and outcomes in 78 unselected adolescents and young adults ranging from 18 to 25 years with newly diagnosed CML in chronic (n=73) or in accelerated phase (n=5) in the tyrosine kinase inhibitor (TKI) era from 13 Fi-LMC centers being in possession with local databases. The median follow-up is 56 months (0-144) after diagnosis. Sokal scores were low in 41 (56%) patients, intermediate in 10 (13%), and high in 13 (17%) and unknown in 9 (14%) patients. Five patients had a CCA/Ph+ but were in CP cytologically, at diagnosis. Initial TKI were imatinib alone (n=55) or in combination with IFN (n=3), nilotinib alone (n=5) or in combination (n=1), dasatinib alone (n=10) or in combination (n=1) or ponatinib (n=1). One patient died before treatment initiation from brain hemorrhage, and initial treatment is unknown in one patient. Only 38/76 (50%) of patients remained under TKI first-line at latest follow-up. The reasons of first-line discontinuation were blast crisis (n=3); according to ELN criteria, cytogenetic failures (n=10), molecular failures (n=5), molecular warnings (n=8), mutation (n=1); intolerance (n=6), FDA notification in EPIC study (n=1). The second-line therapies were imatinib (n=2), IFN in combination with aracytine (n=1), nilotinib (n=13), dasatinib (n=13), high-dose chemotherapy alone (n=1) or followed by allogeneic bone marrow transplantation (n=4). 13 patients discontinued their second line TKI for blastic transformations (n=2), cytogenetic failures (n=4), molecular failures (n=2), molecular warning (n=1), mutation (n=1) and intolerance (n=3). The third-line therapies were imatinib (n=1), nilotinib (n=2), dasatinib (n=5), ponatinib (n=1), chemotherapy alone (n=1), allo-transplantation (n=1). Only 25/78 (32%) of patients were included in a trial. Only one patient experimented a 4th line of TKI (ponatinib). We compared characteristics and outcome of the 2 groups of patients, enrolled in first line versus unenrolled (Table 1). There were significantly more men included than women. Accelerated phases and CCA/Ph+ were observed only in the unenrolled group. The overall survival is shown in Figure 1A. Blastic transformation, failure of TKI defined as ELN 2013 recommendations and death were used to calculate the EFS curve (Figure 1B). Finally, we designed a curve representing the probability to remain under first-line TKI: 2nd line TKI-Free Survival (Figure 1C). A complete analysis comparing characteristics and outcome between the 2 groups of patients, will be available for ASH presentation. Table 1: Characteristics of patients Total patients n=78 Enrolled patients n=24 Unenrolled patients n=54 P value Ratio H/F (n) 50/28 18/5 22/32 0.0025 Median age (years) 22 23 22 NS CCA/Ph+ (n) 5 0 5 - Phase (C/A) (n) 73/5 24/0 49/5 NS Sokal (L/I/H/U) (n) 41/10/13/9 16/2/5/1 25/8/8/8 NS Median FU (months) (Range) 56 (0-144) 41 (2-114) 63 (0-144) - Interval from D to 1st line TKI (days) 27 29 24 - 1st line TKI (I/N/D/P/NA)(n) 58/6/11/1/2 9/4/10/1/0 49/2/1/0/2 NS Median 1st line TKI duration (months) 27 26 28 - Discontinuations (n) 38 8 30 0.069 Discontinuation reasons (n) Blastic phase Cytogenetic failure Molecular failure Molecular warning Intolerance Pregnancy Sustained CMR FDA notification Mutation 3 10 5 8 6 2 2 1 1 0 3 3 0 0 0 1 1 0 3 7 2 8 6 2 1 0 1 TKI line Number (1/2/3/4)(n) 38/19/10/1 17/5/2/0 24/12/8/1 - Abbreviations: U unknown; FU follow up; D diagnosis; I imatinib; N Nilotinib; D dasatinib; P Ponatinib; TKI Tyrosine Kinase Inhibitor Figure 1: (A) overall survival from diagnosis of enrolled and unenrolled patients. (B) EFS of enrolled and unenrolled patients. Patients in AP were excluded. (C) 2nd line TKI-Free Survival of enrolled and unenrolled patients corresponding to the probability to remain under first-line TKI. Figure 1:. (A) overall survival from diagnosis of enrolled and unenrolled patients. (B) EFS of enrolled and unenrolled patients. Patients in AP were excluded. (C) 2nd line TKI-Free Survival of enrolled and unenrolled patients corresponding to the probability to remain under first-line TKI. Disclosures Nicolini: Novartis: Consultancy. Gardembas:BMS: Honoraria. Etienne:Novartis, BMS, Pfizer, Ariad: Honoraria. Guerci-Bresler:Novartis, BMS, Pfizer: Honoraria. Roy:Novartis: Honoraria; BMS: Honoraria. Legros:Novartis, BMS: Honoraria.

scholarly journals Current event-free survival after sequential tyrosine kinase inhibitor therapy for chronic myeloid leukemia

Cancer ◽  
2010 ◽  
Vol 117 (2) ◽  
pp. 327-335 ◽  
Author(s):  
Aref Al-Kali ◽  
Hagop Kantarjian ◽  
Jianqin Shan ◽  
Roland Bassett ◽  
Alfonso Quintás-Cardama ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Inhibitor Therapy ◽  
Event Free Survival ◽  
Current Event ◽  
Free Survival ◽  
Tyrosine Kinase Inhibitor Therapy

scholarly journals Early response with dasatinib or imatinib in chronic myeloid leukemia: 3-year follow-up from a randomized phase 3 trial (DASISION)

Blood ◽  
2014 ◽  
Vol 123 (4) ◽  
pp. 494-500 ◽  
Author(s):  
Elias Jabbour ◽  
Hagop M. Kantarjian ◽  
Giuseppe Saglio ◽  
Juan Luis Steegmann ◽  
Neil P. Shah ◽  
...  
Keyword(s):  
Overall Survival ◽  
Myeloid Leukemia ◽  
Progression Free Survival ◽  
Early Response ◽  
First Line ◽  
Phase 3 ◽  
Free Survival ◽  
Key Points ◽  
Treatment Naïve

Key Points In a 3-year follow-up of the DASatinib versus Imatinib Study In treatment-Naive CML patients trial, first-line dasatinib resulted in faster and deeper responses compared with imatinib. Deeper responses at 3, 6, and 12 months were associated with better 3-year progression-free survival and overall survival.

Tyrosine Kinase Inhibitor Discontinuation in Chronic Myeloid Leukemia: Single US Center Experience

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4045-4045
Author(s):  
H Jean Khoury ◽  
Leonard T Heffner ◽  
Martha Arellano ◽  
Anand P Jillella ◽  
Vamsi K Kota ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Median Duration ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Kinase Inhibitor ◽  
Cardiac Transplant ◽  
Tki Discontinuation

Imatinib (IM) can be safely discontinued in patients with chronic myeloid leukemia (CML) with sustained complete molecular remission. Previous publications from France and Australia have shown that overall 40% maintain MMR or MR5 for up to 5 years after IM is stopped. We report single US center experience with tyrosine kinase inhibitor (TKI) discontinuation. Between 06/2010 and 7/2015, 22 patients with CML in chronic (CP, n=19), accelerated (AP, n=2) and lymphoid blast phase (LBP, n=1) discontinued IM (n=17), dasatinib (DAS, n=3) or bosutinib (BOS, n=2), and were monitored by qPCR for BCR-ABL1 monthly for the first 3 months, quarterly for the following 2 years and then bi-annually. TKI was restarted in case of confirmed loss of MMR on a repeat qPCR. Reason for TKI discontinuation was predominantly driven by patients' request and TKI intolerance. Median age was 66 (range, 21-84). The 3 who discontinued DAS had IM-resistant (loss of CCyR; n=1), IM-intolerant CP (n=1), or received DAS as first-line agent (n=1). BOS was discontinued for IM-intolerant CP (n=1), or while in CR2 in a patient with LBP that transformed from IM resistant CP and relapsed following chemotherapy (HCVAD). Median duration of TKI therapy pre-discontinuation for the entire cohort was 89 months (range, 26-106). Three patients are not evaluable due to short follow-up (TKI stopped between 5/2015 and 7/2015). With a median follow-up of 40 months (range, 8-60), 7 (41%, 6 CP and 1 AP), all previously on IM lost MMR a median of 3 months (range, 3-24) after TKI was stopped and restarted IM. Loss of CHR occurred 13 months after loss of MMR in 1 patient who elected not to restart IM at the time MMR was lost, due to complications from cardiac transplant rejection. All 7 achieved MMR following restart of IM. Median duration of TKI therapy pre-discontinuation for these 7 patients was 60 months (range, 48-98). 12 patients (59%, 10 CP, 1 AP, 1 LBP) remain off TKI and have not lost MMR, 8 with continuously undetectable BCR-ABL1; and 4 had 1-2 transient detectable BCR-ABL1 at MR4 levels. Median duration of TKI therapy pre-discontinuation for these 12 patients was 87 months (range, 26-106). Loss of MMR-free survival is depicted in the Figure. We conclude that, similar to previous reports, TKI can be safely discontinued in patients with CML without reappearance of BCR-ABL1 in 50-60%. Figure 1. Figure 1. Disclosures Jillella: Seattle Genetics, Inc.: Research Funding. Kota:Leukemia Lymphoma Society: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees.

First-line tyrosine kinase inhibitor with or without aggressive upfront local radiation therapy in patients with EGFRm oligometastatic non-small cell lung cancer: Interim results of a randomized phase III, open-label clinical trial (SINDAS) (NCT02893332).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9508-9508 ◽  
Author(s):  
Xiaoshan Wang ◽  
Ming Zeng
Keyword(s):  
Overall Survival ◽  
Tyrosine Kinase ◽  
Small Cell Lung Cancer ◽  
Tyrosine Kinase Inhibitor ◽  
Stereotactic Radiotherapy ◽  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival

9508 Background: The effectiveness of aggressive local therapy for oligometastatic non-small-cell lung cancer (NSCLC) is unknown. This multi-institutional, randomized, open label, phase III clinical trial was performed to assess upfront stereotactic radiotherapy to all sites at diagnoses in previously untreated EGFRm oligometastatic non-small-cell lung cancer on progression-free survival and overall survival. Methods: The study was conducted at five centers located in different provinces of China.Eligible participants had pathologically confirmed adenocarcinoma, gene sequencing confirmed EGFRm, stage IV, five or fewer metastatic disease lesions, an ECOG performance status score of ≤ 2, systemic therapy naive, and no brain disease before randomization.Participants were randomized to receive either first-line tyrosine kinase inhibitor (TKI) treatment alone or up front stereotactic radiotherapy to all sites of disease along with TKI treatment.The primary endpoint was progression-free survival and the secondary endpoint was overall survival. Results: From January 2016 to January 2019, 133 participants were enrolled, including 65 (48.8%) in the TKI arm who received standard of care TKI alone and 68 (51.1%) in the stereotactic radiotherapy sites at diagnosis arm who received stereotactic radiotherapy and TKI.At a median follow-up of 19.6 months (IQR 9.4 - 41.0), the median progression-free survival for tyrosine kinase inhibitor alone was 12.5 months, and for tyrosine kinase inhibitor and stereotactic radiotherapy was 20.20months, respectively (HR 0.6188 [95% CI 0.3949-0.9697], log rank P< .001). The median overall survival in the TKI alone arm was 17.40 months, and for TKI and stereotactic radiotherapy arm was 25.50 months, respectively (HR 0.6824 [95% CI 0. 4654-1.001], log rank P< .001). Adverse events were similar between groups, with no grade 5 or deaths due to treatment. Grade 3/4 adverse events with or without radiotherapy included pneumonitis (7.3% vs. 2.9%; P> .05) and esophagitis (4.4%vs. 3.0% P> .05). Conclusions: Upfront stereotactic radiotherapy to sites at diagnosis along with first line TKI improved both progression-free survival and overall survival significantly compared with TKI alone. This finding suggests aggressive local therapy to sites at diagnosis should be explored further in large cohort phase III trials as a standard treatment option in this clinical scenario. Clinical trial information: NCT02893332 .

scholarly journals Results of following up patients with chronic myeloid leukemia and a deep molecular response without tyrosine kinase inhibitor therapy

2017 ◽  
Vol 89 (12) ◽  
pp. 86-96 ◽  
Author(s):  
A G Turkina ◽  
E Yu Chelysheva ◽  
V A Shuvaev ◽  
G A Gusarova ◽  
A V Bykova ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Molecular Response ◽  
Therapy Discontinuation ◽  
Deep Molecular Response ◽  
Tki Discontinuation

Aim. To assess the results of following up patients with chronic myeloid leukemia (CML) and a deep molecular response (MR) without tyrosine kinase inhibitor (TKI) therapy. Subjects and methods. The reasons for TKI discontinuation in 70 patients with CML and a deep MR of more than 1 year’s duration were adverse events, pregnancy, and patients’ decision. Information was collected retrospectively and prospectively in 2008-2016. Results. The median follow-up after TKI therapy discontinuation was 23 months (2 to 100 months). At 6, 12 and 24 months after TKI therapy discontinuation, the cumulative incidence of major MR (MMR) loss was 28, 41 and 48%, respectively; the survival rates without TKI therapy were 69, 50, and 39%, respectively. MMR loss was noted in 28 (88%) patients at 12 months; it was not seen without TKI therapy at 2-year follow-up. Deaths due to CML progression were absent. The Sokal risk group was a reliable factor influencing MMR loss (p ≤ 0.05). The cumulative recovery rate for deep MR after resumption of TKI use was 73 and 100% at 12 and 24 months, respectively, with a median follow-up of 24 months (1 to 116 months). Deep MR recovered at a later time when the therapy was resumed more than 30 days after MMR loss. Conclusion. Safe follow-up is possible in about 50% of the patients with CML and stable deep MRs without TKI therapy. The introduction of this approach into clinical practice requires regular molecular genetic monitoring and organizational activities. Biological factors in maintaining remission after TKI discontinuation need to be separately studied.

scholarly journals Combination of Dasatinib and Pediatric-Inspired Regimens in Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Single-Center Prospective Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2583-2583
Author(s):  
Zhang Guang ji ◽  
Jianxiang Wang ◽  
Ying Wang ◽  
Hui Wei ◽  
Yingchang Mi
Keyword(s):  
Overall Survival ◽  
Acute Lymphoblastic Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Kinase Inhibitor ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Molecular Response ◽  
Newly Diagnosed ◽  
Free Survival

Background: Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is a rare subtype of acute lymphoblastic leukemia with a poor long-term prognosis. Recent studies suggested that the addition of tyrosine kinase inhibitor (TKI) to the traditional chemotherapy treatment has significantly improved Ph+ ALL patients response rates, disease-free survival, and overall survival (OS). Dasatinib, a second-generation tyrosine kinase inhibitor, can pass the blood-brain barrier and possesses a stronger inhibitory effect on both SRC kinase and BCR-ABL. In theory, it might be beneficial in Ph+ ALL treatment. This prospective, single-arm study assesses the efficacy of a combination of dasatinib and pediatric-inspired regimens in Ph+ ALL patients. Methods: 30 patients from the Institute of Hematology and Blood Diseases Hospital were enrolled in this study from January 2016 to April 2018. Eligible subjects were newly diagnosed Ph+ ALL adult patients. Chemotherapy regimens were initiated after the pediatric-inspired regimens, and standard induction chemotherapy was given for four weeks. Seven courses of consolidation or hematopoietic cell transplantation (HCT) were given to those who have achieved hematological complete remission (HCR). The primary objectives of this study were the HCR and molecular complete response (MCR), the major molecular response (MMR), the overall survival (OS), and the hematologic relapse-free survival (HRFS). The median follow-up time was 28 months. The trial registration number is NCT02523976. Results : 30 subjects were enrolled in this study with a median age of 37.5 years (range 19-50 years). All patients achieved HCR after four weeks of induction therapy with a cumulative MCR rate of 87.5%(21/24). The median HRFS and median OS were 19.5 (range 2-40 months) and 21 (range 7-41 months), respectively. The molecular response, assessed through monitoring of BCR-ABL transcript expression, revealed that 61.3% of the patients reached MMR and MCR after three months of treatment. Additionally, the results indicated that patients who achieved MCR in the first three months had a better HRFS (p=0.038). Fifteen of the patients (50%) proceeded to stem cell transplantation (SCT) within the first HCR period (SCT in HCR1). Only 13.3% (2/15) of the SCT cohort relapsed, and 20% (3/15) died. It is worth mentioning that the SCT in HCR1 cohort had better HRFS (P=0.03). Most adverse events were reversible, and none of the subjects had pulmonary hypertension. Conclusion: These findings indicate that an early MCR (3 months) has a positive impact on patients survival and that Dasatinib, combined with pediatric-inspired regimens, is effective and leads to a high MCR in patients with newly diagnosed Ph+ALL. Disclosures No relevant conflicts of interest to declare.

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