Seven-Year Follow-up of Patients Receiving Imatinib for the Treatment of Chronic Myelogenous Leukemia by the TARGET System

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2287-2287
Author(s):  
Tetsuzo Tauchi ◽  
Masahiro Kizaki ◽  
Shinichiro Okamoto ◽  
Hideo Tanaka ◽  
Mitsune Tanimoto ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Myelogenous Leukemia ◽  
Imatinib Therapy ◽  
Target System ◽  
High Survival ◽  
Molecular Response ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Number Of Patients

Abstract Abstract 2287 The TARGET system is an online database that can be easily accessed by physicians. The TARGET system is operated by the Japanese Society of Hematology. The registration of one's own chronic myeloid leukemia (CML) patients in the TARGET system makes it possible to share experiences among physicians, and, thus, may facilitate appropriate treatment for patients. Patients participating in clinical trials are usually selected according to strict eligibility criteria. Previous publications have questioned the use of other overly restrictive exclusion criteria in clinical oncology trials. In practical situations, however, the clinical features of patients are much more heterogeneous than those defined by the selection criteria in clinical trials. From this point of view, the TARGET system might provide more practical and general features compared with the IRIS study. Patients were registered in the TARGET system from October 2003 to March 2010 in Japan. A total of 1,236 patients from 176 hospitals were registered in Japan. We analyzed data from 639 CML chronic phase patients not receiving prior therapy registered in this system. After 90 months follow-up, high survival rates were demonstrated for imatinib-treated newly diagnosed CML patients, with event-free survival (EFS), progression-free survival (PFS), and overall survival (OS) rates of 79.1, 94.8, and 95.1%, respectively. A landmark analysis of 296 patients who showed a complete cytogenetic response (CCyR) at 12 months after the initiation of imatinib treatment revealed that, at 90 months, 99% of patients (95% CI, 98 to 100) had not progressed to accelerated phase (AP) or blastic crisis (BC). The patients showing a CCyR and a reduction of at least 3 log levels of BCR-ABL transcripts after 18 months of treatment had an estimated survival rate without CML progression of 100% at 84 months.By 84 months, 315 patients had achieved an MMR. A total of 226 of 315 patients (71.7%) achieved undetectable BCR-ABL by 84 months. We therefore analyzed the probability of achieving undetectable BCR-ABL based on the molecular response at 12 and 18 months. The probability of achieving undetectable BCR-ABL by 72 months in patients with an MMR at 12 months was 86.5%, compared with 64.7% for those without an MMR (P<0.0001). Also, the probability of achieving undetectable BCR-ABL based on the molecular response for patients with an MMR at 18 months was 91.9%, compared with 65.3% for those without an MMR (P<0.0001). Therefore, having an MMR at 12 or 18 months of imatinib therapy is highly predictive of subsequent undetectable BCR-ABL. However, the TARGET data indicate a marked increase in the number of patients with undetectable BCR-ABL without an MMR at 12 months compared with IRIS sub-meta-analysis (64.7 vs. 5%, respectively). There were no new safety issues. In summary, based on this 7-year TARGET analysis, imatinib showed a continual clinical benefit as first-line therapy for newly diagnosed CML. The data from TARGET shows that Japanese patients contain a large number of late responders to imatinib therapy. The TARGET system may represent a more practical and general feature compared with the IRIS study. Disclosures: Tauchi: Novartis Pharma KK: Research Funding.

Imatinib Is Effective in Children With Previously Untreated Chronic Myelogenous Leukemia in Early Chronic Phase: Results of the French National Phase IV Trial

2011 ◽  
Vol 29 (20) ◽  
pp. 2827-2832 ◽  
Author(s):  
Frédéric Millot ◽  
André Baruchel ◽  
Joelle Guilhot ◽  
Arnaud Petit ◽  
Thierry Leblanc ◽  
...  
Keyword(s):  
Prospective Trial ◽  
Chronic Phase ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Cytogenetic Response ◽  
Myelogenous Leukemia ◽  
Molecular Response ◽  
Newly Diagnosed ◽  
Free Survival

Purpose Imatinib is the standard of care in adults with chronic myeloid leukemia (CML) in chronic phase (CP). Only a few studies to assess efficacy in children have been performed. We report on the results of the French prospective trial (ClinicalTrials.gov identifier NCT00845221) conducted in children and adolescents with newly diagnosed CML in CP. Patients and Methods A total of 44 patients from age 10 months to 17 years with newly diagnosed CML in CP received daily imatinib 260 mg/m2. Progression-free survival, responses, and tolerance were evaluated. Results With a median follow-up times of 31 months (range, 11 to 64 months), the estimated progression-free survival rate at 36 months was 98% (95% CI, 85% to 100%). A complete hematologic response was achieved in 98% of the patients. The rates of complete cytogenetic response (CCyR) and major molecular response (MMR) were 61% and 31% at 12 months, respectively. During follow-up, CCyR and MMR were achieved in 36 children (77%) and 25 children (57%), respectively. Overall, 30% of the patients discontinued imatinib, mainly because of unsatisfactory response. The most common adverse events were neutropenia and musculoskeletal events. Conclusion Imatinib is effective in children with CML in CP with response rates similar to rates reported in adults. The adverse effects are acceptable, but longer follow-up studies are required to fully assess the long-term impact.

BCR-ABL Levels Continue To Decrease up to 42 Months after Commencement of Standard Dose Imatinib in Patients with Newly Diagnosed Chronic Phase CML Who Achieve a Major Molecular Response.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 274-274 ◽  
Author(s):  
Susan Branford ◽  
Z. Rudzki ◽  
A. Grigg ◽  
J. F. Seymour ◽  
K. Taylor ◽  
...  
Keyword(s):  
Cell Mass ◽  
Chronic Phase ◽  
Imatinib Therapy ◽  
Rapid Progression ◽  
Molecular Response ◽  
Newly Diagnosed ◽  
Major Molecular Response ◽  
Log Reduction ◽  
Number Of Patients

Abstract The dose of 400mg per day of imatinib is currently considered standard therapy for patients with newly diagnosed chronic myeloid leukemia (CML) in chronic phase (CP). The IRIS trial demonstrated superior response rates in imatinib treated patients compared to interferon alfa, and evaluated molecular response up to 24 months of imatinib therapy in patients who achieved a complete cytogenetic response (CCR). Those patients with a major molecular response (MMR, ≥3 log reduction of BCR-ABL) by 12 months had 100% progression free survival at 24 months. However, very few patients had undetectable BCR-ABL levels. In the current study, we monitored the molecular response for a median of 42 months (25th to 75th percentile 39–45 months) in all patients enrolled in the IRIS trial in Australia and New Zealand who commenced imatinib as their first-line therapy (n=28 patients). We aimed to determine if the BCR-ABL levels continued to decrease and whether additional patients achieve a MMR with a longer follow up. BCR-ABL transcript levels were monitored by real-time quantitative PCR at 3 to 6 month intervals. A CCR (approximately equivalent to a greater than 2-log reduction of BCR-ABL) was achieved in 24 of the 28 patients (85%). The table demonstrates that while the frequency of achieving a MMR increased between 12 and 42 months, most of the improvement occurred between 12 and 24 months. Conversely, from 24 to 42 months the number of patients achieving a ≥4-log reduction increased significantly (P<0.001) and the median BCR-ABL levels reduced (P=0.005). Thirteen patients had a MMR by 12 months and all had a 4 log reduction at 42 months. The median log reduction from 12 to 42 months in these patients was 1.2 logs (range 0.6 to 1.8 logs). Months on Imatinib (n=patients remaining on trial) Median BCR-ABL log reduction of all patients % of all patients who achieved MMR (≥3 log reduction) % of all patients who achieved ≥4 log reduction 12 (n=26) 3.0 46 4 18 (n=26) 3.2 64 4 24 (n=26) 3.4 68 7 30 (n=26) 3.6 68 25 36 (n=25) 3.9 71 32 42 (n=24) 4.2 71 54 Undetectable BCR-ABL transcripts in our assay represent a greater than 4 to 4.5 log reduction, depending on the quality of the RNA. Ten patients had undetectable BCR-ABL on at least 1 occasion, however only 4 patients (14%) had consistently undetectable levels for more than 6 months including their last sampling timepoints (ranging from 3 to 14 consecutive analyses). Of the 4 patients without a CCR all had disease progression and in 1 patient a BCR-ABL mutation was detected, followed by rapid progression to blast crisis. Only 1 other patient had a detectable mutation. A MMR was achieved in this patient prior to detection of the mutation. The MMR was subsequently lost, as was the CCR. In conclusion, with a follow up of 42 months of imatinib therapy the incidence of achieving MMR does not appear to increase significantly after 24 months. However, among patients achieving MMR by 12 months the BCR-ABL levels continued to decline significantly, suggesting that the leukemic cell mass is still decreasing even after 3.5 years of imatinib therapy. Nevertheless very few patients have persistently undetectable BCR-ABL.

ENESTnd Update: Continued Superiority of Nilotinib Versus Imatinib In Patients with Newly Diagnosed Chronic Myeloid Leukemia In Chronic Phase (CML-CP)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 207-207 ◽  
Author(s):  
Timothy P. Hughes ◽  
Andreas Hochhaus ◽  
Giuseppe Saglio ◽  
Dong-Wook Kim ◽  
Saengsuree Jootar ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Clonal Evolution ◽  
Molecular Response ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
Free Survival ◽  
Superior Efficacy ◽  
Rate Of Progression

Abstract Abstract 207 Background: Results from the phase 3, international, randomized ENESTnd trial have demonstrated the superior efficacy of nilotinib over imatinib with significantly higher rates of major molecular response (MMR), complete cytogenetic response (CCyR), and with significantly lower rates of progression to AP/BC on treatment. Here, we present data with a median follow-up of 18 months. Methods: 846 CML-CP patients were randomized to nilotinib 300 mg twice daily (bid) (n=282), nilotinib 400 mg bid (n=281), and imatinib 400 mg once daily (n=283). Primary endpoint was MMR (≤ 0.1% BCR-ABLIS) rate “at” 12 months, as previously presented. Key secondary endpoint was durable MMR at 24 months. Other endpoints assessed at 24 months include progression to AP/BC (with and without clonal evolution), event-free survival, progression-free survival, and overall survival (OS). Results: With a median follow-up of 18 months, the overall best MMR rate was superior for nilotinib 300 mg bid (66%, P < .0001) and nilotinib 400 mg bid (62%, P < .0001) compared with imatinib (40%). Superior rates of MMR were observed in both nilotinib arms compared with the imatinib arm across all Sokal risk groups (Table). The overall best rate of BCR-ABLIS ≤ 0.0032% (equivalent to complete molecular response, CMR) was superior for nilotinib 300 mg bid (21%, P < .0001) and nilotinib 400 mg bid (17%, P < .0001) compared with imatinib (6%). The overall best CCyR rate was superior for nilotinib 300 mg bid (85%, P < .001) and nilotinib 400 mg bid (82%, P=.017) compared with imatinib (74%). The superior efficacy of nilotinib was further demonstrated using the 2009 European LeukemiaNet (ELN) 12-month milestone in which fewer patients had suboptimal response or treatment failure on nilotinib 300 mg bid (2%, 3%) and nilotinib 400 mg bid (2%, 2%) vs imatinib (11%, 8%). Rates of progression to AP/BC on treatment were significantly lower for nilotinib 300 mg bid (0.7%, P=.006) and nilotinib 400 mg bid (0.4%, P=.003) compared with imatinib (4.2%). The rate of progression on treatment was also significantly lower for nilotinib when including clonal evolution as a criteria for progression (Table). There were fewer CML-related deaths on nilotinib 300 mg bid (n=2), and 400 mg bid (n=1) vs imatinib (n=8). Estimated OS rate (including data from follow-up after discontinuation) at 18 months was higher for nilotinib 300 mg bid (98.5%, P=.28) and nilotinib 400 mg bid (99.3%, P=.03) vs imatinib (96.9%). Both drugs were well-tolerated. Discontinuations due to adverse events or laboratory abnormalities were lowest for nilotinib 300 mg bid (7%) compared with nilotinib 400 mg bid (12%) and imatinib (9%). With longer follow up there has been minimal change in the occurrence of AEs. Minimum 24-month follow-up data for all patients will be presented. Conclusions: With longer follow-up, nilotinib was associated with a significantly lower rate of progression to AP/BC on treatment and lower rates of suboptimal response or treatment failure vs imatinib. Nilotinib resulted in fewer CML-related deaths and a higher OS rate vs imatinib. Nilotinib induced superior rates of MMR, CMR, and CCyR vs imatinib in patients with newly diagnosed CML-CP. Taken together, these data support nilotinib as a new standard of care for patients with newly diagnosed CML. Disclosures: Hughes: Novartis: Honoraria, Research Funding, Speakers Bureau; Bristol-Meyers Squibb: Honoraria, Research Funding; Ariad: Honoraria. Hochhaus:Bristol Myers Squibb: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Saglio:Novartis: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria. Kim:Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. le Coutre:Novartis: Research Funding, Speakers Bureau; Bristol-Myers Squibb: Speakers Bureau. Reiffers:Novartis: Research Funding. Pasquini:Novartis: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria. Clark:Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genzyme: Honoraria, Research Funding. Gallagher:Novartis Pharma AG: Employment, Equity Ownership. Hoenekopp:Novartis Pharma AG: Employment. Haque:Novartis: Employment. Larson:Novartis: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding. Kantarjian:Novartis: Consultancy, Research Funding; Bristol Myers Squibb: Research Funding; Pfizer: Research Funding.

Fluctuating Values of Molecular Residual Disease (MRD) without Molecular Progression After Imatinib Discontinuation in Patients (pts) with Chronic Myeloid Leukemia (CML) Who Have Maintained Complete Molecular Response: Implications for Re-Treatment Criteria and Role of Prior Interferon Therapy. A Pilot Study of the French CML Group (FILMC),

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3781-3781 ◽  
Author(s):  
Philippe Rousselot ◽  
Pascale Cony Makhoul ◽  
Delphine Rea ◽  
Philippe Agape ◽  
Franck E Nicolini ◽  
...  
Keyword(s):  
Interferon Therapy ◽  
Residual Disease ◽  
Imatinib Therapy ◽  
Molecular Response ◽  
Relapse Free Survival ◽  
First Line ◽  
Free Survival ◽  
Low Levels ◽  
Sokal Score

Abstract Abstract 3781 Background. We have reported the results of imatinib discontinuation in CML pts in complete molecular response (CMR) for more than 2 years under imatinib therapy (STIM study, Mahon et al. Lancet Oncol. 2010). Among the group of pts without confirmed molecular relapse, a small proportion exhibited low levels of detectable residual disease during a prolonged period of time. Aims. In order to better characterize this phenomenon, we decided to analyse pts who stopped IM following a maintained CMR or an undetectable molecular residual disease (UMRD) and resumed therapy upon loss of major molecular response (MMR). We also aimed to validate the loss of MMR as a robust criterion for the re-introduction of tyrosine kinase inhibitors (TKIs). Patients and methods. CP-CML pts were eligible if they were in CMR (CMR4.5: BCR-ABL/ABL IS ratio <0.0032%) or UMRD (undetectable Bcr-Abl using standardized RTQ-PCR) under imatinib therapy for more than 2 years. Those pts were not enrolled in the STIM study because the study was closed or because they experienced at least one positive value of the BCR-ABL/ABL ratio during the 2 years follow-up. The proposed criterion for resuming imatinib was the loss of MMR (BCR-ABL/ABL IS ratio >0.1%). We calculated relapse free survival (RFS) using three different end-points: First loss CMR/UMRD defined by one occurrence MRD positivity; second loss of CMR/UMRD using the STIM definition (two consecutive increasing values of MRD); third loss of MMR. We also described pts with long lasting fluctuating PCR values. Results. 34 CP-CML pts were included in the analysis. Median follow-up after imatinib discontinuation was 21.3 months (2.2–83.1). Sex ratio (M/F) was 50% with a median age of 54.1 years (27.4–78.2). Sokal score distribution was 34.5%, 37.9% and 27.6% for low, intermediate and high values respectively. 19 out of 34 (55.9%) of the pts received interferon therapy prior to imatinib. Median duration of imatinib therapy and median duration of CMR/UMRD prior to discontinuation was 63.8 months (30.1–120.8) and 33.7 months (7.3–72.8) respectively (only two pts had CMR/UMRD duration less than 2 years). Of note 18 out of 34 pts (52.9%) had a least one MRD positive value after the achievement of CMR/UMRD. After imatinib discontinuation, we identified 11 pts (32.4%) who experienced repeated low levels of detectable MRD without losing their MMR. Median follow-up for these pts with fluctuating values of MRD was 15.4 months (3.5–59.5) and none of them restarted imatinib. We next analysed relapse free survival (RFS) using the loss of MMR criteria (RFS-MMR). Median RFS-MMR was not reached, compared to median RFS using the loss of CMR/UMRD criteria (4.8 months) and median RFS using the STIM criteria (13.8 months) (p=0.003). As a consequence, 62.8% of the pts remain treatment free at 2 years using the loss of MMR criteria for resuming imatinib. Fluctuating values of MRD has already been described after interferon cessation in CML interferon treated pts. We thus asked if prior therapy with interferon before imatinib may influence treatment free survival. Duration of imatinib therapy and Sokal score risk distribution were comparable between pre-treated and non pre-treated pts (p=0.7). However, the median RFS was longer in interferon pre-treated pts as compared to pts who received imatinib first line (not reached versus 7 months, p=0.047). Furthermore, this difference was not significant using the loss of CMR/URMD (p=0.27) to define molecular relapse. Conclusions. We were able to identify a significant number of pts with fluctuating values of MRD after imatinib discontinuation, a proportion underestimated in previous studies. We also validated the loss of MMR as the most accurate and robust criteria for restarting imatinib after imatinib discontinuation. Applying this criterion, we demonstrated that treatment free survival is significantly better in pts previously treated with interferon before imatinib compared to pts who received imatinib as first line therapy. An update of this pilot study on a larger number of patients will be presented. Disclosures: Rousselot: BMS, Novartis: Research Funding. Tulliez:Novartis:. Mahon:Novartis Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Honoraria; Pfizzer: Honoraria.

Detailed Investigation On Characteristics of Japanese Patients with Chronic Phase CML Who Achieved a Durable CMR After Discontinuation of Imatinib – an Updated Result of the Keio STIM Study.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2788-2788 ◽  
Author(s):  
Eri Matsuki ◽  
Yukako Ono ◽  
Koharu Tonegawa ◽  
Masatoshi Sakurai ◽  
Hiroyoshi Kunimoto ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Copy Number ◽  
Treatment Duration ◽  
Japanese Patients ◽  
The Other ◽  
Molecular Response ◽  
Imatinib Treatment ◽  
Free Survival ◽  
Number Of Patients

Abstract Abstract 2788 Background and Purpose: Tyrosine kinase inhibitor (TKI) therapy has become the standard treatment for patients with chronic myelogenous leukemia (CML). It can induce durable hematologic, cytogenetic and molecular response, leading to a marked improvement of progression-free survival (PFS). On the other hand, long-term discontinuation of TKIs has recently been investigated by many groups. Our study was designed to confirm whether TKI could be safely discontinued in Japanese patients who have maintained complete molecular response (CMR) for at least 2 years, and to identify possible factors associated with prolonged drug-free survival (DFS), including immunologic profile. The effect of imatinib discontinuation in terms of quality of life (QOL) was also assessed. Method: Adult patients with CML who have sustained CMR (defined as negative quantitative and qualitative PCR of bcr-abl in the bone marrow) for more than 2 years were enrolled in the study. Treatment with imatinib or one of the other TKIs was initiated if the peripheral blood quantitative PCR (TMA method) value exceeded 100 copies. Lymphocyte subset analysis was performed before discontinuation of the drug, and at 6 months after discontinuation or re-induction of the drug in case of relapse. In 6 patients, WT-1 specific cytotoxic T lymphocyte (CTL) frequency was also assessed before, 3 and 6 months after drug discontinuation. QOL analysis was performed using SF-36 questionnaire before, 2 months and 1 year after discontinuation of imatinib. Patients: 41 patients were enrolled in the study, among which 40 patients were analyzed. The median age of the patients was 54 (range 28 – 83) years old. The Sokal risk score was low in 24 (60%), intermediate in 10 (25%) and high in 3 (7.5%) patients. The median time on imatinib treatment was 98 (range 24–126) months and the median duration of CMR was 49.5 months (range 24–106). Results: The median follow-up of the patients at the time of this analysis was 15.5 months (range 2–18). Treatment was restarted in 18 patients (45%), and the estimated DFS rate at 12 months was 55.4% (Fig 1). In 5 patients, imatinib was commenced again, whereas 13 patients were re-treated with dasatinib. All but one patient restored CMR after commencing TKIs. Among various factors including age, previous interferon treatment, duration of imatinib treatment, duration of CMR, time until CMR, sex, cytomegalovirus serology and Sokal risk score, duration of CMR was identified as a significant factor associated with prolonged DFS on univariate analysis (p=0.027), the difference which was also significant upon multivariate analysis (p=0.014). Regarding lymphocyte subsets in the peripheral blood, no significant changes were observed in CD4, 19, 56, ab TCR, gd TCR, CD4/CD25 positive cell population, but, there was a significant increase in the proportion of CD8 positive T cells among those who relapsed and those who did not (2.4% vs −2.4%, p=0.04). There was a trend for increased proportion of WT-1 specific CTL in patients who were restarted on TKI therapy. QOL scores of both physical and mental domains did not differ significantly with the discontinuation of imatinib or re-initiation of treatment, although symptoms such as facial puffiness or muscle cramping were markedly decreased with discontinuation. There was also no difference in the patients' QOL according to the choice of drug used for re-treatment. Altogether 6 patients had fluctuating PCR copy number during follow-up, of which 2 were restarted on treatment. Others have maintained low copy number or have returned to negative during follow-up. Due to the small number of patients, no specific clinical factors or immunophenotypes associated with sustained low count PCR were identified. Conclusion: Sustained CMR was achieved in a substantial proportion of patients who had been in CMR for over 2 years. All patients restarted on TKI treatment remained sensitive to treatment. Longer time in CMR was identified as a significant factor related to sustained CMR in our patient population. Increase in CTL may also correlate with the necessity to restart treatment. Longer observation period and increased number of patients is necessary to draw a concrete conclusion, and to identify the role of immunologic profiles relative to persistence of CMR. Disclosures: No relevant conflicts of interest to declare.

Seven-year follow-up of patients receiving imatinib for the treatment of newly diagnosed chronic myelogenous leukemia by the TARGET system

2011 ◽  
Vol 35 (5) ◽  
pp. 585-590 ◽  
Author(s):  
Tetsuzo Tauchi ◽  
Masahiro Kizaki ◽  
Shinichiro Okamoto ◽  
Hideo Tanaka ◽  
Mitsune Tanimoto ◽  
...  
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Myelogenous Leukemia ◽  
Target System ◽  
Newly Diagnosed

scholarly journals Treatment Burden in Patients with Multiple Myeloma According to Comorbidity

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4775-4775
Author(s):  
Ernesto Pérez Persona ◽  
Ariane Unamunzaga Cilaurren ◽  
Ana Vega Gonzalez de Viñaspre ◽  
Itziar Oiartzabal Ormategui ◽  
Ana Santamaría Lopez ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Conflicts Of Interest ◽  
Real Life ◽  
Progression Free Survival ◽  
P Value ◽  
Treatment Burden ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Time To Death

Abstract Introduction: Over the last few years, novel agents-based combinations have been incorporated into the treatment of MM patients, particularly in relapse setting. However, these novel combinations have been evaluated in clinical trials and patients included represent a selected population. Patients in real life are usually older with comorbidities and disabilities and not allowed to be included in the trials, so, in real setting, is expected worse outcomes and shorter survival. The information about treatment burden in real life is scarce. The aim of our study was to analyze the outcome of MM patients in the real life outside clinical trials, in terms of treatment lines in a single institution setting, and to analyze the influence of comorbidities on the treatment burden. Material and methods: Medical records of MM patients treated at Txagorritxu hospital (Spain) between 2009 and January 2017 were retrospectively evaluated with the aim of mapping the course of patients as well as to investigate the factors that influence treatment-decisions at different stages of the disease. Results: 176 patients with MM were diagnosed from jan-2009 to jan-2017. Baseline patient's characteristics are presented in Table 1. The median age at diagnosis was 71 years (range 33.2-93), main of the patients where non-transplant eligible newly diagnosed MM (NTENDMM): 114 (65%). With a median follow-up of 25 months, 90.6% of newly diagnosed MM patients transplant-eligible (TENDMM) remain alive versus 65% NTENDMM patients (p value: 0.000)(figure 1). Overall, patients received a median of 2 lines of treatment, it should be noted that 86% of patients had received 3 or less lines of treatment and only 14% of the patients could receive more than 3 lines of therapy. To better evaluate treatment burden, we focused on deceased patients. At the time of analysis, 19% of TENDMM (12 patients) and 51.4% of in NTENDMM (57 patients) has died with a median time to death of 29.6 months and 18 months to death, respectively. Median lines of therapy for death patients TENDMM was 3.5 (range 1-8), with a 75 percentile of 5 lines of therapy, by contrast, death NTENDMM patients received a median of 2 lines of therapy (range: 1-6), with an 80 percentile of 3 lines of therapy (figure 2). In order to evaluate the influence of comorbidities in treatment burden for NTENDMM patients, CIRS score was estimated retrospectively. Median CIRS score was 5.5 (1-19). CIRS scale did not predict progression free survival (PFS) among the different groups: CIRS <4: 23.4 months; CIRS4-8: 25.1 months and CIRS> 8: 30.6 months (p: 0.819), however, interestingly CIRS scale predicted overall survival (OS): CIRS <4: 48 moths; CIRS4-8: 50.8 months and CIRS> 8: 12.3 months, (p: 0.012) (figure 2). Analyzing treatment burden for each CIRS score group 63% of patients with CIRS> 8 received only one line of treatment before death, compared to 39.5% and 37.5% of patients with CIRS4-8 and CIRS <4, respectively. Conclusion: Although the impressive progress in the management of relapse/refractory MM patients in recent years, half of the patients, particularly those not suitable to received an autologous transplant, will be able to received only 2 lines of treatment before dying. In fact, an adequate comorbidity assessment could select patients that will only need only one line of treatment. To the best of our known, this is the first study that correlate treatment burden according to comorbidities at diagnostic. This study could guide strategies adapted according to the comorbidity of the patients. Disclosures No relevant conflicts of interest to declare.

Imatinib Mesylate Versus Allogeneic HSCT for Patients with Chronic Myelogenous Leukemia In Accelerated Phase: A Single Center Experience In China After a 9-Year Follow-up

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2347-2347
Author(s):  
Qian Jiang ◽  
Lan-Ping Xu ◽  
Dai-Hong Liu ◽  
Kaiyan Liu ◽  
Shan-Shan Chen ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Chronic Myelogenous Leukemia ◽  
Low Risk ◽  
Myelogenous Leukemia ◽  
Imatinib Therapy ◽  
Intermediate Risk ◽  
Free Survival ◽  
Poor Risk ◽  
Risk Patients

Abstract Abstract 2347 The role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the imatinib era in patients with chronic myelogenous leukemia (CML) in accelerated phase (AP) has not been evaluated due to few comparison study published. A prospective study was designed to compare the outcome of imatinib versus allo-HSCT for AP CML according to the World Health Organization (WHO) 2001 classification in our center (Registration Number: ChiCTR-TNC-10000955). In imatinib group, imatinib were given at an initial dose of 400 mg or 600 mg daily. In allo-HSCT group, the recommended treatment prior to transplantation was a short-term imatinib therapy less than 3 months. From April 2001 to September 2008, 132 patients were enrolled, 87 in imatinib group and 45 in allo-HSCT group, respectively, according to their intention. In allo-HSCT group, 19 patients performed transplant from a HLA-matched sibling donor, 23 from a HLA-mismatched sibling/haploidentical donor, and 3 from a HLA-mismatched unrelated donor. The end time of evaluation was April 2010. After a median follow-up of 45 months (range, 7–108 months) for 53 living patients on imatinib and 65 months (range, 18–108 months) for 38 living patients post allo-HSCT, imatinib was inferior to allo-HSCT in outcome, with the estimated 6-year event-free survival (EFS), overall survival (OS) and progression-free survival (PFS) rates of 39.2% vs 71.7% (P=0.035), 51.4% vs 83.3% (P=0.023), and 48.3% vs 95.2% (P=0.000), respectively. A multivariate analysis of the total population of 132 patients adding pretreatment characteristics and therapy (imatinib versus allo-HSCT) indicated that longer CML disease duration, pretreatment anemia and higher percentage of peripheral blasts were independent adverse prognostic factors for OS and PFS in common, imatinib therapy was only associated with shorter PFS. In order to analyze whether therapy play an important role in survival differences among patients with or without common pretreatment poor prognostic factors for OS and PFS, we categorized the entire cohort into low-risk (neither factor, n=40), intermediate-risk (either factor, n=59) or poor-risk (at least two factors, n=33). Therapy had no influence on the outcome in low-risk patients, with the estimated 6-year EFS, OS and PFS rates of 80.9% vs 80.7% (P=0.898), 100% vs 81.2% (P=0.114), and 85.2% vs 95.2% (P=0.365), in imatinib group vs allo-HSCT group, respectively. EFS and OS showed no difference by therapy in intermediate-risk patients, with the estimated 6-year EFS and OS rates of 47.1% vs 61.9% (P=0.788), and 61.3% vs 81.3% (P=0.773), in imatinib group vs allo-HSCT group, respectively. However more patients developed a relapse in advanced phase with imatinib compared to those with allo-HSCT, the estimated 6-year PFS rates were 55.7% vs 92.9% (P=0.047), respectively. The superiority of allo-HSCT was extremely significant in poor-risk patients, with the estimated 5-year EFS, OS and PFS rates of 9.3% vs 66.7% (P=0.034), 17.7% vs 100% (P=0.008) and 18.8% vs 100% (P=0.006), in imatinib group vs allo-HSCT group, respectively. We conclude that allo-HSCT is the first-line option for all patients with CML in AP; it is superior to imatinib with evident survival advantage for poor/intermediate-risk patients. However, the outcome of imatinib and allo-HSCT were equally good in low-risk patients with CML in AP. For such patients, it may also be advised that imatinib remains the primary option by carefully monitoring of MRD, and allo-HSCT may be considered if there is evidence of imatinib resistance. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Deep Molecular Response in Imatinib First-Line 418 Newly Diagnosed CP CML Patients.

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3014-3014
Author(s):  
Franck Emmanuel Nicolini ◽  
Vincent Alcazer ◽  
Pascale Cony-Makhoul ◽  
Stephanie Dulucq ◽  
Sandrine Hayette ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Univariate Analysis ◽  
Molecular Response ◽  
Newly Diagnosed ◽  
First Line ◽  
Advisory Committees ◽  
Free Survival ◽  
Deep Molecular Response ◽  
Chi2 Test

Abstract Introduction Deep molecular response (DMR) are now highly desirable goals in the treatment of CP-CML, especially in the front-line setting, because it can lead to a definitive treatment-free remission (TFR). However, such a goal is difficult to attain and does not concern the majority of patients (pts), but currently the precise number of pts able to access to TFR is unknown. Aims We aim to determine the number or newly diagnosed CP-CML pts reaching DMR, stable DMR, and access to TFR, on Imatinib (IM, Glivec®) first-line. Methods We retrospectively analyzed in an observational study, a cohort of newly diagnosed CP-CML pts treated with IM first-line 400 mg daily alone in our 3 reference centers between 2000→2018. All pts were followed according to the ELN recommendations 2006, 2010 and 2013. Clinical data were extracted from medical files, and responses (hematologic, cytogenetic, molecular) were analysed according to standard methods. Molecular results were standardised according to the ELN/Eutos programs since 2003, and were all expressed as BCR-ABLIS in %. DMR have been defined according to the ELN (NCP. Cross et al., Leukemia 2015). Stability of DMR has been defined as a stable if ≥2 years at least on 4 datapoints. TFR has been proposed to pts presenting the only current recommended criteria: MR4.5 ≥2 years at least on 4 datapoints [(Rea et al., Cancer 2018)], in the 3 centers involved, within clinical trials, pioneered in our country, or now as a clinical routine recommendation. Loss of MMR was the trigger for TKI resumption after IM cessation for TFR. Overall survival (OS), progression-free survival (PFS), failure-free survival (FFS, defined as progression to advanced phases death, loss of CHR, CCyR, or MMR, discontinuation of IM for toxicity, primary cytogenetic resistance) were analysed since IM initiation in intention-to-treat. Results Four hundred and eighteen pts have been included in this study, with a median age of 60.7 (48-70) years at diagnosis, with 57% males and 43% females. Sokal score (n=401) was low in 32%, intermediate in 51% and high in 17%. ACA were present at diagnosis in 5.5% of the pts (NA in 1.44%). Major BCR transcripts were found in 98% of pts, and atypical transcripts in 1.9%. CHR was reached in a median of 1 (0.85 to 1.64) month of IM, <10% BCR-ABL transcript (IS) level at 3 months was found in 81% of the pts, and only 9.5% of pts were in MMR at 3 months. The median follow-up after IM initiation is 77.4 (0.9-231.5) months, 125 (30%) pts have switched to TKI2 for IM resistance or intolerance. Overall, 252 (60%) pts reached MR4, 127 (30%) stable MR4, 170 (41%) MR4.5, and 82 (20%) stable MR4.5. The median time on TKI necessary for obtaining stable MR4.5 is 15.6 (5.9-28) months. The cumulative incidence of MR4.5 at 12, 24, 36, 48, 60, 72, 84, 96, 108 and 120 months were 12.5%, 23.4%, 31.6%, 36.72%, 43.55%, 48.7%, 48.3%, 52.98%, 54.03%, 59.18% respectively (Figure 1A.). The cumulative incidence of stable MR4.5 at 12, 24, 36, 48, 60, 72, 84, 96, 108 and 120 months were 5.76%, 11.5%, 17.83%, 21.82%, 26.35%, 28.13%, 28.13%, 29.13%, 29.13%, 29.13% respectively (See figure 1B.). Seventeen (13%) and 10 (12%) pts have switched IM→TKI2 before obtaining a stable MR4 and a stable MR4.5 respectively. Overall, 41 (10%) pts have reached the TFR criteria and stopped their TKI and 23 (56%) never lost their MMR after cessation, with a median follow-up of 41.7 (9.4-121.8) months. In an univariate analysis, only gender (female vs male, 39% vs 61% for no MR4.5 and 53.66% vs 46.34% for stable MR4.5, p=0.028, Pearson's CHI2 test), and MMR at 3 months (yes vs no, 3.74% vs 96.26% for no MR4.5 and 17.46% vs 82.54% for stable MR4.5, p<0.001, Pearson's CHI2 test) were identified variables impacting on stable MR4.5. A multivariate analysis could not be performed on so few discriminant factors identified in the univariate analysis. Conclusions Only 42 out 418 (10%) of the newly diagnosed CP-CML pts on IM first-line in our study reach the TFR criteria we recommended, and only 22 over 418 pts (5%)will finally definitively stop any TKI durably within the limits of this retrospective observational study. Urgent strategies in order to increase the access to definitive TFR are needed. Disclosures Nicolini: Sun Pharma Ltd: Consultancy; Incyte Biosciences: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau. Cony-Makhoul:BMS: Consultancy, Speakers Bureau; Pfizer: Consultancy; Incyte: Other: Travels for attending to Congress; Novartis: Consultancy, Other: Writing support, Travels for attending to Congress. Dulucq:BMS: Consultancy; Incyte: Consultancy. Hayette:Incyte: Consultancy. Mahon:BMS: Speakers Bureau; Novartis: Speakers Bureau; Pfizer: Speakers Bureau; Incyte: Speakers Bureau. Etienne:Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Speakers Bureau; Incyte: Honoraria, Patents & Royalties, Speakers Bureau.

Preliminary Activity of Nilotinib (AMN107), a Novel Selective Potent Oral Bcr-Abl Tyrosine Kinase Inhibitor, in Newly Diagnosed Philadelphia Chromosome (Ph)-Positive Chronic Phase Chronic Myelogenous Leukemia (CML-CP).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2172-2172 ◽  
Author(s):  
Elias Jabbour ◽  
Jorge Cortes ◽  
Francis Giles ◽  
Susan O’Brien ◽  
Laurie Letvak ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Patient Choice ◽  
Myelogenous Leukemia ◽  
Molecular Response ◽  
Newly Diagnosed ◽  
Early Results ◽  
Grade 3

Nilotinib is a novel, highly selective oral Bcr-Abl inhibitor which is approximately 30-fold more potent than imatinib. High response rates with nilotinib were observed in all CML phases post imatinib failure. We evaluated the efficacy of nilotinib in newly diagnosed Ph-positive CML-CP. Thirteen patients with newly diagnosed Ph-positive CML-CP were treated with nilotinib 400 mg orally twice daily. The median age was 49 years (range, 24–72 years). The Sokal risk at pretreatment was low in 10 patients, intermediate in 2, and high in 1. The median follow-up is 8 months (range, 3–12 months). All patients have reached the 6-month evaluation. The rate of complete cytogenetic response [CGCR] (Ph 0%) at 3 and 6 months was 93% and 100%, respectively. This is compared with a CGCR at 3 months of 37% and with imatinib 400 mg/d and 61% with imatinib 800 mg/d (p=0.0002) and 54% and 85% at 6 months, respectively (p<0.0001), in historical data of newly diagnosed patients treated in studies at M. D. Anderson. Six patients were evaluable at 9 months and all were in CGCR. The median QPCR with nilotinib at 3, 6, and 9 months were, respectively, 3.4% (range, 0.02–29.5%), 1.8% (range, 0.004–9.13%), and 0.54% (range, 0.04–1.28%). At 3-month follow-up, major molecular response (BCR-ABL/ABL ratio<0.05%) was observed in 1/13 patients (8%) and in 6/11 (55%) at 6-month. Grade 3–4 myelosuppression was observed in 3 of the 13 patients and other grade 3–4 side effects in 3 patients (increased lipase in 2 and musculo-skeletal pain in 1). Four patients had their dose reduced to 400 mg daily due to extramedullary toxicity. Two patients were taken off after 6 and 8 months (patient choice) and switched to imatinib. In conclusion, early results with nilotinib 400 mg orally twice daily suggest significant efficacy manifested by complete cytogenetic responses in nearly all patients as early as 3 months after the start of therapy with a favorable toxicity profile.

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