Frequency of Complete Molecular Response In Chronic Myeloid Leukemia Patients In Real Life Practice.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1227-1227
Author(s):  
Matthieu Decamp ◽  
Dina Istasi ◽  
Atchroue Johnsonansah ◽  
Oumedaly Reman ◽  
Xavier Levaltier ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Molecular Response ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Line Therapy ◽  
Ifn Treatment ◽  
Complete Molecular Response

Abstract Abstract 1227 Introduction: Scarce data are available on the frequency of complete molecular response (CMR) in chronic myeloid leukemia (CML) patients. The European Leukemia Net defined CMR lately as an undetectable transcript quantified by Real Time PCR and/or nested PCR in two consecutive blood samples of adequate quality, using strict sensitivity criteria (sensitivity > 10 4). CMR is the best response that we can achieve in CML patients. Generally it is obtained after hematopoietic stem cell transplantation (HSCT) but since the administration of tyrosine kinase inhibitors (TKI), the number of patients seen with CMR is continuously increasing. The aim of this study is to assess the frequency of CMR in CML patients, and study their characteristics. Methods: A retrospective study was conducted to collect epidemiological, clinical, therapeutic and laboratory data of CML patients followed in hospitals of the region of Basse Normandie in France. All CML patients who had been followed up, between 1999 and 2010, by molecular monitoring for their Bcr-Abl transcript level were included. Clinical and biological responses were defined according to the ELN 2009 recommendations. Results: 199 patients were included in this study, 154 were diagnosed during the study period. Median age at diagnosis was 54 years and 46% were females. 61.3% were diagnosed in the chronic phase while the accelerated and the blast crisis phase accounted for 10.5% and 0.02%. Among these patients, 2 had the p190 BCR-ABL transcript and 2 the p230 transcript type. 169 were still followed at the end of this study and the median follow up duration was 6,4 years. Out of these 199 patients 12 died and 18 were lost out of sight. Imatinb (IM) alone or Imatinib-based combined therapies in clinical trials, was administrated as a first line treatment in 51,2% of patients. Interferon (INF) alone or in association with other chemotherapy was the frontline therapy in 37,7%; 52% of them started IFN treatment before 2000 and 73% switched to IM. At the time of analysis 26.6% of patients achieved a complete molecular response and 39.7% obtained a major molecular response (MMR) as defined by the international scale; this figure is to be tempered by the fact that the follow up duration was less than 18 months for 9,5% of patients. CMR was obtained in 11 patients following HSCT. With IM as a first line therapy, 11 patients achieved CMR or had an undetectable transcript after a median duration of 43.3 months and lasted for 13.3 months. When IM was given as a second line therapy, 17 obtained a CMR or had an undetectable transcript, in this case the median time calculated starting from the second line treatment administration was 37,3 months and in half of them, it persisted for 28 months. Among these patients, two discontinued therapy and currently they are still on CMR, 24 and 18 months after IM arrest. There was no significant difference in the median CMR achievement duration between the first and second line IM therapy groups. CMR following IFN treatment had been observed in 8 patients, 7 of them stopped IFN and have been in CMR for more than 5 years since its discontinuation. Finally five patients achieved a CMR after administration of second generation TKI. Altogether, a total of 63 patients were followed up for undetectable BCR-ABL transcript. In 53, the transcript remained undetectable; whereas 10 had lost that level of molecular response; 7 of them had regressed to a MMR though they were under IM therapy; 2 lost the MMR, one of them after IM arrest and one progressed to acute leukemia. Conclusion: A significant proportion of patients is in CMR or at least had no detectable transcript. In case of TKI therapy, the response is obtained after continuous administration (median duration was 36 months) and is durable in most cases. In this study, few patients in CMR have discontinued treatment but maintained their CMR response. Unfortunately one stopped the treatment and relapsed rapidly. The maintenance of this level of response appears to be dependent on continued suppression of the Bcr-Abl clone by TKI. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Clinical significance of dasatinib-induced pleural effusion in patients with de novo chronic myeloid leukemia

2018 ◽  
Vol 10 (3) ◽  
Author(s):  
Aya Nakaya ◽  
Shinya Fujita ◽  
Atsushi Satake ◽  
Takahisa Nakanishi ◽  
Yoshiko Azuma ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Clinical Features ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Late Onset ◽  
Molecular Response ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Treatment Agent

Dasatinib is currently approved for clinical use as a first-line treatment agent for newly diagnosed chronic myeloid leukemia (CML). However, only a few clinical trials have been performed to evaluate dasatinibinduced PE following first-line therapy. We investigated the incidence and clinical features of dasatinib-induced PE following first-line therapy in Japanese CML patients of real world clinical practice settings. Among 22 patients, the median age of PEpositive patients was higher than that of PEnegative patients. Major molecular response was achieved in 75% of PE-positive patients and 50% of PE-negative patients. Most patients developed PE more than 1 year after treatment. Appearance of PE is associated with better clinical response during dasatinib treatment, however it is developed at any time. Elderly and high-risk patients tend to develop PE. The clinical features of dasatinib-induced PE following first-line therapy might be late onset and might not immediately follow the increasing of large granular lymphocyte.

Characteristics, treatment patterns, and economic burden of patients with metastatic cervical cancer receiving systemic anticancer therapy.

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 51-51
Author(s):  
Xiaoyun Pan ◽  
Lincy S. Lal ◽  
John White ◽  
Seyed Hamidreza Mahmoudpour ◽  
Christian Valencia
Keyword(s):  
Cervical Cancer ◽  
Economic Burden ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Duration Of Treatment ◽  
Second Line Therapy ◽  
Treatment Regimens ◽  
Line Therapy

51 Background: In 2021, 14,480 patients are estimated to be diagnosed with cervical cancer in the US; 16% of patients are expected to have metastatic disease for whom the 5-year survival rate is 17.6% per SEER estimates. Patients with metastatic cervical cancer (mCC) are treated mainly with systemic therapy. This study aims to describe the clinical characteristics, demographics, treatment patterns, and economic burden of patients with mCC receiving systemic therapy. Methods: Eligible women had been diagnosed with cervical cancer, as evidenced by >2 outpatient or >1 inpatient claim in the Optum Research Database from January 2014 through January 2020. Patients were included if they had metastasis within 6 months before or after cervical cancer diagnosis, with evidence of systemic treatment on or after the latter of a claim date for cervical cancer disease or metastatic disease. The index date was the first-line treatment initiation date. Patients were required to have ≥6 months of pre-index continuous enrollment. The top 3 treatment regimens and median treatment duration by line of therapy were described. All-cause per-patient-per-month (PPPM) costs (2019 US dollars), including plan and patient paid amounts, were reported for full follow-up period from first-line and second-line therapy initiation. Results: The study sample consisted of 778 patients (mean age, 59 years; commercial, 58%; Medicare Advantage, 42%). The mean (median) follow-up period was 14 (9) months. Top baseline comorbidities were diseases of the urinary system (71%) and diseases of the female genital organs (70%), and the median Charlson comorbidity index was 7. In the first line, 80% of patients received platinum-based therapy and 23% received bevacizumab (bev). Of 778 patients, only 294 (38%) received second-line therapy, with 34% receiving bev. Top first-line treatment regimens were carboplatin + paclitaxel (27%), cisplatin (21%), and bev + carboplatin + paclitaxel (10%); the median (95% CI) duration of treatment was 3.4 (3.1-3.7) months. Top second-line treatment regimens were bev + carboplatin + paclitaxel (13%), carboplatin + paclitaxel (11%), and pembrolizumab (6%); the median duration of treatment was 3.8 (3.1-4.2) months. Mean all-cause total PPPM costs were $19,519 from first-line and $22,660 second-line therapy initiation (table). Conclusions: This study indicates that real-world mCC patients have short treatment durations and significant economic burden with first-line and second-line therapy. Novel therapies associated with greater clinical benefits in patients with mCC may provide economic benefit.[Table: see text]

Imatinib Mesylate Therapy in Late Ph+ Chronic Myeloid Leukemia Patients in Stable Complete Cytogenetic Response after Interferon-Alpha Results in a Very High Complete Molecular Response Rate.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2158-2158
Author(s):  
Giuliana Alimena ◽  
Massimo Breccia ◽  
Luigia Luciano ◽  
Fabrizio Quarantelli ◽  
Daniela Diverio ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Imatinib Mesylate ◽  
Copy Number ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Cytogenetic Response ◽  
Molecular Response ◽  
Complete Cytogenetic Response ◽  
Complete Molecular Response

Abstract Imatinib mesylate was given to 26 Philadelphia positive (Ph+) chronic myeloid leukemia (CML) patients who were in late chronic phase (CP) and in stable complete cytogenetic response (CCR) after interferon-alfa (IFN-α), but showed persistent positive residual disease at PCR analysis under this treatment. At diagnosis median age was 40 years (range 21–64) and according to Sokal’s score, 18 patients were low risk and 8 were intermediate risk. Median IFN treatment was 88 mo.s (range 15–202) and median CCR duration was 73 mo.s (range 10–148). Imatinib was administered at the standard dose of 400 mg/die, after stopping IFN for 1 week. Residual disease was measured on bone marrow (BM) cells at baseline, before starting Imatinib, at 3, 6, 12, 18 mo.s and at the last follow-up (median 32 mo.s, range 21–49), by assaying BCR-ABL transcripts using quantitative PCR (RQ-PCR). The copy number (CN) of BCR/ABL and ABL transcript were derived by the interpolation of CT values to the appropriate standard curve, and the result, for each sample, was expressed as ratio of BCR/ABL mRNA copies to ABL mRNA x 100 (normalized copy number - NCN). Imatinib treatment resulted in a progressive and consistent decline of residual disease in all but one patient, from a median of 0.89 at baseline to 0.01 at the end of follow-up. Major molecular response (BCR/ABL levels <0.1) was reached in 20 patients (77%) and BCR/ABL transcripts were undetectable in 13 (50%). Achievement of molecular response was significantly correlated with post-IFN baseline transcript level (mean 1.194 for patients achieving complete molecular response vs 18,97 for those who did not; p<0.001), but not with other clinical/biological patient characteristics. In all patients, imatinib was well tolerated with no side effects requiring drug dose reduction or dose discontinuation. Albeit obtained from an unusual subset of selected patients with favourable prognosis, and likely particularly sensitive to imatinib, present results confirm the efficacy of combining Imatinib and IFN-α and further support investigating treatment approaches employing these two drugs.

Cost-Effectiveness of Imatinib Versus Interferon-α in the Treatment of Patients Newly Diagnosed with Chronic Myeloid Leukemia, under the Brazilian Public Healthcare System Perspective.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3314-3314 ◽  
Author(s):  
Fábio Mataveli ◽  
Alessandra Calabró ◽  
Wellington Mendes ◽  
Denizar Vianna ◽  
Pedro Dorlhiac-Llacer ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Chronic Myeloid Leukemia ◽  
Adverse Events ◽  
Myeloid Leukemia ◽  
Public Healthcare ◽  
Line Treatment ◽  
Newly Diagnosed ◽  
First Line ◽  
System Perspective

Abstract The 60-month follow-up data for patients randomized to imatinib in IRIS demonstrated significant clinical improvements in survival rates and QALYs gained (17,09 years;13,58 QALYs) in patients newly diagnosed with chronic myeloid leukemia (CML) and treated with imatinib in comparison to patients under interferon-alpha (INF-α) (9,10 years;6,31 QALYS) as first line therapy. Although reimbursed as second line therapy for chronic phase CML patients who did not respond to INF-α, imatinib was not considered for public reimbursement as first line treatment in Brazil based solely on drug costs. An economic evaluation of imatinib as first line treatment versus INF-α was performed under the Brazilian Public Heathcare System perspective, according to the long-term follow-up data from IRIS, literature recommendations and prior health technology assessment from the National Institute for Clinical Excellence (NICE) to consider long term follow-up survival and adverse events costs. This study was aimed to evaluate the cost-effectiveness of imatinib compared with IFN-α for first-line treatment of chronic myeloid leukemia under the Brazilian public healthcare system perspective. For the economic model, a base case of 100 patients for each treatment option was constructed focused on drug costs and adverse events. Drug costs were estimated based on the Brazilian public healthcare reimbursement payment (APAC-SUS) for chronic phase CML treatment. Febrile neutropenia (grade III and IV), depression, nausea and abnormal liver-function results were considered as adverse events. Clinical guidelines and protocols from two public hematology Brazilian centers, Fundação Pró-Sangue FM-USP and Instituto Nacional do Cancer, were used to estimate adverse events treatment costs. Adverse events frequency for all grades was based on data published by NICE and the Agency for Health Care Research and Quality. Due to the high crossover rate from INF-α to Imatinib group observed in the IRIS study (90% from INF-α to imatinib within a year of study entry) the estimated life time survival for INF-α treatment group was based on the European Study Group on Interferon in Chronic Myeloid Leukemia. Utilities values from the IRIS study were used for both groups. Annual discount rates were of 6% for costs and 1.5% for QALYs. The annual average costs for the treatment of adverse effects in the INF-α were 1.83 higher than the imatinib group. Adverse events lifetime costs for INF-α were 24% higher than imatinib, even tough imatinib granted a projected 6.3 years survival advantage over INF-α. The resulting incremental cost-effectiveness ratio (ICER) of imatinib, compared with IFNα, considering adverse events was US$ 18,637 per QALY gained. Assuming a conservative cost-effectiveness threshold of less than US$ 25,500, which is three times the GDP per capita in Brazil (US$ 8,500 in 2005), the ICER for imatinib compared with INF-α falls within the range considered by the World Heath Organization as a cost-effective fist line treatment for patients newly diagnosed with CML.

Increasing Frequency and Marked Stability of Complete Molecular Response Is Observed in Imatinib-Treated CML Patients with Long-Term Follow Up.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 430-430 ◽  
Author(s):  
Susan Branford ◽  
John Francis Seymour ◽  
Andrew Grigg ◽  
Chris Arthur ◽  
Kevin Lynch ◽  
...  
Keyword(s):  
Chronic Phase ◽  
Leukemic Cells ◽  
Molecular Response ◽  
Second Line ◽  
First Line ◽  
Important Indicator ◽  
Complete Molecular Response ◽  
Time Point ◽  
Marked Stability

Abstract The degree of reduction of BCR-ABL in imatinib-treated patients with chronic phase CML is an important indicator of prognosis. The IRIS trial established that with first-line therapy patients with a major molecular response (MMR, 3 log reduction from a standardized baseline value for untreated patients) have a significantly more favorable progression free survival. Although 40% achieved a MMR by 12 months, very few had undetectable BCR-ABL according to strict PCR sensitivity criteria. We measured peripheral blood BCR-ABL levels by quantitative PCR at 3 to 6 month intervals in 155 patients with chronic phase CML enrolled in clinical trials of imatinib for up to 6 years. We aimed to (i) determine if BCR-ABL levels continued to decline over time, and (ii) evaluate the stability and significance of undetectable BCR-ABL. The patients included the Australasian subset of IRIS trial patients treated with 400mg of imatinib; 29 first-line patients evaluated for a median of 69 months (25th to 75th percentile range (pr) 58–72) and 24 second-line patients for a median of 54 months of imatinib (pr 38–60). 102 de-novo patients enrolled in the TIDEL trial of 600mg imatinib were evaluated for a median of 39 months (pr 30–42). Complete molecular response (CMR) was defined as undetectable BCR-ABL at a PCR sensitivity of at least 4.5 logs below the standardized baseline value confirmed on subsequent analysis after at least 3 months. The BCR control transcript level determined sensitivity and was dependent on RNA quality and reverse transcription efficiency. Of note CMR may not indicate eradication of leukemic cells, rather a reduction of BCR-ABL below the detection limit. CMR occurred in 34 patients who had 178 analyses after achieving CMR (median 4 tests per patient) and a median follow up of 15 months (pr 9–24). Very low level BCR-ABL was detected in 3 patients, the remaining 31 had undetectable BCR-ABL on every subsequent assay. Of the IRIS trial patients treated with first-line imatinib, 41% achieved a CMR by 69 months, a frequency significantly higher than occurred in these patients at 24 months (7%, p=0.006). The rate of CMR appeared to increase substantially beyond the 3 year time point (7%, 24% and 34% at 3, 4 and 5 years). 75 patients achieved MMR but not CMR and were followed for a median of 24 months after achieving MMR (pr 17–33). Six of 75 patients (8%) lost MMR as defined by &gt;2-fold rise in BCR-ABL and loss of MMR on 2 consecutive analyses. The median fold rise was 18-fold (4 to 1900-fold), of whom 1 went on to blast crisis. Four of the 6 patients had BCR-ABL mutations detected at the time of the rise and 1 of the remaining patients had duplicate Ph. MMR was lost in these 6 patients within 18 months of its achievement. The overall rate of CMR and MMR (including patients with CMR) did not differ significantly between the 3 treatment groups at the 3 year time point (CMR 7%, 8% and 18%; MMR 66%, 71% and 70% for first-line 400mg, second-line 400mg and first-line 600mg respectively). In conclusion at a median follow-up of 5.75 years of 400mg first-line imatinib, CMR was achieved in 41% of patients. Importantly, of all patients who achieved a CMR in this study using strict criteria to define the sensitivity of analysis, none have lost MMR and 91% have maintained CMR. The slow acquistion and marked stability of CMR favour the notion that the leukemic stem cell pool is steadily declining with prolonged exposure to imatinib.

Comparasion Between Nilotinib and Dasatinib as Second-Line Therapy for Patients with Chronic Myeloid Leukemia: A Single Center Retrospective Study.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3440-3440
Author(s):  
Clarisse Lobo ◽  
Carla Boquimpani ◽  
Tania Silva Madeira ◽  
Patricia Wendling ◽  
Claudia Maximo ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Second Generation ◽  
Randomized Clinical Trials ◽  
Molecular Response ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Third Line Therapy ◽  
Third Line

Abstract Abstract 3440 Nilotinib and dasatinib are second-generation tyrosine kinase inhibitors (TKI) used in patients with chronic myeloid leukemia (CML) resistant or intolerant to imatinib. There are no randomized clinical trials comparing these drugs in this context. The aim of this study was to compare, retrospectively, the hematological, cytogenetic and molecular response in patients submitted to these second-generation TKI at Hemorio, a public brazilian institution. A total of 114 patients were analyzed, 63 received nilotinib and 51 dasatinib as second-line therapy (55.3% and 44.7%, respectively). The following variables were equally distributed between these two groups (nilotinib vs. dasatinib, respectively): male sex (54% vs. 60.8%, p=0.46), median age at diagnosis (46 vs. 45 years, p=0.76), median time in months using imatinib before the switch (45.2 vs. 44.1, p=0.96), resistance to imatinib (98.4% vs. 98%, p=0.88), presence of the mutation T315I (3.2% vs. 3.9%, p=0.09), patients in chronic phase before the switch (85.7% vs. 86.3%, p=0.93). Use of another second generation TKI, as a third-line therapy, was necessary in 30 out of the 114 patients analyzed (26.1%) because of lack of response. This modification was slightly more frequent in the group initially submitted to nilotinib (31.7% vs. 19.6%, p=0.21). Patients who used a third-line therapy were excluded from response and survival analyzes. Response rates after the second-generation TKI were similar between these two groups (nilotinib vs. dasatinib): complete hematological response until three months (77.8% vs. 87.3%, p=0.24), complete cytogenetic response until six months (21.6% vs. 22.2%, p=0.95) and 12 months (32.4% vs. 33.3%, p=0.94) and major molecular response reached before 12 months (32.7% vs. 21.6%, p=0.25). Two-year overall survival (OS) and progression free-survival (PFS) were similar between these two groups (nilotinib vs. dasatinib, respectively): 92.2% vs. 87.8% (p=0.38) for OS and 87.8% vs. 83.7% (p=0.14) for PFS. Although not statistically significant, two-year OS was inferior in the group of patients who needed a third-line therapy (70.5% vs. 95.6%, p=0.70). Our results suggest that the response and survival rates are similar between nilotinib and dasatinib as second-line therapy for patients with imatinib resistant or intolerant CML. Also, they suggest an inferior prognosis for patients who need a third-line therapy. In this way, the choice between these two TKI for second-line therapy should be guided by the clinical characteristics and the mutation status of the patient. Disclosures: Lobo: NOVARTIS: Research Funding.

Impact of Second-Generation Tyrosine Kinase Inhibitors As Second Line Treatment for Patients with Chronic Myeloid Leukemia,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3780-3780 ◽  
Author(s):  
J Valentin Garcia-Gutierrez ◽  
Pilar Herrera ◽  
Lorena L Abalo ◽  
Maria Dolores Rey ◽  
Maria Calbacho ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Second Generation ◽  
Kinase Inhibitors ◽  
Salvage Treatment ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Group 2 ◽  
Group 1

Abstract Abstract 3780 Background: Imatinib has shown an outstanding improvement in the prognosis of chronic myeloid leukemia (CML) patients. Nevertheless, some of them have proven to be resistant or intolerant to imatinib. For these patients, second-generation tyrosine kinase inhibitors (TKIs) are available. These drugs may be indicated in different circumstances as primary or second resistance, suboptimal responses or intolerance.The real benefits of second-generation TKIs as salvage treatment are surely in dependence with the indication in each case and are, therefore, difficult to evaluate. Second-generation TKIs are being evaluated as first line treatment compared to imatinib with quite favourable outcomes so long, but have not yet been compared with a strategy combining imatinib followed by second-generation TKIs for patients with previous unfavourable responses. Aims: Evaluate the real benefit of second-generation TKIs in second line treatment for CML patients regardless of the indication for its use. Study groups and methods: We have studied 98 patients treated with imatinib as first tyrosin kinase inhibitor (TKI) in our centre. These patients have been classified according whether second-generation TKIs were available or not. Group 1 includes 60 patients treated since 2001 to 2005, when the only salvage treatment was an increased imatinib dose, chemotherapy or allogenic stem cell transplantation. Group 2 includes 38 patients treated since 2005 until today. In the second group second-generation TKIs (dasatinib or nilotinib) were used according to the indications mentioned above. Follow up period was 39 months and 32 months for group 1 and 2 respectively. Sokal risk index was high in 14% and 16%; intermediate 42 % and 40%; and low in 44% and 44 % for group 1 and 2 respectively. Results: The use of second-generation TKIs as second line resulted in significant benefit to patients in terms of responses. Complete cytogenetic responses (CCR) at any time were achieved in 73% and 86% for patients in group 1 and 2 (p=.09). Probability of the achievement of mayor molecular responses (MMR) was 42% vs 71% for group 1 and 2 respectively [p=.009; ratio=0.3 (0.1–0.7)]. Response rates at the last follow up for group 1 and 2 were: MMR: 33% vs 62%; CCR: 68% vs 94% and failure 32% vs 6% (p=.008). Progression free survival (including all the patients who started treatment) was 88% vs 94% for group 1 and 2 respectively. We found no correlation among responses and some prognostic factors (Sokal index, mutations at the TK domain or imatinib plasma levels). Imatinib doses were increased in 21 patients (35%) in group 1 (reasons for increasing doses were failure in 14 patients and suboptimal responses in 7 patients). 10 patients (26%) in group 2 received second-line TKIs as second line treatment (4 because imatinib failure, 3 by suboptimal responses and 3 due to intolerance). Conclussions: The use of second-generation TKIs as salvage has improved the responses of CML patients treated with TKIs. Once the second-generation TKIs has shown benefit compared to imatinib in first line treatment, this therapeutic strategy should be compared vs the use of imatinib followed of second-line TKIs for patients without optimal responses to imatinib. Disclosures: Montalban: Red Temática de Investigación Cooperativa en Cancer (RETICC): Research Funding; Asociación Española contra el Cancer: Research Funding.

Predictive Value Of Early Molecular Responses In Outcomes Of Patients With Chronic Myeloid Leukemia Treated With Imatinib In First-Line Therapy

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4941-4941
Author(s):  
Katia B. Pagnano ◽  
Bruna Vergilio ◽  
Eliana C M Miranda ◽  
Marcia Torresan Delamain ◽  
Maria Helena De Almeida ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Cytogenetic Response ◽  
Molecular Response ◽  
First Line ◽  
Molecular Responses ◽  
Advanced Phase ◽  
Significant Difference ◽  
The Impact

Abstract Several studies demonstrated the prognostic significance of an early molecular response in chronic myeloid leukemia (CML) patients (pts) treated with imatinib in first line or other tyrosine kinase inhibitors. Aims: The aim of this study was to evaluate the impact of early molecular responses, at 3 and 6 months after treatment with imatinib in CML pts and correlate these responses with CCR, MMR, overall survival (OS) and event free survival (EFS). Patients and Methods Between February 2006 and June 2012, 95  adult pts with newly diagnosed CML in chronic phase (CP) received imatinib 400mg/daily. CP was defined using WHO 2008 criteria. All pts received a short course of hydroxiurea until imatinib was available. Cytogenetic analysis was performed at diagnosis, 3, 6, 12 and 18 months after starting therapy and then every 12-24 months thereafter. BCR-ABL transcripts were measured in peripheral blood at 3-month intervals using quantitative RT-PCR (RQ-PCR). Results were expressed as BCR-ABL/ABL ratio, with conversion to the international scale (IS). Major molecular response (MMR) was defined as a transcript level ≤ 0.1% (IS). Statistical analysis: OS was measured from imatinib start until date of death or last visit. An event was defined as death from any cause. EFS was measured from imatinib start until the first event (loss of complete hematological response (CHR); complete cytogenetic response (CCR), progression to advanced phase, death or imatinib discontinuation) or last visit. OS and EFS rates were calculated using Kaplan-Meier method and log-rank test to compare its curves. The MMR probabilities according to molecular responses at 3 and 6 months were calculated by c2 method and cumulative incidence, considering as competitive event death or progression, before the event. Results 95 pts were analyzed, 57 (60%) male, with a median age of 47 years (17-79); Sokal score: high, intermediate and low was 30, 38.6 and 31.4% respectively; EUTOS scores was 81.5% low and 18.5% high. The median time from diagnosis until imatinib therapy was 1 month (0-5) and the follow-up was 39 month (3-89). Responses: 88% achieved CHR; 50% CCR and 53% MMR. One patient progressed to advanced phase during follow-up, while on imatinib treatment. 21 (22%) pts discontinued imatinib due to intolerance (47.6%); resistance (42.9%), death (4.8%) and Allo-HSCT (4.8%). At 3 months from the start of therapy, 30/64 (46.8%) achieved CCR, 15/64 (23.4%) partial cytogenetic response and 20/64 (31.2%) less than partial; by RQ-PCR, 72.3% (68/94) achieved at 3 months BCR-ABL transcripts ≤10% and 27.7% (26/94) > 10%. At 6 months 55.2% (48/87) had BCR-ABL transcripts ≤ 1% and 44.8% (39/87) >1%. The OS was 97% (95%CI: 95-99%) and EFS 63% (95%CI: 52-75%).There was no significant difference in OS and EFS in pts with RQ-PCR > 10% vs ≤ 10% at 3 months (figure 1), but pts with BCR-ABL transcripts > 10 and >1-10% at 6 months had an inferior EFS in comparison with pts with  BCR-ABL transcripts ≤ 1%  (41%,50%,89% respectively - p= 0.005), (figure 2). The CI showed that CCR pts at 3 months reached MMR earlier at 24 month (54% vs 18%, p=0.03), as well as CCR pts at 6 months, albeit no significance statistically (52% vs 37%, p= 0.16). For RQ-PCR at 3 months, pts with BCR-ABL transcripts 0-1% had a probability of 88% to achieve MMR, 1-10% had 52% and >10% 42%, p< 0.0001 (figure 3). In conclusion, our results show that early molecular responses are predictive of achieving MMR and BCR-ABL transcripts <1% at 6 months is predictive of EFS in CP-CML treated with imatinib. Disclosures: No relevant conflicts of interest to declare.

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