scholarly journals Chronic Myeloid Leukemia (CML) in Adolescents & Young Adults (AYA): Single Institution 10 Years Experience with 1st Line Imatinib Mesylate (IM)

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 6-6
Author(s):  
Hemant Malhotra ◽  
Ajay Yadav ◽  
Naveen Gupta ◽  
Satyajeet Soni ◽  
Jitender Kumar Singh ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Age Distribution ◽  
Chronic Phase ◽  
Skin Toxicity ◽  
Molecular Response ◽  
Assistance Program ◽  
Female Ratio ◽  
Male Female Ratio ◽  
Treatment Free Remission ◽  
Adult Leukemia

Introduction and Aims: CML is the commonest adult leukemia in India and the disease is diagnosed commonly in the 3rd or 4th decade of life - at least 10 years earlier than in the west, making the disease an important issue in AYA cancers. The present study reports our 10 year experience (all patients registered after 2005 with minimum of 3 years follow up) with the use of 1st line IM in patients of CML Chronic Phase (CML-CP) in patients aged 15 to 29 years. Methods: Patients of CML-CP receiving 1st line IM, aged 15 to 29 were included in the study. Standard demographics; hematological response, molecular responses (RQ-PCR on International Scale) q 6 monthly and toxicity of IM were assessed. Results A total of 337 patients of CML-CP were registered, 89 (28.7%) of which were aged between 15 to 29 and were on 1st line IM. These are reported in this study. Age distribution: 15 to 19 years: 17 (19.1%); 20 to 24: 26 (29.2%); 24 to 29: 46 (51.7%). Male female ratio: 53 (59.5%) to 36 (40.5%). Sixty one (68.5%) received innovator IM (Glivec) through the GIPAP (Glivec International Patient Assistance Program), 28 (40.5%) generic IM. At 10 years f/u, 6 (6.7%) patients were lost to f/u, 15 (16.8%) off imatinib (12 sub-optimal molecular response/relapse, and 3 b/o toxicity - 2 hepatitis, 1 renal). Seventy four (74) patients continue on IM, 56 on 400 mg/day and 18 on > 400mg/day. Fifty nine are in deep molecular response, 15 have a bcr/abl between 0.1 to 1.0 but are in complete hematological remission. Musculo-skeletal toxicity, grade I to II: 11/74 (14.8%), skin toxicity grade I: 27/74 (36.5%) and GI grade I to II: 16/74 (21.6%) were seen. Discussion and Conclusion CML is a common cancer in AYA in developing countries. IM, including generic IM, remains the standard 1st line drug for the majority and is effective, well tolerated in most patients. Issues related to treatment-free-remission (TFR), compliance, long-term drug toxicity and fertility need to be studied in this young population. Disclosures No relevant conflicts of interest to declare.

The Age of Mexican Patients with Chronic Myeloid Leukemia (CML) Ph+ Is Quite Younger Than the Reported in USA and European Series.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4291-4291
Author(s):  
Pablo Vargas-Viveros ◽  
Rafael Hurtado Monroy ◽  
Eduardo Cervera ◽  
Carlos Best ◽  
Alvaro Aguayo ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Age Distribution ◽  
Age At Diagnosis ◽  
Response To Treatment ◽  
Female Ratio ◽  
Male Predominance ◽  
Younger Age ◽  
Male Female Ratio ◽  
Long Term Observation ◽  
Mexican Patients

Abstract Abstract 4291 CML accounts for approximately 15 percent of the cases of leukemia in adults. It has an annual incidence of 1 to 2 cases per 100000, with a slight male predominance. The median age at presentation is about 60 years and the incidence increases as a function of age, as reported in North American, Australian and European series. However, in our country we found a younger age at diagnosis. Herein we report our analysis of the age distribution of the patients included in the Mexican Cooperative Leukemia Group. We analyzed 356 patients with diagnosis of CML Ph+, from January 2001 to December 2008. The data analysis showed a median age at diagnosis of 37 years (range 16 to 64 years), with a male: female ratio of 1.1:1. There is a clear difference of age between Mexican patients with CML and those reported in the referred series (37 vs. 60 years) highlighting a geographical and/or ethnical pattern that may play a role as prognostic factor and response to treatment. Moreover, challenge the multistep theory of carcinogenesis in CML, inspired by the observation that cancer incidence increases as a higher order function of age, explained by an increasing somatic mutations rate with age. Further analysis and long term observation is required. Disclosures: No relevant conflicts of interest to declare.

Comparison of Molecular Kinetics after the First and Second Imatinib Discontinuation: Results from the KID Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1920-1920
Author(s):  
Dae Young Zang ◽  
Sung-Eun Lee ◽  
Soo Young Choi ◽  
Soo-Hyun Kim ◽  
So-Young Park ◽  
...  
Keyword(s):  
Median Duration ◽  
Conflicts Of Interest ◽  
Residual Disease ◽  
Chronic Phase ◽  
Intermittent Therapy ◽  
Molecular Response ◽  
Polymerase Chain ◽  
Multicenter Prospective Study ◽  
Treatment Free Remission

Abstract Backgroud: Recent reports showing that imatinib (IM) discontinuation can be employed in patients who had enough IM therapy and undetectable molecular residual disease (UMRD) durations prior to IM discontinuation result in treatment-free remission (TFR) as a new therapeutic goal in chronic phase chronic myeloid leukemia (CP CML). Although 50-70% of patients experienced molecular relapse by several TFR studies, the most of patients resumed molecular responses (MR) following restart of IM. Through the Korean multicenter prospective study (Korean Imatinib Discontinuation Study; KID Study), we have identified predictors for sustained UMRD and explored molecular kinetics after the first IM discontinuation. In patients regaining durable UMRD with IM resumption, we tried second IM discontinuation and compared molecular kinetics between the first IM stop and second IM stop. Methods: CP CML patients who were treated with IM for more than 3 years and had undetectable levels of BCR-ABL1 transcripts determined by quantitative reverse transcriptase polymerase chain reaction (PCR) for at least 2 years were eligible for KID study and in cases of MMR loss after 2 consecutive assessments, IM treatment was re-introduced. After IM resumption for MMR loss, the molecular response was evaluated every month until MMR was re-achieved and every 3 months thereafter. The second stop was permitted in the patients who were in second UMRD for at least 2 years. Results: By the data cut-off date of 31 July 2015, among 90 non-transplant UMRD patients with at least 12 months of follow-up, 37 patients lost MMR in 2 consecutive analyses and resumed IM. Among them, 9 patients (5 men and 4 women) with a median age of 54 years (range, 35-59 years) entered into a second IM discontinuation after maintaining UMRD at least 2 years. Prior to first discontinuation, the median duration of IM therapy was 76.8 months (range, 38.5-129.0 months) and the duration of sustained UMRD was 30.1 months (range, 24.4-64.5 months). After first attempt of IM discontinuation, they relapsed after a median duration of 3.7 months (range, 1.9-20.8 months) and re-achieved UMRD at a median of 5.5 months (range, 1.8-9.4 months) after IM resumption. After sustaining a second UMRD for a median of 25.7 months, IM therapy discontinued for a second time. After a median follow-up of 37.4 months (range, 19.7-58.5 months) after second IM discontinuation, 7/9 patients (78%) and 4/9 patients (44%) lost UMRD and MMR, respectively. Among three patients who lost UMRD but not MMR, one patient showed fluctuation of BCR-ABL1 transcript under the level of 0.1% on IS for 19.5 months and two patients has not yet been followed up after a first detection of UMRD loss. Four patients who experienced second relapse (MMR loss) after a median 2.9 months (range, 2.7-3.9 months), which was similar to those of the first IM discontinuation [median 3.75 (range, 1.9-3.9 months)]. The patients who lost MMR were retreated with IM for a median of 13.6 months (range, 0.8-18.6 months); three patients re-achieved MMR at 3.5, 5.5, and 11.5 months, respectively and one re-achieved UMRD at 7.2 months. Conclusion: Our data demonstrated that a second attempt might be possible and the median time to MMR loss after second discontinuation was similar to those of the first discontinuation. But the molecular kinetics after second IM resumption needs longer follow-up with more patients. Further studies on the predictors to select patients for a trial of second TFR and novel strategies such as intermittent therapy will be warranted. Disclosures No relevant conflicts of interest to declare.

scholarly journals Ten Years of Treating Chronic Myeloid Leukemia in Rural Rwanda: Feasible Approaches for Low-Resource Settings

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4788-4788
Author(s):  
Jennifer Morgan ◽  
Jean Bosco Bigirimana ◽  
Cam Nguyen ◽  
Rebecca Deboer ◽  
Cyprien Shyirambere ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Chronic Phase ◽  
Health Systems Strengthening ◽  
Resistance Testing ◽  
Molecular Response ◽  
Assistance Program ◽  
Low Resource ◽  
Adherence To Medication

Objective: To describe the characteristics and outcomes of chronic myeloid leukemia (CML) patients treated through the Glivec Patient Assistance Program (GIPAP) in Rwanda. Methods: We retrospectively reviewed all BCR-ABL positive CML patients treated with imatinib at two rural hospitals between 2009 and 2018. Clinical data were analyzed using descriptive statistics, Kaplan-Meier method, and proportional hazards regression. Results: One hundred twenty-four patients were included; median age 35 (range: 9-81), 60% male, 88% without comorbidities. All patients presented with symptomatic disease, median duration 11 months (IQR: 4-24) and median WBC count 225.5 x 109/L (IQR: 117.7-308.5). At diagnosis, 71% were in chronic phase. On imatinib, 91% achieved complete hematologic remission (CHR); 67% within 90 days. Of those who achieved CHR, 51 (45%) lost it at some point and, of which, 36 (71%) regained CHR. At four years, overall survival was 79% (95% CI:69%-86%) for the entire cohort; 93% (95% CI: 79%-98%) for 53 patients who remained in CHR, 89% (95% CI: 69%-96%) for 34 patients who lost but regained CHR, 19% (95% CI: 1%-54%) for 12 patients who lost and never regained CHR. Never achieving CHR was associated with increased mortality (HR: 40.89; 95% CI: 9.88-169.32; p<0.001) as was losing CHR without regaining it (HR 15.73; 95% CI: 4.14-59.81; p<0.001) compared to never losing CHR. Conclusions: Here we demonstrate the feasibility of coupling molecular diagnostics with chronic targeted therapy in a rural low-resource setting through health systems strengthening and international collaboration. Our CML patients are younger, slower to achieve CHR with imatinib, and have higher rates of primary and early hematologic resistance than historical cohorts, suggesting biological differences that warrant further investigation. It is uncertain what role non-adherence to medication influences these data. Without molecular response assessment, hematologic response is an accurate marker of disease control and survival. Our imatinib failure rates highlight the need for access to resistance testing and second generation tyrosine kinase inhibitors, as well as adherence rates. Disclosures No relevant conflicts of interest to declare.

Patterns of Relapse and Toxicity in Patients of CML (Chronic Phase) on Imatinib Therapy.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4858-4858 ◽  
Author(s):  
Shyam Aggarwal ◽  
Atul Gogia ◽  
Meena Lal ◽  
Sarjana Dutt ◽  
Manorama Bhargava
Keyword(s):  
Relapse Rate ◽  
De Novo ◽  
Blast Crisis ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Imatinib Therapy ◽  
Molecular Response ◽  
Female Ratio ◽  
Long Duration ◽  
Male Female Ratio

Abstract 44 patients of CML (in chronic phase) were evaluated for their hematological, cytogenetic and molecular response (by doing quantitative PCR- for bcr-abl/abl), over a period of last 4 years. The toxicity profile of these patients was also evaluated. The mean age of study group was 54.5 years, with a male: female ratio of 1.8:1 (28 males and 16 females). 13/44 (29.3%) patients were treated with interferon prior to imatinib therapy, while the rest (31) were started on imatinib (400mg/day) upfront. 43/44 (97.7%) patients achieved a complete hematological response. 1 patient who did not respond to imatinib therapy had long duration of disease (111 months). 24/44 (54.6%) had complete cytogenetic response, 4 (9.1%) had major and 5 (11.3%) had minor cytogenetic response. 7/44 (15.9%) had hematological relapse while on Imatinib therapy. 3/44 (6.8%) had cytogenetics / molecular relapse only. Out of the 13 patients who had received prior interferon, 4 developed hematological relapse and of these 4 patients, 1 developed blast crisis and other 3 are in accelerated phase. 3/31 (9.7%) patients who received imatinib therapy upfront developed hematological relapse, while 6/31 (19.2%) developed cytogenetic/molecular relapse including the 3 patients who developed hematological relapse. A median of 17 months of imatinib therapy was given in patients who did not receive prior interferon. 36/44 (81%) developed hypopigmentation 19/44 (43%) had fluid retention, 9/44 (20%) had muscle cramps and 3/44 (6.8%) developed myelosupression. The relapse rate in patients of CML in chronic phase is more in those who have received interferon prior to imatinib therapy (37.7%). At a median follow up of 17 months the relapse rate in patients who received imatinib de novo was 19.2%.

scholarly journals Long-term outcomes with frontline nilotinib versus imatinib in newly diagnosed chronic myeloid leukemia in chronic phase: ENESTnd 10-year analysis

Leukemia ◽  
2021 ◽  
Author(s):  
Hagop M. Kantarjian ◽  
Timothy P. Hughes ◽  
Richard A. Larson ◽  
Dong-Wook Kim ◽  
Surapol Issaragrisil ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Survival Rates ◽  
Chronic Phase ◽  
Individual Treatment ◽  
Molecular Response ◽  
Newly Diagnosed ◽  
Long Term Outcomes ◽  
Treatment Free Remission

AbstractIn the ENESTnd study, with ≥10 years follow-up in patients with newly diagnosed chronic myeloid leukemia (CML) in chronic phase, nilotinib demonstrated higher cumulative molecular response rates, lower rates of disease progression and CML-related death, and increased eligibility for treatment-free remission (TFR). Cumulative 10-year rates of MMR and MR4.5 were higher with nilotinib (300 mg twice daily [BID], 77.7% and 61.0%, respectively; 400 mg BID, 79.7% and 61.2%, respectively) than with imatinib (400 mg once daily [QD], 62.5% and 39.2%, respectively). Cumulative rates of TFR eligibility at 10 years were higher with nilotinib (300 mg BID, 48.6%; 400 mg BID, 47.3%) vs imatinib (29.7%). Estimated 10-year overall survival rates in nilotinib and imatinib arms were 87.6%, 90.3%, and 88.3%, respectively. Overall frequency of adverse events was similar with nilotinib and imatinib. By 10 years, higher cumulative rates of cardiovascular events were reported with nilotinib (300 mg BID, 16.5%; 400 mg BID, 23.5%) vs imatinib (3.6%), including in Framingham low-risk patients. Overall efficacy and safety results support the use of nilotinib 300 mg BID as frontline therapy for optimal long-term outcomes, especially in patients aiming for TFR. The benefit-risk profile in context of individual treatment goals should be carefully assessed.

scholarly journals Epidemiology Data of Patients with Chronic Lymphocytic Leukemia in West Central Mexico

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5269-5269
Author(s):  
Virgina Campos-Cabrera ◽  
Gregorio Campos-Cabrera ◽  
Salvador Campos-Cabrera ◽  
Alicia Rivera-Trujillo ◽  
Sonia Hernandez-Rodriguez ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Conflicts Of Interest ◽  
Low Frequency ◽  
Epidemiological Data ◽  
Lymphocytic Leukemia ◽  
Female Ratio ◽  
Specific Protocol ◽  
Male Female Ratio ◽  
Epidemiology Data ◽  
International Data

Abstract Background: chronic lymphocytic leukemia (CLL) is a rare disease in Mexican mestizos (Br J Haematol 2015;169:909-911 and Int J Hematol 1999;69:253-255). No significant data on epidemiology is available. Methods: epidemiological data from samples referred to Laboratorios Fatima de Michoacan for flow cytometry immunophenotyping for neoplastic hematological disease. Results: 229 samples were received, 52 were diagnosed as CLL (22.7 %). Male 32 and female 20, ratio 1.6 a 1. Age from 33 to 89 years, average 66; 31 to 40 one, 41 to 50 two, 51 to 60 eleven, 61 to 70 twenty four, 71 to 80 ten, more than 81 four. Expression of CD 38 and ZAP-70 in three; only CD38 in 2, only ZAP-70 in three. Conclusions: similar results in male female ratio and age of presentation are noted as compared with international data. Low frequency of expression in CD38 and ZAP-70 may be due pre-analytic phase in the management of the sample. As a regional group we are trying to have epidemiology data in non-malignant and malignant hematological diseases to form specific protocol treatments. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Treatment-Free Remission in Chronic Myeloid Leukaemia: Can We Identify Prognostic Factors?

2021 ◽  
Author(s):  
Hilbeen Hisham Saifullah ◽  
Claire Marie Lucas
Keyword(s):  
Prognostic Factors ◽  
Chronic Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Kinase Inhibitors ◽  
Chronic Phase ◽  
Molecular Response ◽  
Predicting Success ◽  
Treatment Free Remission ◽  
Almost All ◽  
Tki Discontinuation

Following the development of tyrosine kinase inhibitors (TKI), the survival of patients with chronic myeloid leukaemia (CML) drastically improved. With the introduction of these agents, CML is now considered a chronic disease, for some patients. Taking into consideration the side effects, toxicity, and high cost, discontinuing TKIs became a goal for patients with chronic phase CML. Patients who achieved deep molecular response (DMR) and discontinued TKI, remained in treatment-free remission (TFR). Currently, the data from the published literature demonstrate that 40-60% of patients achieve TFR, with relapses occurring within the first six months. In addition, almost all patients who relapsed regained a molecular response upon re-treatment, indicating TKI discontinuation is safe. However, there is still a gap in the understanding the mechanisms behind TFR, and whether there are prognostic factors that can predict the best candidates who qualify for TKI discontinuation with a view to keeping them in TFR. Furthermore, the information about a second TFR attempt and the role of gradual de-escalation of TKI before complete cessation is limited. This review highlights the factors predicting success or failure of TFR. In addition, it ex-amines the feasibility of a second TFR attempt after the failure of the first one, and the current guidelines concerning TFR in clinical practice.

scholarly journals Incidences of Deep Molecular Responses and Treatment-Free Remission in de Novo CP-CML Patients

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2521
Author(s):  
Gabriel Etienne ◽  
Stéphanie Dulucq ◽  
Fréderic Bauduer ◽  
Didier Adiko ◽  
François Lifermann ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
De Novo ◽  
Chronic Phase ◽  
Risk Scores ◽  
Prolonged Treatment ◽  
Molecular Response ◽  
First Line ◽  
Treatment Free Remission ◽  
Tki Discontinuation

Background: Tyrosine Kinase Inhibitors (TKIs) discontinuation in patients who had achieved a deep molecular response (DMR) offer now the opportunity of prolonged treatment-free remission (TFR). Patients and Methods: Aims of this study were to evaluate the proportion of de novo chronic-phase chronic myeloid leukemia (CP-CML) patients who achieved a sustained DMR and to identify predictive factors of DMR and molecular recurrence-free survival (MRFS) after TKI discontinuation. Results: Over a period of 10 years, 398 CP-CML patients treated with first-line TKIs were included. Median age at diagnosis was 61 years, 291 (73%) and 107 (27%) patients were treated with frontline imatinib (IMA) or second- or third-generation TKIs (2–3G TKI), respectively. With a median follow-up of seven years (range, 0.6 to 13.8 years), 182 (46%) patients achieved a sustained DMR at least 24 months. Gender, BCR-ABL1 transcript type, and Sokal and ELTS risk scores were significantly associated with a higher probability of sustained DMR while TKI first-line (IMA vs. 2–3G TKI) was not. We estimate that 28% of CML-CP would have been an optimal candidate for TKI discontinuation according to recent recommendations. Finally, 95 (24%) patients have entered in a TFR program. MRFS rates at 12 and 48 months were 55.1% (95% CI, 44.3% to 65.9%) and 46.9% (95% CI, 34.9% to 58.9%), respectively. In multivariate analyses, first-line 2–3G TKIs compared to IMA and TKI duration were the most significant factors of MRFS. Conclusions: Our results suggest that frontline TKIs have a significant impact on TFR in patients who fulfill the selection criteria for TKI discontinuation.

Results of Imatinib Dose Escalation After 36 Months of Follow-up in Chronic Myeloid Leukemia Patients with Failure or Sub-Optimal Response According to 2006 EuropeanLeukemia Net (ELN) Criteria.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3302-3302
Author(s):  
Massimo Breccia ◽  
Fabio Stagno ◽  
Roberto Latagliata ◽  
Paolo Vigneri ◽  
Laura Cannella ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Dose Escalation ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Standard Dose ◽  
Acquired Resistance ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Molecular Response

Abstract Abstract 3302 Poster Board III-190 Introduction Imatinib mesylate (IM) given at a daily dose of 400 mg currently represents the gold standard of care for patients with chronic myeloid leukemia (CML) in chronic phase (CP). European LeukemiaNet (ELN) guidelines propose IM dose escalation to rescue those CML patients with either suboptimal response or drug resistance. We report on the long-term efficacy of IM dose escalation in 74 patients with CP-CML after suboptimal response or failure to IM conventional dose. Patients and methods Median age was 50 years (range 19-85), there were 52 males and 22 females. Thirteen patients were classified as hematologic failure (10 primary and 3 secondary), 57 patients as cytogenetic resistance (24 primary and 33 acquired). Three patients escalated the dose for cytogenetic suboptimal response and one patient for molecular suboptimal response at 18 months. Fifty-four received IM dose escalation from 400 to 600 mg and 20 patients from 400 to 800 mg. Results Overall, after a median follow-up of 36 months, 68/74 (91.8%) patients maintained or achieved a complete haematologic response (CHR); this was maintained in all patients who escalated the dose for cytogenetic failure or suboptimal response. A major cytogenetic response (MCyR) was achieved in 41 patients (72%) who escalated the dose for cytogenetic failure and in 6/13 (46%) patients who escalated imatinib for hematologic failure (p=0.002). Overall, complete cytogenetic responses (CCR) were achieved in 27 (37%) out of 74 CML patients: of the 13 hematologic failure patients, only 5 achieved CCyR: all patients had prior acquired resistance to imatinib. Of the 57 cytogenetic failure, 22 reached CCR: this response was obtained in 27% of the primary cytogenetic resistant, and in 50% of the acquired cytogenetic resistant patients (p=0.02). Three patients who escalated the dose for cytogenetic suboptimal response obtained CCR and complete molecular response (CMR), whereas one patient who escalated the dose for molecular suboptimal response at 18 months did not obtain CMR. Median time to cytogenetic response was 3.5 months. Cytogenetic responses occurred in 37/50 patients who escalated the dose to 600 mg and in 10/20 patients who escalated to 800 mg daily (p=0.234). CMR was obtained in 10 patients: in 7 patients who escalated the dose for cytogenetic failure and in 3 patients who escalated imatinib for suboptimal cytogenetic response. Estimated 2 year-progression free survival (PFS) and overall survival (OS) is 87% and 85% respectively. Sixteen patients (21.6%) experienced toxicities and had temporarily IM interruption. Conclusions Imatinib dose escalation can induce sustained responses in a subset of patients with cytogenetic resistance and a prior suboptimal cytogenetic response to standard-dose imatinib, whereas it appears less effective in haematologic failure patients or in molecular sub-optimal responders. The availability of second generation TKI should be taken into account in these letter categories of patients. Disclosures No relevant conflicts of interest to declare.

Impact of Imatinib Dose Escalation in Chronic Myeloid Leukemia Patients in Chronic Phase with Sub-Optimal Response or Failure with Imatinib 400 Mg.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3289-3289
Author(s):  
Katia BB Pagnano ◽  
Marcia T Delamain ◽  
Eliana C.M. Miranda ◽  
Vagner O Duarte ◽  
Brunna Eulálio Alves ◽  
...  
Keyword(s):  
Median Time ◽  
Dose Escalation ◽  
Conflicts Of Interest ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Molecular Response ◽  
Dose Increase ◽  
Free Survival ◽  
Optimal Response ◽  
Hematological Response

Abstract Abstract 3289 Poster Board III-1 Imatinib dose escalation has been used in sub-optimal response and therapeutic failure to imatinib in conventional doses. The aim of this study was to evaluate the efficacy of imatinib dose increase in CML patients in CP who did not achieve the best response to imatinib 400 mg QID. Patients and methods: All CML patients in CP treated in our institution with imatinib 400mg between March 2002 and December 2008 were evaluated. Imatinib was escalated to 600–800mg in cases with sub-optimal response or failure, according to Leukemia Net or IRIS Trial criteria. All survival curves were calculated from date of dose increase: overall survival (OS) until death or last follow-up, event free survival (EFS) until loss of complete hematological response (CHR) or major cytogenetic response (MCyR), progression to accelerated phase (AP) or blast crisis (BC) or death from any cause. Transformation free survival (TFS) was calculated from dose increase until progression to AP, BC or death. Results: 137 patients in CP were treated with imatinib 400 mg. Dose was escalated in 55 (40%) patients due to loss or failure to achieve CRH (13 = 24%); progression to BC (2 = 3.5%); no CCR (11 = 20%); loss of RCC (5 = 9%); CCR without major molecular response (MMR) after 18 months of imatinib (24 = 43.5%). Males: 37, females 18 cases. Median age: 44 (16–74) years. Twenty-eight patients (49%) were treated with imatinib as first line therapy and 51% had used IFN previously. Median time between diagnosis and imatinib start was 4.5 (0–94) months. Responses: 94% achieved CHR; 58% CCR and 34% MMR. After dose increase, 31 (56%) responded: 58% of the patients with previous sub-optimal molecular response achieved MMR. Among those who benefited from dose increase, only 3 cases lost the response: one with hematological resistance and two with cytogenetic resistance (2 lost CCR and one CHR). Seven out of 16 patients who increased dose due to cytogenetic failure (loss of response, failure and sub-optimal response) achieved response: one had partial cytogenetic response (PCyR) and 6 CCR. Five patients with hematological failure presented response: CHR (2), CCR (1), PCyR (1) and MMR (1). Patients with BC (2 cases) did not respond to dose escalation. TFS was 89% and 67% in 2 and 5 years, respectively. EFS was 71% and 64% in 2 and 5 years respectively. When stratified by the type of failure, EFS was 100%, 49% and 34% in the group with molecular sub-optimal response with median time of 22 (4–41) months, cytogenetic 17 (1.2–42) and hematological failure 7.7 (0.2–57), respectively (P<0.03). Conclusions: imatinib dose escalation was successful in molecular sub-optimal response. However, the patients who do not achieve MMR might be candidates to second line treatment. Patients who did not achieve cytogenetic or hematological response did worse with imatinib dose escalation. Disclosures: No relevant conflicts of interest to declare.

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