Treatment Response Patterns and Related Prognostic Indicators in Chronic Myeloid Leukemia (CML) Patients: A Multi-Country Medical Record Review Study

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3131-3131
Author(s):  
Peter C Trask ◽  
Debanjali Mitra ◽  
Shrividya Iyer ◽  
Sean D Candrilli ◽  
James A. Kaye
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Medical Records ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Prognostic Indicators ◽  
Black Race ◽  
Line Therapy ◽  
Sokal Score ◽  
Line Of Therapy ◽  
The Uk

Abstract Abstract 3131 Objective: To assess treatment responses and prognostic indicators of response among patients with chronic myeloid leukemia (CML) in multiple countries. Methods: Physicians in United States (N=60), United Kingdom (N=45), Germany (N=49), and Japan (N=60) were recruited to abstract data retrospectively from medical records of patients diagnosed with CML between 1/1/2005 and 12/31/2009. Patients selected were age ≥18 years and in chronic phase at the time of diagnosis and were Philadelphia chromosome and/or BCR-ABL positive. Patients were also required to have received 1st-line treatment with imatinib and not be enrolled in a randomized clinical trial during the study period. We included a subgroup who had also received 2nd-line therapy with nilotinib or dasatinib. We assessed rates of complete hematological response (CHR) at 3 months (mos), complete cytogenetic response (CCyR) at 12 mos, and complete or major molecular response (MMR) at 18 mos, stratified by line of therapy. We used multivariable logistic regression models to evaluate the independent prognostic effects of age, gender, Sokal score, spleen size, race, Charlson comorbidity index score (CCIS), dose, and time to initiation of therapy. For patients on 1st line therapy, only those in chronic phase at the time of imatinib initiation and with non-missing data on the variables of interest (n=751) were included in the regression analyses. Results: Data were abstracted from medical records of 1, 063 patients in US (N=300), Japan (N=300), Germany (N=243), and in the UK (N=220). The average patient age was 55 years and a majority were male (60%). Response rates by line of therapy are listed in Table 1. The proportion of patients achieving 1st-line response was similar across countries except that a greater percentage of patients from the UK obtained CHR at 3 mos (70.5%) compared to other countries (range: 46% [US] to [50.6% [Germany]) and MMR at 12 mos (55%) compared to the other countries (range: 26% [Japan] to 40% [Germany]). In 1st-line therapy, age ≤45 years (odds ratio [OR]=1.57, 95% CI=1.05–2.33 reference [ref] age 45–65) and low Sokal score (OR=1.64, 95% CI=1.16–2.33; ref intermediate) were associated with a greater likelihood of CHR response at 3 mos while Black race (OR=0.40, 95% CI=0.16–0.98; ref White race) and a CCIS score of 2 or higher (OR=0.48, 95% CI=0.25–0.75; ref: CCIS 0) were associated with a lower likelihood of CHR response at 3 mos. Age ≤45 years (OR=1.49, 95% CI=1.02–2.17) and Black race (OR=0.33, 95% CI=0.14–0.77) had similar associations with CCyR at 12 mos as for CHR at 3 mos. We did not find any significant prognostic indicators of MMR at 18 mos. In 2nd line therapy, choice of dasatinib as the 2nd-line drug (OR=2.77, 95% CI=1.19–6.43; ref: nilotinib), CHR to 1st-line therapy (OR=5.97, 95% CI=1.72–20.71; ref: no CHR), and low Sokal score (OR=7.93, 95% CI=2.93–21.51) were indicative of higher likelihood of CHR. Treatment with dasatinib (OR=7.43, 95% CI=2.36–23.40) and initial dose > 100mg for dasatinib or 600mg for nilotinib (OR=3.25, 95% CI=1.11–9.51; ref: dose ≤ 100mg for dasatinib or ≤ 600mg for nilotinib) predicted a greater likelihood of CCyR at 12 mos. We found no variables prognostic of MMR at 18 mos. Conclusions: We found several factors in addition to Sokal score to be prognostic for clinical response in 1st-line therapy, including younger age, White race, and no comorbidity. In addition, in 2nd-line therapy, the likelihood of response was higher in patients treated with dasatinib than in those who received nilotinib. To our knowledge, this difference has not been reported previously and could reflect a real difference in outcomes. However, it may also be due to residual confounding by factors that we could not control in a retrospective observational study. Disclosures: Trask: Pfizer: Employment. Mitra:Pfizer: Consultancy. Iyer:Pfizer: Employment. Candrilli:Pfizer: Consultancy. Kaye:Pfizer: Consultancy.

scholarly journals Efficacy of Ponatinib after Multiple Lines of Therapy for Chronic Myeloid Leukemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3013-3013
Author(s):  
Mahesh Swaminathan ◽  
Hagop M. Kantarjian ◽  
Koji Sasaki ◽  
Farhad Ravandi ◽  
Gautam Borthakur ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Median Time ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Molecular Response ◽  
Genetics Research ◽  
Line Therapy ◽  
Line Of Therapy

Abstract Background: Ponatinib, a third-generation pan-tyrosine kinase inhibitor (TKI), was found to be effective in heavily pretreated patients (pts) with chronic myeloid leukemia (CML). With the availability of multiple TKI, these agents are used in different sequences, and there is limited information on the value of various TKI in different lines of therapy. Since ponatinib has been effective in 3rd and subsequent lines of therapy, we performed an analysis of a cohort of pts with CML who received ponatinib as a different line of treatment. Method: A total of 80 pts with chronic phase of CML and received ponatinib from 2009 to 2018 were analyzed. Only pts who received ponatinib as a second or subsequent line of therapy of CML were included. Major cytogenetic response (MCyR), complete cytogenetic response (CCyR), major molecular response (MMR), molecular response (MR) 4, and MR 4.5 were assessed. Event-free (EFS), transformation-free (TFS), failure-free (FFS) and overall survival (OS) were also analyzed. Results: Nine pts (11%) received ponatinib as a 2nd line therapy (prior TKI imatinib in 6, dasatinib in 1, and nilotinib in 2 pts); 21 (26%) as a 3rd line, 26 (33%) as a 4th line, and 24 (30%) as a 5th and above line. The median age was over 50 years (Y) in all the groups except for pts who received ponatinib as a 3rd line [38 Y (23-76)]. Among pts who received ponatinib as 2nd line, 9 (100%) achieved CCyR and MR 4.5; the median time to achieve CCyR and MR 4.5 was 3 and 6.8 months (mo), respectively (Table 1). In pts treated in 3rd line CCyR and MR 4.5 were 67% and 57%, respectively and the median time to response was 4.8 and 19.3 mo, respectively. Of the 26 pts treated in 4th line, 13 (50%) achieved CCyR (median time to CCyR 3 mo) and 7 (27%) achieved MR 4.5 (median time 11.6 mo). In 5th line and above 14 (58%) achieved CCyR (median time 6.4 mo) and 8 (33%) achieved MR 4.5 (median time 12.3 mo) (Figure 1). After a median follow-up of 59.8 months (range, 4.7 to 114.3) for all pts, the median OS was not reached in pts treated in 2nd to 4th line and 81.4 mo in ≥5th line. The median FFS was not reached in 2nd line, and was 45.6, 20.2, and 17.8 mo in 3rd, 4th, and ≥5th line, respectively. The median EFS and TFS was not reached in any line of treatment. The TFS was significantly better in pts who received ponatinib as a 2nd-4th line therapy as compared to ≥5th [p=0.0026, HR-55.97 (4.076-768.7)] (Figure 2). Conclusion: Our results suggest that CCyR and MR 4.5 were higher when ponatinib was used in up to 4th line of therapy for resistant CML, and it was particularly effective in 2nd or 3rd line where high rates of MR4.5 can be achieved. These results underscore the efficacy of ponatinib in these settings. Disclosures Sasaki: Otsuka Pharmaceutical: Honoraria. Ravandi:Jazz: Honoraria; Macrogenix: Honoraria, Research Funding; Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Seattle Genetics: Research Funding; Seattle Genetics: Research Funding; Abbvie: Research Funding; Jazz: Honoraria; Xencor: Research Funding; Astellas Pharmaceuticals: Consultancy, Honoraria; Orsenix: Honoraria; Sunesis: Honoraria; Abbvie: Research Funding; Amgen: Honoraria, Research Funding, Speakers Bureau; Astellas Pharmaceuticals: Consultancy, Honoraria; Sunesis: Honoraria; Orsenix: Honoraria; Macrogenix: Honoraria, Research Funding; Xencor: Research Funding; Amgen: Honoraria, Research Funding, Speakers Bureau. Kadia:Takeda: Consultancy; Jazz: Consultancy, Research Funding; Celgene: Research Funding; Novartis: Consultancy; Celgene: Research Funding; Takeda: Consultancy; Abbvie: Consultancy; Novartis: Consultancy; Jazz: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; BMS: Research Funding; Pfizer: Consultancy, Research Funding; Abbvie: Consultancy; BMS: Research Funding; Amgen: Consultancy, Research Funding; Amgen: Consultancy, Research Funding. DiNardo:Agios: Consultancy; Bayer: Honoraria; Medimmune: Honoraria; Karyopharm: Honoraria; Celgene: Honoraria; Abbvie: Honoraria. Konopleva:Stemline Therapeutics: Research Funding; abbvie: Research Funding; cellectis: Research Funding; Immunogen: Research Funding. Pemmaraju:stemline: Consultancy, Honoraria, Research Funding; cellectis: Research Funding; novartis: Research Funding; samus: Research Funding; plexxikon: Research Funding; daiichi sankyo: Research Funding; celgene: Consultancy, Honoraria; Affymetrix: Research Funding; SagerStrong Foundation: Research Funding; abbvie: Research Funding. Daver:ARIAD: Research Funding; BMS: Research Funding; Novartis: Research Funding; Incyte: Consultancy; Incyte: Research Funding; Karyopharm: Research Funding; Kiromic: Research Funding; Pfizer: Research Funding; Daiichi-Sankyo: Research Funding; Sunesis: Research Funding; Alexion: Consultancy; ImmunoGen: Consultancy; Karyopharm: Consultancy; Otsuka: Consultancy; Novartis: Consultancy; Pfizer: Consultancy; Sunesis: Consultancy. Wierda:Genentech: Research Funding; AbbVie, Inc: Research Funding. Jabbour:novartis: Research Funding. Cortes:novartis: Research Funding.

Recurrent bone marrow aplasia secondary to nilotinib in a patient with chronic myeloid leukemia: A case report

2012 ◽  
Vol 18 (4) ◽  
pp. 440-444 ◽  
Author(s):  
Prathima Prodduturi ◽  
Anamarija M Perry ◽  
Patricia Aoun ◽  
Dennis D Weisenburger ◽  
Mojtaba Akhtari
Keyword(s):  
Bone Marrow ◽  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Chronic Phase ◽  
Bone Marrow Aplasia ◽  
Line Therapy ◽  
Grade 3

Nilotinib is a potent tyrosine kinase inhibitor of breakpoint cluster region-abelson (BCR-ABL), which has been approved as front-line therapy for newly diagnosed chronic myeloid leukemia in chronic phase and as second-line therapy after imatinib failure in chronic or accelerated phase chronic myeloid leukemia. Tyrosine kinase inhibitors have been associated with myelosuppression and grade 3 or grade 4 cytopenias are not uncommon in chronic myeloid leukemia patients treated with these drugs. There are a few reports of imatinib-associated bone marrow aplasia, but to our knowledge only one reported case of bone marrow aplasia associated with nilotinib. Herein, we report a 49-year-old male patient with chronic phase chronic myeloid leukemia, who developed severe bone marrow aplasia due to nilotinib. Possible mechanisms for this significant adverse drug reaction are discussed along with a review of literature.

scholarly journals Nilotinib first-line therapy in patients with Philadelphia chromosome-negative/BCR-ABL-positive chronic myeloid leukemia in chronic phase: ENEST1st sub-analysis

2017 ◽  
Vol 143 (7) ◽  
pp. 1225-1233 ◽  
Author(s):  
Andreas Hochhaus ◽  
Franҫois-Xavier Mahon ◽  
Philipp le Coutre ◽  
Ljubomir Petrov ◽  
Jeroen J. W. M. Janssen ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

A Decade Of Imatinib As First-Line Treatment Of Chronic Myeloid Leukemia: A Single - Latin American Institution Experience

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5194-5194
Author(s):  
Alvaro Cabrera Garcia ◽  
Carolina Balderas Delgado ◽  
Juan Julio Kassack Ipiña ◽  
Christian Omar Ramos Peñafiel ◽  
Juan Collazo Jaloma ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Latin American ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Hematologic Toxicity ◽  
Line Treatment ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Eutos Score

Abstract Targeted therapy commenced against Chronic Myeloid Leukemia (CML) with the development of small-molecule tyrosine kinase inhibitors (TKIs), since its approval in 2001 as first-line therapy, imatinib has been effective in achieving high response rates and improving the prognosis. However, the excellent results of large clinical trials are not entirely reproducible in the “real world”, we want to share our experience of a decade of use as front-line treatment. A total of 160 patients with previously untreated CML since 2002 were reviewed: 90% chronic phase (CP), 7% accelerated phase (AP), and 3% blast phase (BP). All were treated with standard-dose imatinib. In CP, overall survival (OS) at 75 months was 82% and progression-free survival 66%(PFS). Survival was worse in those over 60 years (P= < .001). 40% achieved and maintained Complete Cytogenetic Response (CCyR), 19 patients progressed to BP. 23.4% had some degree of hematologic toxicity that required a temporary suspension or reduction of the initial dose. 26.8% of patients with chronic phase treated at our institution were in the high EUTOS score. In this population, the EUTOS score was not predictive for outcome. Our study showed that imatinib is effective, and well tolerated by our patients and remains as a good strategy used as first-line therapy for patients with CML. Disclosures: No relevant conflicts of interest to declare.

Efficacy Of Different Therapeutic Approaches In Blastic Phase Of Chronic Myeloid Leukemia: Single Centre Experience

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5173-5173
Author(s):  
Elza Lomaia ◽  
Ekaterina Romanova ◽  
Larisa Girshova ◽  
Yulia Alexeeva ◽  
Eugenia Sbityakova ◽  
...  
Keyword(s):  
Overall Survival ◽  
Chronic Myeloid Leukemia ◽  
Median Time ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Chronic Phase ◽  
Molecular Response ◽  
Line Therapy ◽  
Advanced Phase ◽  
Blastic Phase

Abstract Dramatic changes in overall survival of patients (pts) with chronic myeloid leukemia (CML) in chronic phase (CP) have occurred since tyrosine kinase inhibitors (TKIs) were implemented in the treatment strategy. But there are still many issues in therapy of advanced phase disease, especially in blastic phase (BP). Allogeneic stem cell transplantation (alloSCT) is still the only curative option for CML BP, so all efforts should be focused on bringing pts to alloSCT. Thus optimal approach to obtain at least stable hematologic response before alloSCT is needed. Since 2008, 14 pts (4 more pts with isolated extramedullary BP were not included) with CML BP were admitted to our clinic. These were 8 males and 6 females with a median age of 44 years (range; 21-63) at the time of BP. The types of BP were: biphenotypic (n=1), undifferentiated (n=1), myeloid (n=8) and lymphoid (n=4). All pts except 2 (1 with BP and 1 with accelerated phase) were initially diagnosed as CP. Median time from diagnosis to BP was 37 months (range; 0-83). Before BP all pts except 2 were pretreated with imatinib and 6 of them, after failing imatinib, received one or more new TKIs. First line therapy in BP was monotherapy with new TKI (n=5) or chemotherapy (“7+3”, “RACOP”, low doses of Ara-C, “Hyper-CVAD”, “Dexa+VCR”) with or w/o TKI (n=9). Responses are specified in table 1. FLAG regimen was subsequently given to 5 pts as second or more line therapy after failure of previous monoTKI (n=1) or Rx + TKI (n=4). Median time from BP to FLAG was 3,5 months (range; 1,5-21). The best response to FLAG therapy was complete hematologic (n=1), complete cytogenetic with (n=1) or w/o (n=1) major molecular response. There were no responses in 2 cases. All responders maintain their response after median follow up (FU) of 2 months (range; 1,5-5). All patients treated with FLAG are alive (2 after alloSCT, 3 pending alloSCT). Only 1 ptn reached alloSCT w/o any Rx after monoTKI. AlloSCT was successful in 4/5. Median FU time for patients alive after alloSCT is 12 months (range; 3,5-25). For whole group after a median FU of 14 months, 7/14 (50%) pts are alive, including 4 pts after alloSCT. Estimated 3-year overall survival for all pts is 54% (fig. 1). Conclusion All CML BP patients treated with TKIs alone lost their response in a short time. Responses were much more durable in pts treated with Rx +/- TKIs. FLAG regimen was effective even in pts with failure to previous Rx+TKIs. The majority of pts after alloSCT are alive. Chemotherapy, including FLAG with concomitant or subsequent TKIs, had advantage over monoTKI both in overall and progression free survival in CML BP. Disclosures: Lomaia: Novartis: Honoraria, Travel grants Other; Bristol-Myers Squibb: Honoraria, Travel grants, Travel grants Other. Zaritskey:University of Heidelberg: Research Funding.

scholarly journals Krónikus myeloid leukaemiás betegek követése a Marosvásárhelyi Hematológiai és Csontvelő-átültetési Klinika beteganyagában 2008 és 2018 között

2019 ◽  
Vol 160 (2) ◽  
pp. 67-72
Author(s):  
Aliz-Beáta Tunyogi ◽  
Erzsébet Lázár ◽  
István Benedek jr. ◽  
Johanna Sándor-Kéri ◽  
Annamária Zsigmond ◽  
...  
Keyword(s):  
Overall Survival ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Chronic Phase ◽  
Cumulative Probability ◽  
Close Monitoring ◽  
Molecular Remission ◽  
Risk Patients ◽  
Sokal Score

Abstract: Introduction and aim: Chronic myeloid leukemia is a clonal myeloproliferative disorder characterized by the BCR-ABL gene rearrangement with translocation between chromosomes 9 and 22. The constitutively active BCR-ABL tyrosine kinase inhibitor became the standard frontline therapy. The molecular monitoring is essential. Method: We studied the chronic myeloid leukemia patients at the Clinical Hematology and Bone Marrow Transplant Unit Tg-Mures between 2008 and 2018. Results: We followed 59 patients, median age of 45 years, female : male ratio 1.5 : 1. 80% of the patients were in chronic phase. Sokal score was low in 61%, intermediate 27% and high in 12% of the patients. The median follow-up time was 5 years and 9 months. 59% of the patients reached molecular remission (average time 11 months). The cumulative overall survival was 80% at 5 years and 76% at 10 years. The overall survival according to disease phase was 98%, 85%, 20%; according to Sokal score it was 91%, 66%, 51%. The cumulative progression-free survival was 75% at 5 years and 50% at 10 years. Only 8% of the low risk patients are progressing opposite to 77% of the high risk patients. The cumulative probability to maintain the molecular remission for 5 years is 100%, for 10 years 91% and for 15 years 52%. Conclusion: A rising level of BCR-ABL is an early indication of the loss of response identifying the patients who need close monitoring and therapeutic change. Orv Hetil. 2019; 160(2): 67–72.

Infectious Events In Patients with Chronic Myeloid Leukemia Treated with Nilotinib as a Front Line Therapy and After Imatinib Failure

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1233-1233 ◽  
Author(s):  
Ali M Al-Ameri ◽  
Jorge E. Cortes ◽  
Hagop Kantarjian ◽  
Elizabeth Burton ◽  
Alfonso Quintas-Cardama ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Fungal Infections ◽  
Therapy Group ◽  
Chronic Phase ◽  
Infectious Complications ◽  
Front Line ◽  
Line Therapy ◽  
Group 6

Abstract Abstract 1233 Background: Different tyrosine kinase inhibitors have different effect on various kinases. Dasatinib and bosutinib inhibt Src, an effect that has been suggested could have an immunosuppressive effect. Others, such as imatinib and nilotinib, have no discernible effect on Src. All agents however can cause myelosuppression. Because of these effects, and in view of long-term us of these agent, infectious complications may occur during therapy. The risk of infectious complications with nilotinib therapy has not been reported. Aim: To investigate the frequency and characteristics of infectious events in patients (pts) with chronic myeloid leukemia (CML) treated with Nilotinib as a front line therapy (FL) or after Imatinib failure (IF). Methods: Retrospective review of medical records of patients who received Nilotinib between Jun 2004 and Jun 2010, either as FL therapy or as salvage therapy after IF. Results: The total number of pts treated were 169, including 90 FL pts and 79 IF pts. Overall, 132 pts (78%) were in chronic phase and 37 pts (22%) were in accelerated phase. The median age was 53 (20 - 87) years and 57% of the pts were male. Median follow up for all patients was 30 months. Among the FL therapy group, 9 (10%) pts developed any infection, whereas 29 of 79 (37%) pts treated with nilotinib after IF developed any infection. Table 1 shows the types of infections for both groups. Of the 43 infections in the IF group, 26 (60%) were clinically documented infections (CDI), 8 FUO (19%), 3 bacterial (7%), 5 viral (12%) [Zoster (2), influenza (2), RSV (1)] and 1 (2%) fungal infections. Nine (21%) of these infectious episodes occurred with neutropenia and 24/43 episodes (56%) required hospitalization. In the FL group, 6 (60%) of the events were CDI, 2 (20%) were FUO, 1 (10%) was bacterial and 1 (10%) was viral [zoster]. None of the FL group events were associated with neutropenia and only 2/10 episodes required hospitalization. We also studied the relationship of infectious events according to the nilotinib doses at the moment of the infection. In IF group, 46% of the events occurred at 800mg/day, 30% at 400mg/day, 14% at 1200 mg/day and 10% at 200mg/day or less. In the FL group, 6 (60%) events occurred at 800mg/day and 40% at 400mg/day. There was no statistically significant association between infectious event rate and the nilotinib starting dose. Overall mortality at 30 months was 22% (29/169), 35 (44%) of the IF group died and 2 (2%) of the FL died. Three of the deaths in the IF group and none in the FT group were due to infection. Conclusions: Although several patients developed infectious complications during nilotinib therapy, particularly when used after imatinib failure, these episodes were common infections that responded rapidly to adequate intervention. Atypical infections were not seen. Further research is needed to determine predisposing factor and measures to prevent infections. Disclosures: Cortes: Novartis: Research Funding; BMS: Research Funding; Pfizer: Research Funding; Pfizer: Consultancy. Kantarjian:BMS, Pfizer and Novartis: Research Funding; Novartis: Consultancy. O'Brien:Novartis: Research Funding; BMS: Research Funding.

Results of Imatinib Therapy In Patients with Early and Late Chronic-Phase Chronic Myeloid Leukemia In a South Brazilian Cohort.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4487-4487
Author(s):  
Marcelo Capra ◽  
Mariza Shaan ◽  
Katia Fassina ◽  
Mario Sérgio Fernandes ◽  
Marco Antônio Schilling ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Molecular Response ◽  
Imatinib Treatment ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Sokal Score ◽  
Hasford Score

Abstract Abstract 4487 Background: Imatinib treatment for Chronic Myeloid Leukemia (CML) was first introduced in Brazil in 2001, initially used as second line therapy for patients resistant or intolerant to interferon (IFN). In 2008 imatinib was adopted as front-line therapy for chronic-phase (CP-CML) and clinical experience is improving since then, but little is known about the result of its introduction in our clinical practice. Aims: To evaluate the impact of imatinib treatment in the outcomes of a cohort of CP-CML and the prognostic significance of Sokal and Hasford scores and late-onset treatment. Methods: We conducted a retrospective study in a cohort of patients with CP-CML from a south Brazilian database. All patients received imatinib 400mg as first or second-line therapy. Patient evaluation and response criteria followed the European LeukemiaNet. The outcomes were response to treatment, event-free survival (EFS) and overall survival (OS). Results: We analyzed data from 185 pts with CP-CML diagnosed since 1990. The median age at diagnosis was 48 years (4 – 85). The median time from diagnosis to imatinib was 7 months (0 – 178) and 29% of pts had more than 12 months lapse. Prior therapy with IFN was used in 70% pts. All pts had a minimum follow-up of 12 months. At baseline, 57 pts (31%) were in complete hematological response (CHR) due to the use of previous treatment. Of the 127 pts not in CHR at baseline, 98% achieved CHR early during imatinib treatment. 177 pts had cytogenetic evaluation during treatment and 9 pts were in complete cytogenetic response (CCyR) due to the use of previous IFN. Of the 168 pts not in CCyR at baseline, 86,4% achieved a major cytogenetic response (MCyR) during imatinib treatment (84% had a CCyR and 2,4% had a partial cytogenetic response). The rate of pts achieving MCyR any point during treatment differed significantly in the low, intermediate and high risk Sokal score groups (97%, 81% and 78% respectively, P=0,04), but not in the Hasford score groups (90%, 85% and 72%, P=0,22). Minor cytogenetic response was seen in 3,6% of pts, minimal cytogenetic response in 6% and 9,5% had no cytogenetic response. The median time to a MCyR was 9 months, with 62% of pts achieving MCyR at 12 months. The rate of pts achieving MCyR in 12 months differed significantly between pts who start imatinib before 12 months from diagnosis (68%) and those late treated (47%, P=0,02). Evaluation of minimal residual disease at the molecular level was available for 155 pts: 25,5% of pts had a complete molecular response (CMR), 43% had a major molecular response (MMR) and 2 pts were in MMR at baseline due to previous IFN. The projected EFS and OS rates at 4 years were, respectively, 68% and 92% after a median follow-up time of 4 years. The rate of EFS differed significantly in the low, intermediate and high risk Sokal score groups (80%, 66% and 52% respectively, P=0,04), but not in the Hasford score groups (78%, 62% and 44%, P=0,09). During treatment with imatinib, 120 pts (65%) had a register of any grade hematologic adverse event (21% being grades 3 or 4) and 165 pts (90%) had a register of any grade nonhematologic adverse event (9,3% being grades 3 or 4). Of the 185 pts who received treatment, 134 (72%) continue to receive imatinib and 51 (28%) discontinued treatment. The reasons for discontinuation were: 11 (6%) pts had drug-related adverse events (3 [1,6%] hematologic and 8 [4,3%] nonhematologic), 17 (9,2%) had disease progression (5 [2,7%] loss of CHR, 10 [5,4%] loss of CCyR, 2 [1%] had progression to accelerate or blastic phase), 22 (11,9%) had treatment failure (3 [1,6%] had no CHR, 13 [7%] had no CCyR and 6 [3,2%] had no MMR), 1 pt (0,5%) discontinued due to comorbidity. For the 51 (100%) pts that discontinued imatinib, 31 (61%) switched to dasatinib, 17 (33%) to nilotinib, 1 (2%) to hydroxyurea, 1 (2%) to other treatment and 1 (2%) remained without treatment. Sixteen pts (8,6%) died during imatinib treatment or during long-term follow-up after discontinuation of imatinib. Conclusions: In our population of CP-CML pts treated with imatinib, a majority of patients achieved complete cytogenetic and major molecular responses, with a prolonged of OS and EFS and good safety profile. Sokal score showed better prognosis prediction than Hasford. Early onset of imatinib therapy led to better outcomes and justifies imatinib as front-line treatment of our patients. Disclosures: No relevant conflicts of interest to declare.

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