Imatinib Mesylate Induces High Complete Cytogenetic and Molecular Response Rates in Children and Adolescents with Philadelphia Chromosome-Positive (Ph+) Chronic Myelogenous Leukemia (CML) in Chronic Phase (CP)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4273-4273
Author(s):  
Fiorina Giona ◽  
Maria Caterina Putti ◽  
Maria Luisa Moleti ◽  
Mauro Nanni ◽  
Anna Maria Testi ◽  
...  
Keyword(s):  
Children And Adolescents ◽  
Imatinib Mesylate ◽  
Kinase Inhibitor ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Myelogenous Leukemia ◽  
Molecular Response ◽  
Real Time Quantitative Pcr

Abstract Imatinib mesylate (IM), a BCR-ABL tyrosine kinase inhibitor, is an effective therapy for CML in adults and has shown efficacy in children with Ph+ leukemias. The aim of this study was to evaluate the efficacy of IM in Ph+ CML patients (pts) in CP aged <18 years at diagnosis, previously untreated or resistant to Interferon (IFN). In all pts, IM therapy, started at a dose of 340 mg/m2/day, was modulated according to the hematologic parameters. Cytogenetic studies were performed on bone marrow (BM) cells at baseline and, during IM therapy, every 3 months (mo). Complete cytogenetic response (CCyR) was also confirmed by FISH. BCR-ABL transcripts were measured in the peripheral blood (PB) cells every mo and in the BM cells every 3 mo by real-time quantitative PCR (RQ-PCR). Molecular response (MolR) was defined as major in the presence of a BCRABL: ABL ratio <0.05% and as complete with a ratio <0.001. Between February 2001 and October 2007, 13 Ph+ CML pts (9 M and 4 F; median age 128/12 years) in CP were recruited from 2 pediatric centers (Rome and Padua). Eight of the 13 pts (7 M and 1 F; median age 11 years) received IM at diagnosis and 5 (3 F and 1 M; median age 146/12 years) after IFN therapy given at a mean dose of 6.000.000 UI/day for a median of 18 mo. All but 1 pt tolerated well IM treatment. The mean dose of IM administered was 326 mg/m2/day for untreated pts and 227 mg/m2/day for those resistant to IFN. The characteristics and followup of the pts are summarized in the Table: Sex/Age at diagn/Age at treat (yrs) IFN duration/%Ph+ IM mg/m2/day CCyR/time (mo) Max Bcr-Abl:Abl (%)/time (mo) (BM) Max Bcr-Abl:Abl (%)/time (mo) (PB) CCyR duration (mo) Follow-up .F/11/146/12 40 mo/100 193.5 4 0/60 0/4 +80 Alive CCyR, Bcr-Abl:Abl (%)BM 0 PB 0.0023 F/179/12/1810/12 9 mo/100 182 6 1.27/9 0.89/9 +7 Lost to follow-up in CCyR at + 13 mo M/91/12/117/12 26 mo/50 208 3 0/36 0/12 +65 Alive CCyR, Bcr-Abl:Abl (%)BM 0 PB 0 F/89/12/910/12 13 mo/50 350 3 0/44 0/66 +66 Alive CCyR, Bcr-Abl:Abl (%)BM 0.009 PB 0 M/172/12/189/12 18 mo/80 205 9 0.029/68 0.114/72 +82 Alive CCyR, Bcr-Abl:Abl (%)BM 0.05 PB 0.15 M/126/12 −/100 310 4 0/42 0/30 +66 Alive CCyR, Bcr-Abl:Abl (%): BM 0 PB 0 M/161/12 −/100 327 n.e. n.e. n.e. n.e. IM tox; alive CCyR after SCT (sibl) (+40 mo) M/144/12 −/100 291 4 0/42 0/24 +61 Alive CCyR, Bcr-Abl:Abl (%) BM 0 PB 0 M/811/12 −/100 357.5 6 0.044/9 0.057/9 CyRel/33 Alive CCyR after SCT (+ 8 mo) M/95/12 −/100 326 3 0.013/12 0.028/9 +12 Alive CCyR,Bcr-Abl:Abl (%) BM 0.013 PB 0.15 M/410/12 −/100 328.5 3 0.02/9 0/12 BMT/+13 SCT (sibl) in CCyR->Alive in CCyR +43 mo M/137/12 −/100 349 6 0.012/30 0.025/30 +32 Alive CCyR, Bcr-Abl:Abl (%) BM 0.012 PB 0.025 F/94/12 −/100 320 3 0.009/9 0.003/9 +7 Alive CCyR, Bcr-Abl:Abl (%) BM 0.02 PB 0.003 Twelve of the 13 pts (92%) achieved a CCyR after a median of 4 mo (range 3–9). Eleven of the latter 12 pts were evaluated for MolR: 11/11 (100%) pts achieved a MolR, 6 major (54.5%) and 5 complete (45.5%), on BM cells after a median of 36 mo (range 9–68) and 9/11 pts (82%) on PB cells, 4 major (44.4%) and 5 complete (55.6%), after a median of 12 mo (range 4–66). To date, 12 evaluable pts are alive in CCyR: 3 after a stem cell transplantation (SCT) and 9 still receiving IM for a median time of 68 mo (range 10–89). MolR persists on BM cells in 9/9 pts (100%), 4 complete (44%), and on PB cells in 7/9 pts (78%), 4 complete. Our experience indicates that IM is highly effective in children and adolescents with Ph+ CML in CP, capable also of inducing high and persistent CCyR and MolR rates also in pts resistant to IFN.

High-dose imatinib mesylate therapy in newly diagnosed Philadelphia chromosome–positive chronic phase chronic myeloid leukemia

Blood ◽  
2004 ◽  
Vol 103 (8) ◽  
pp. 2873-2878 ◽  
Author(s):  
Hagop Kantarjian ◽  
Moshe Talpaz ◽  
Susan O'Brien ◽  
Guillermo Garcia-Manero ◽  
Srdan Verstovsek ◽  
...  
Keyword(s):  
Imatinib Mesylate ◽  
Quantitative Polymerase Chain Reaction ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Myelogenous Leukemia ◽  
High Dose ◽  
Molecular Response ◽  
Newly Diagnosed ◽  
Complete Cytogenetic Response

Abstract Imatinib mesylate (STI571) is effective in chronic phase chronic myelogenous leukemia (CML). However, most patients treated with 400 mg imatinib daily have variable levels of residual molecular disease. We treated 114 patients with newly diagnosed chronic phase CML with 400 mg imatinib twice daily. Overall, 109 patients (96%) had a major cytogenetic response (Philadelphia chromosome [Ph] < 35%), and 103 (90%) had a complete response (Ph 0%). With a median follow-up of 15 months, no patient has progressed to accelerated or blastic phase. The estimated 2-year survival rate was 94%. By quantitative polymerase chain reaction (QPCR) studies, 71 (63%) of 112 patients showed BCR-ABL/ABL percentage ratios decrease to less than 0.05%, and 31 (28%) to undetectable levels. Compared with standard-dose imatinib, high-dose imatinib was associated with significantly better complete cytogenetic response (P = .0005), major molecular response (QPRC < 0.05%; P = .00001), and complete molecular response (undetectable BCR-ABL; P = .001). High-dose imatinib was well tolerated but resulted in more frequent myelosuppression; 82% of patients continue to receive 600 mg or more of imatinib daily. In conclusion, high-dose imatinib induced higher rates of complete cytogenetic response and of molecular response in patients with newly diagnosed chronic phase CML. (Blood. 2004; 103:2873-2878)

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.

scholarly journals Nilotinib therapy in an imatinib intolerant chronic myeloid leukemia patient with pulmonary severe hypertension

2015 ◽  
Vol 4 (2S) ◽  
pp. 17-20
Author(s):  
Mario Annunziata
Keyword(s):  
Side Effects ◽  
Tyrosine Kinase ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Chronic Phase ◽  
Chronic Myeloid Leukemia Patient ◽  
Cytogenetic Response ◽  
Myelogenous Leukemia ◽  
Molecular Response ◽  
Cutaneous Rash

Imatinib mesylate is a tyrosine kinase inhibitor that has significant efficacy in the treatment of chronic myelogenous leukemia. In general, hematologic and extrahematologic side effects of imatinib therapy are mild to moderate, with the large majority of patients tolerating prolonged periods of therapy. However, a minority of patients are completely intolerant of therapy, while others are able to remain on therapy despite significant side effects. Here, we describe a chronic phase CML patient with pulmonary arterial hypertension, mechanical hearth valve, who experienced extrahematologic adverse event (persistent grade III cutaneous rash, despite two discontinuations of imatinib and using of steroid). Necessitating switch to one of new tyrosine kinase inhibitors, nilotinib, has resulted in complete cytogenetic response and major molecular response, after 3 and 6 months, respectively. No cross-intolerance with imatinib was observed during nilotinib therapy. Besides, this clinical case suggests that warfarin and nilotinib can be used concurrently without the risk of increased anticoagulant effect.

Clinical Outcome of CML Patients with Philadelphia Chromosome Complex Variants.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4499-4499
Author(s):  
Santiago del Castillo ◽  
Regina Garcia Delgado ◽  
Laura Entrena ◽  
Agustin M Hernandez ◽  
Arturo Campos ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Philadelphia Chromosome ◽  
Genetic Material ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Molecular Response ◽  
Imatinib Treatment ◽  
Current State ◽  
Worse Prognosis

Abstract Abstract 4499 INTRODUCTION: The presence of translocation between chromosomes 9 and 22 that characterizes the chronic myeloid leukemia (CML) is occasionally accompanied by more complex variations involving additional exchange of genetic material with other chromosomes. This variants of Philadelphia chromosome have no worse prognosis than those others with the common translocation. MATERIAL: Since 1997 we have diagnosed in our hospital 5 CML patients who didn't show any of these variants. Three women 17, 23 and 76 years old and two men of 36 and 65. All of them diagnosed in chronic phase. Risk stage at diagnosis by Sokal were 1 high, 1 intermediate and 3 low. By Hasford 2 were intermediate end 3 low. Philadelphia chromosome variants involve a third chromosome in 4 cases (translocations 2;9;22, 9;22;12, 9;22;9 and 6;9;22) and in one case involving four chromosomes (translocation 1;2;9;22). Three patients diagnosed before the imatinib approval started treatment with IFN and Ara-C and subsequently changed to Imatinib treatment. Two others started treatment with imatinib directly. RESULTS: All patients had a good outcome with treatment being the current state of 2 patients in complete molecular response (105 and 60 months of follow-up) and 2 patients in Major Molecular Response (146 and 143 months). The 5th patient, a 17 years old woman, has been treated for three months with Imatinib and showed complete haematological response at first month and major cytogenetic response at third month. It is striking in this last patient the fact that two years earlier had been referred for study of myeloid moderate leukocytosis (20,000 leukocytes with circulating myeloid progenitors without anemia, thrombocytosis, or splenomegaly). The patient didn't come to clinic when Bone Marrow Test was cited and two years later resumes the visit continuing with the same leukocytosis in peripheral blood and without splenomegaly unchanged despite not having received any treatment. CONCLUSION: Our experience confirm that this type of patients with complex translocation variants have no worse prognosis than normal translocation under imatinib treatment and suggests that may have a more benign clinical behavior. Disclosures: No relevant conflicts of interest to declare.

Imatinib mesylate therapy in newly diagnosed patients with Philadelphia chromosome–positive chronic myelogenous leukemia: high incidence of early complete and major cytogenetic responses

Blood ◽  
2003 ◽  
Vol 101 (1) ◽  
pp. 97-100 ◽  
Author(s):  
Hagop M. Kantarjian ◽  
Jorge E. Cortes ◽  
Susan O'Brien ◽  
Francis Giles ◽  
Guillermo Garcia-Manero ◽  
...  
Keyword(s):  
Imatinib Mesylate ◽  
Chronic Myelogenous Leukemia ◽  
Quantitative Polymerase Chain Reaction ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Myelogenous Leukemia ◽  
Interferon Α ◽  
Combination Regimens ◽  
Philadelphia Chromosome Positive

Abstract Fifty patients with Philadelphia chromosome–positive (Ph+) chronic myelogenous leukemia (CML) in early chronic phase received imatinib mesylate, 400 mg orally daily. After a median follow-up of 9 months, 49 patients (98%) achieved a complete hematologic response and 45 patients (90%) achieved a major cytogenetic response, complete in 36 patients (72%). Compared with similar patients who received interferon-α with or without hydroxyurea or other interferon-α combination regimens, those receiving imatinib mesylate had higher incidences of complete and major (Ph &lt; 35%) cytogenetic responses at 3 months (34% and 74% versus 1%-4% and 9%-24%, respectively), 6 months (52% and 80% versus 3%-7% and 11%-28%, respectively), and 9 months (60% and 77% versus 5%-11% and 14%-30%, respectively; P &lt; .001). Competitive quantitative polymerase chain reaction (QPCR) studies at 9 months showed a median QPCR value (ratio of BCR-ABL/ABL transcripts × 100) of 0.59% overall and of 0.24% (range, 0.001%-29.5%) for complete cytogenetic response.

Dasatinib (SPRYCEL®) in Patients (pts) with Chronic Myelogenous Leukemia in Accelerated Phase (AP-CML) That Is Imatinib-Resistant (im-r) or -Intolerant (im-i): Updated Results of the CA180–005 ’START-A’ Phase II Study.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2160-2160 ◽  
Author(s):  
Jorge Cortes ◽  
D.W. Kim ◽  
F. Guilhot ◽  
G. Rosti ◽  
R.T. Silver ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Mutational Analysis ◽  
Present Report ◽  
Cytogenetic Response ◽  
Myelogenous Leukemia ◽  
Molecular Response ◽  
Significant Activity ◽  
Hematologic Response ◽  
Grade 3

Abstract Dasatinib (SPRYCEL®, formerly BMS-354825) is a novel, oral, multi-targeted kinase inhibitor that induces complete hematologic and cytogenetic remissions in pts in all phases of im-r or im-i CML. START-A is an open-label study of dasatinib in pts with im-r or im-i AP-CML. Preliminary results with early follow-up suggested significant activity. The present report updates the results of this study with a minimum of 9 months of follow-up. Dasatinib was given orally at 70 mg twice daily (BID). Dose escalation to 100 mg BID was allowed for inadequate initial response and reduction to 50 or 40 mg BID for persistent toxicity. Evaluation included weekly blood counts and monthly bone marrow including cytogenetics. Molecular evaluation of BCR-ABL transcript levels by real-time qPCR was performed at baseline and upon documentation of complete cytogenetic response. A total of 174 pts (161 im-r and 13 im-i) were enrolled between December 2004 and July 2005 in 39 centers worldwide. There were 96 (55%) males; median age was 57 years (range 22–86); median time from original diagnosis of CML was 82 months. Prior therapy included im in all pts (>600 mg/day in 91 (52%), im for >3 years in 103 (59%) pts, interferon in 126 (72%) pts, stem cell transplantation in 23 (13%) pts. Major cytogenetic response (MCyR) to prior im had been seen in 57 (33%) pts. The average daily dose (median across all pts) was 130 mg/day (range 44–199). Major hematologic response (MaHR) was documented in 110 (63%) pts with complete hematologic response in 75 (43%) and no evidence of leukemia in 35 (20%). At 9 months, 85% of pts have maintained their MaHR. MCyR was documented in 65 (37%) pts, complete in 49 (28%), partial in 16 (9%). Median progression-free survival (PFS) has not been reached; estimated PFS at 9 months is 70%. In the 94 pts with BCR-ABL mutations at baseline the MaHR rate was 69%. Generally, response rates were similar in the im-i and im-r groups. Cytopenias were significant with grade 3–4 thrombocytopenia and neutropenia in 82% and 76% of pts, respectively. Non-hematologic toxicities were generally mild to moderate. The most frequent (% any grade, % grade 3–4) were diarrhea (51%, 8%), headache (29%, 1%), fatigue (26%, 4%), fever (25%, 3%) and pleural effusion (25%, 3%). Pleural effusions were optimally managed with dose interruption and diuretics and/or pulse steroids. Dasatinib is highly effective in pts with im-r or im-i AP-CML with high rates of durable MaHR and MCyR. An updated analysis with at least 12 months of follow-up, including molecular response data and mutational analysis at time of progression, will be presented.

Imatinib Mesylate Discontinuation in Patients with Chronic Myelogenous Leukemia in Complete Molecular Remission: An Update Follow Up.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2154-2154 ◽  
Author(s):  
Francois-Xavier Mahon ◽  
Francoise Huguet ◽  
Gabriel Etienne ◽  
Delphine Réa ◽  
Jean-Michel Cayuela ◽  
...  
Keyword(s):  
Imatinib Mesylate ◽  
Chronic Myelogenous Leukemia ◽  
Kinase Inhibitor ◽  
Residual Disease ◽  
Quantitative Polymerase Chain Reaction ◽  
Leukemic Cell ◽  
Myelogenous Leukemia ◽  
Molecular Response ◽  
Molecular Remission

Abstract The BCR-ABL tyrosine kinase inhibitor imatinib mesylate (Gleevec) induces complete cytogenetic responses (CCR) in more than 85% of patients with chronic myelogenous leukemia (CML). However, patients in CCR relapse after imatinib interruption in case of detectable residual disease. In fact, less than 10% of patients achieve a molecular remission, defined by an undetectable residual disease using real time quantitative polymerase chain reaction (RTQ-PCR). We previously reported the outcome of CML patients in CCR after cessation of interferon-alpha during the pre-imatinib era. Seven (all with a negative PCR) out of 15 patients did not relapse (J Clin. Oncol.,20,2002:214–220). In the present study, we address the issue of the discontinuation of imatinib in CML with undetectable residual disease for more than 2 years in 15 patients. The median duration of RTQ-PCR negativity and imatinib therapy were respectively 32 months (24–46) and 45 months (32–56) before imatinib interruption. Eight patients displayed a molecular relapse with a detectable BCR-ABL transcript appearance between the first 6 months. Imatinib was then re-introduced and led to a novel molecular response in most patients. Seven other patients have still an undetectable level of BCR-ABL transcript after a median follow up of 20 months (9–24). With the assumption that the doubling time of a proliferative CML cell is 8 days, it will take a maximum of 6 months if only one leukemic cell persists and proliferates to reach 107 cells i.e corresponding to a residual disease detectable by RTQ-PCR. Relapses observed within 6 months may reflect the kinetic of undetectable dividing CML cells. Those cells may be eradicated or controlled in long term non relapsing patients described in our study.

Patients with Chronic Phase CML in the IRIS Study Who Receive Imatinib Mesylate (IM) 2nd Line after Prior IFN/Ara-C Have Sustained Complete Cytogenetic and Major Molecular Response Rates Similar to 1st Line IM Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2139-2139
Author(s):  
Jaspal Kaeda ◽  
Andreas Hochhaus ◽  
Jerald Radich ◽  
Susan Branford ◽  
Charlene So ◽  
...  
Keyword(s):  
Chronic Phase ◽  
Response Rates ◽  
Cytogenetic Response ◽  
Progression Rate ◽  
Molecular Response ◽  
Major Molecular Response ◽  
Real Time Quantitative Pcr ◽  
Log Reduction ◽  
Advanced Phase

Abstract The IRIS study compared IM and interferon+cytarabine (IFN/Ara-C) in patients (pts) with newly diagnosed CML-CP (n=553 per arm). IFN/Ara-C pts. could cross over to IM if they satisfied predetermined criteria for disease, either resistance/refractoriness (=resistance), or intolerance of or reluctance to continue the combination (=lack of resistance). Pts who received IM 1st line or 2nd line who achieved a complete cytogenetic response (CCyR) had BCR-ABL transcript levels measured serially by real-time quantitative PCR (RQ-PCR). Results were expressed as log reduction in BCR-ABL/BCR from a standardized baseline value for untreated pts. Yearly rates of 3 log reduction (Major Molecular Response, MMR) from IM treatment starting date were estimated by multiplying the CCyR rate by the MMR rate in CCyR pts at each time point. Overall, of 553 pts who received 1st line IM 82% achieved CCyR, an estimated 69% during the 1st year (yr) of treatment. Of 359 pts who received 2nd line IM, 80% achieved CCyR, 62% during the 1st yr; rates were lower in pts with resistance than in those without resistance to prior IFN/Ara-C (75% vs 85% overall, p=0.025, 56% vs 68% within first yr, p<0.01). Best observed and estimated molecular responses for CCyR pts. are summarized in the table. The median follow-up for BCR-ABL evaluation on 1st line vs 2nd line IM was 45 and 35 months, respectively. Molecular response on 1st- and 2nd-line IM in the IRIS study 1st-line IM 2nd-line IM after IFN/Ara-C All pts N = 553 All pts N = 359 Resistance N =174 Lack of resistance N =185 CcyR 454 (82%) 288 (80%) 131 (75%) 157 (85%) Pts with CCyR during treatment and PCR sample(s) N = 401 N = 211 N = 98 N = 113 –≥3 log reduction (MMR) 323 (81%) 154 (73%) 63 (64%) 91 (81%) –≥ 4 log reduction 216 (54%) 92 (44%) 35 (36%) 57 (50%) Estimated % of all pts who achieve CCyR and MMR by – 1 yr 36 24 19 28 – 2 yr 59 38 29 45 – 4 yr 67 67 58 72 – 5 yr 85 82 78 84 Overall response rates were similar between 1st and 2nd line IM pts, although responses in 2nd line IM pts may have occurred more slowly. However, the number of RQ-PCR samples between 1 and 2 yrs of 2nd line IM was limited as samples were not obtained routinely between Jan 2003 and Aug 2004. In pts who achieved CCyR, the estimated 5-yr progression rate to advanced CML phase was 3% for 1st line IM and 4% for 2nd line IM; using the broader definition of progression (including events such as CML-unrelated deaths and loss of MCyR/CHR) the progression rates were 9% and 8% respectively. In both 1st and 2nd line IM pts with CCyR who also achieved MMR, only an estimated 1% progressed to advanced phase within 5 yrs; the estimated broadly defined event rates were 5% and 4% respectively. In summary, for 1st line IM patients with a RQ-PCR follow-up of up to 5 yrs, an estimated 85% achieved MMR at 5 yrs compared with 59% at 2 yrs. Cytogenetic and molecular response rates were similar for 1st line and 2nd line IM pts, primarily due to responses in pts who crossed over for reasons other than resistance or refractoriness. For IM pts the rate of progression to advanced CML phase at 5 yrs was low in those with CCyR and even lower in pts who also achieved MMR.

scholarly journals Initial treatment for patients with CML

Hematology ◽  
2009 ◽  
Vol 2009 (1) ◽  
pp. 453-460 ◽  
Author(s):  
John M. Goldman
Keyword(s):  
Initial Treatment ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Molecular Response ◽  
Major Molecular Response ◽  
Log Reduction ◽  
Advanced Phase

AbstractFor adult patients who present with chronic myeloid leukemia (CML) in chronic phase it is now generally agreed that initial treatment should start with the tyrosine kinase inhibitor (TKI) imatinib at 400 mg daily. Five years after starting imatinib about 60% of these patients will be in complete cytogenetic response (CCyR), still taking imatinib; an appreciable proportion of these will have achieved a major molecular response, defined as a 3-log reduction in the level of BCR-ABL1 transcripts in their blood. The patients in CCyR seem to have a very low risk of relapse to chronic phase or of progression to advanced phase. Other patients may be resistant to imatinib or may experience significant side effects that require change of therapy. The best method of monitoring responding patients is to enumerate Philadelphia chromosome–positive marrow metaphases at 3-month intervals until CCyR and to perform RQ-PCR for BCR-ABL1 transcripts at 3-month intervals after starting imatinib. The recommendations for defining “failure” and “sub-optimal response” proposed by the European LeukemiaNet in 2006 have proved to be a major contribution to assessing responses in individual patients and are now being updated. Patients who fail imatinib may respond to second-generation TKIs, but allogeneic stem cell transplantation still plays an important role for eligible patients who fare badly with TKIs. Patients who present in advanced phases of CML should be treated initially with TKI alone or with TKI in conjunction with cytotoxic drugs, but their overall prognosis is likely to be much inferior to that of those presenting in early chronic phase.

Imatinib mesylate therapy may overcome the poor prognostic significance of deletions of derivative chromosome 9 in patients with chronic myelogenous leukemia

Blood ◽  
2005 ◽  
Vol 105 (6) ◽  
pp. 2281-2286 ◽  
Author(s):  
Alfonso Quintas-Cardama ◽  
Hagop Kantarjian ◽  
Moshe Talpaz ◽  
Susan O'Brien ◽  
Guillermo Garcia-Manero ◽  
...  
Keyword(s):  
Imatinib Mesylate ◽  
Prognostic Significance ◽  
Chronic Phase ◽  
Response Duration ◽  
Cytogenetic Response ◽  
Chromosome 9 ◽  
Myelogenous Leukemia ◽  
Derivative Chromosome

AbstractDeletions of derivative chromosome 9 [der(9)] can be identified by fluorescence in situ hybridization (FISH) in 10% to 15% of patients with chronic myeloid leukemia (CML). Patients with der(9) deletions have been reported to have an adverse outcome when treated with chemotherapy, interferon, and possibly imatinib mesylate. We investigated the frequency and prognostic significance of der(9) deletions among 352 patients with CML treated with imatinib mesylate at our institution, in whom a deletion status of der(9) was determined. Thirty-three patients (9%; 95% CI 0.07, 0.13) (30 in chronic phase, 3 in accelerated phase) had der(9) deletions. The rates of major (82% vs 79%, P = 0.82) and complete cytogenetic response (76% vs 66%, P = .33) with imatinib mesylate therapy were similar in patients with and without der(9) deletions, respectively. After a median follow-up of 28 months, there was no difference in overall survival (P = .30) or response duration (P = .49) in patients with and without deletions. In a multivariate analysis, der(9) deletions had no significant impact on response, survival, or response duration. We conclude that treatment with imatinib mesylate overcomes the adverse prognostic significance of der(9) deletions in patients with CML.

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