scholarly journals Results of high-dose imatinib mesylate in intermediate Sokal risk chronic myeloid leukemia patients in early chronic phase: a phase 2 trial of the GIMEMA CML Working Party

Blood ◽  
2009 ◽  
Vol 113 (15) ◽  
pp. 3428-3434 ◽  
Author(s):  
Fausto Castagnetti ◽  
Francesca Palandri ◽  
Marilina Amabile ◽  
Nicoletta Testoni ◽  
Simona Luatti ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Imatinib Mesylate ◽  
Myeloid Leukemia ◽  
Standard Dose ◽  
Prospective Trial ◽  
Chronic Phase ◽  
Working Party ◽  
Response Rates ◽  
High Dose ◽  
Molecular Response

AbstractImatinib mesylate has become the treatment of choice for chronic myeloid leukemia (CML): the standard dose for chronic- phase (CP) CML is 400 mg daily. Response rates are different according to Sokal score, being significantly lower in intermediate and high Sokal risk patients. Phase 1 and 2 trials have shown a dose-response effect and high-dose imatinib trials in early CP CML showed better results compared with standard dose. Our study is the first prospective trial planned to evaluate the efficacy and tolerability of high-dose imatinib in previously untreated intermediate Sokal risk CML patients. Seventy-eight patients were treated with 400 mg imatinib twice daily: complete cytogenetic response (CCgR) rates at 12 and 24 months were 88% and 91%; moreover, at 12 and 24 months 56% and 73% of CCgR patients achieved a major molecular response. The incidence of adverse events was slightly higher than reported by the most important standard-dose trials. With a median follow-up of 24 months, 3 patients progressed to advanced phase. In intermediate Sokal risk newly diagnosed CML patients, high-dose imatinib induced rapid and high response rates, apparently faster than those documented in the International Randomized Study of IFN and Imatinib for the same risk category. These clinical trials are registered at www.clinicaltrials.gov as no. NCT00510926.

scholarly journals Phase III, Randomized, Open-Label Study of Daily Imatinib Mesylate 400 mg Versus 800 mg in Patients With Newly Diagnosed, Previously Untreated Chronic Myeloid Leukemia in Chronic Phase Using Molecular End Points: Tyrosine Kinase Inhibitor Optimization and Selectivity Study

2010 ◽  
Vol 28 (3) ◽  
pp. 424-430 ◽  
Author(s):  
Jorge E. Cortes ◽  
Michele Baccarani ◽  
François Guilhot ◽  
Brian J. Druker ◽  
Susan Branford ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Imatinib Mesylate ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Phase Iii ◽  
High Dose ◽  
Hematologic Toxicity ◽  
Molecular Response ◽  
Newly Diagnosed ◽  
Gastrointestinal Problems

PurposeTo evaluate the safety and efficacy of initial treatment with imatinib mesylate 800 mg/d (400 mg twice daily) versus 400 mg/d in patients with newly diagnosed chronic myeloid leukemia in chronic phase.Patients and MethodsA total of 476 patients were randomly assigned 2:1 to imatinib 800 mg (n = 319) or 400 mg (n = 157) daily. The primary end point was the major molecular response (MMR) rate at 12 months.ResultsAt 12 months, differences in MMR and complete cytogenetic response (CCyR) rates were not statistically significant (MMR, 46% v 40%; P = .2035; CCyR, 70% v 66%; P = .3470). However, MMR occurred faster among patients randomly assigned to imatinib 800 mg/d, who had higher rates of MMR at 3 and 6 months compared with those in the imatinib 400-mg/d arm (P = .0035 by log-rank test). CCyR also occurred faster in the 800-mg/d arm (CCyR at 6 months, 57% v 45%; P = .0146). The most common adverse events were edema, gastrointestinal problems, and rash, and all were more common in patients in the 800-mg/d arm. Grades 3 to 4 hematologic toxicity also occurred more frequently in patients receiving imatinib 800 mg/d.ConclusionMMR rates at 1 year were similar with imatinib 800 mg/d and 400 mg/d, but MMR and CCyR occurred earlier in patients treated with 800 mg/d. Continued follow-up is needed to determine the clinical significance of earlier responses on high-dose imatinib.

scholarly journals Chronic myeloid leukemia: successful therapy with nilotinib in a young patient with high Sokal risk and in sub-optimal response with imatinib

2015 ◽  
Vol 4 (6S) ◽  
pp. 13-16
Author(s):  
Fausto Palmieri
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Young Patient ◽  
Myeloid Leukemia ◽  
Second Generation ◽  
Kinase Inhibitor ◽  
Standard Dose ◽  
Chronic Phase ◽  
Molecular Response ◽  
Optimal Response ◽  
Increased Risk

Here we describe a case of a young patient with chronic myeloid leukemia, at high-risk according to the Sokal index, who started imatinib at standard dose and obtained a sub-optimal response at 12 months. This condition was not automatically an indication to change therapy, but considering the patient as suboptimal, we decided to switch to a second-generation tyrosine kinase inhibitor (TKI), nilotinib 800 mg/die, obtaining soon a complete cytogenetic response (CCYR), thereafter a major molecular response (MMolR). Delayed achievement of cytogenetic and molecular is associated with increased risk of progression among patients with chronic myeloid leukemia in early chronic phase receiving imatinib therapy. Therefore we can hypothesise that this kind of patient could be elegible for an early switch to second-generation TKI.

Mutation Analysis of ABL1 Gene and its Relation to the Achievement of Major Molecular Response in Indonesian Chronic Myeloid Leukemia Patients

2020 ◽  
Vol 17 (1) ◽  
pp. 48-54
Author(s):  
Reni Widyastuti ◽  
Melva Louisa ◽  
Ikhwan Rinaldi ◽  
Riki Nova ◽  
Instiaty Instiaty ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Imatinib Mesylate ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Chronic Phase ◽  
Kinase Domain ◽  
Molecular Response ◽  
Major Molecular Response ◽  
Cross Sectional ◽  
Imatinib Resistance

Background: Imatinib mesylate is the first tyrosine kinase inhibitor approved for chronic myeloid leukemia (CML) therapy. Imatinib is an effective drug. However, previous studies have shown that about 20-30% of patients eventually would develop resistance to imatinib. Approximately 40% of imatinib resistance is associated with BCRABL kinase domain mutation. One of the most common and serious variations account for imatinib response is T315I of ABL1 gene. Objective: The study aimed to examine the association of T315I mutation with the ABL1 gene and its relation to major molecular response (MMR) achievement in CML patients. This study also examined other mutations adjacent to T315I, i.e., F311I, F317L, and different possible variations in the ABL1 gene. Methods: This was a cross-sectional study on Indonesian CML patients in chronic phase. We analyzed 120 blood samples from patients in chronic phase who have received imatinib mesylate (IM) for ≥12 months. Results: There were no T315I, F311I, and F317L mutations found in this study. However, we found another variation, which was 36 substitutions from A to G at position 163816 of ABL1 gene (according to NG_012034.1). Conclusions: We found no T315I, F311I, and F317L mutations in this study. Our findings suggest that there might be other factors that influenced the MMR achievement in our study patients. However, there were 36 substitutions from A to G at position 163.816 (according to NG_012034.1) that needed further examination to explore the significance of this mutation in clinical practice.

Imatinib High Dose (800 mg): Results of a Phase II Trial of the GIMEMA (Gruppo Italiano Malattie Ematologiche Dell’Adulto) CML Working Party in Intermediate Sokal Risk Patients and Status-of-the-Art of an Ongoing Multinational, Prospective Randomized Trial of Imatinib Standard Dose (400 mg Daily) vs High Dose (800 mg Daily) in High Sokal Risk Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4776-4776
Author(s):  
Gianantonio Rosti ◽  
Fausto Castagnetti ◽  
Marilina Amabile ◽  
Nicoletta Testoni ◽  
Angela Poerio ◽  
...  
Keyword(s):  
Phase Ii ◽  
Standard Dose ◽  
Chronic Phase ◽  
Working Party ◽  
Great Majority ◽  
Observation Time ◽  
Phase Iii ◽  
High Dose ◽  
Molecular Response ◽  
Risk Patients

Abstract Imatinib has become the treatment of choice for CML. The standard dose (SD) for CP CML is 400 mg daily: results are less favourable in pts at high or intermediate Sokal risk vs low Sokal risk ones. In intermediate Sokal risk, the IRIS trial (Hughes et al NEJM 349:15, 2003 ) reported at 12 mos a complete cytogenetic response (CCgR- 0% Ph-pos) rate of 67% and a major molecular response (MMolR) rate of 45%. Pre-clinical and clinical data suggest that high doses (HD - 800 mg daily) of ima may be more effective. The GIMEMA CML Working party is conducting a phase II, multi-istitutional prospective study (serial n. CML/021) to investigate the effects of imatinib HD in intermediate Sokal risk. Between Jan, 2004 and May, 2005, 25 centers enrolled 82 pts (80 eval); median age 56 yrs (26–79). Pts evaluable at 3,6 and 12 mos are 80, 77 and 65, respectively. The median observation time is 12 mos. At 3 and 6 mos, 83% and 97% of the pts reached a stable CHR. At 6 mos, 86% obtained a CCgR and 53% of CCgR pts a MMolR (Bcr-Abl/Abl × 100 ratio < 0.1%). At 12 mos, the CCgR rate was 90% and the MMolR rate was 57%. One patient progressed to accelerated/blastic phase. The compliance to HD treatment was good: at 3, 6 and 12 mos 55%, 52% and 52% of the pts received a median daily dose of imatinib > 600 mg. Non hematopoietic AEs accounted for the great majority of dose reductions. The results of this trial further indicate that imatinib HD induces higher and more rapid responses in intermediate Sokal risk CML pts in early chronic phase, being superior to the results obtained with SD (IRIS) and in the range of the MD Anderson results (Kantarjian et al Blood 2004 103:2873). A second project is reserved to high Sokal risk CML pts in early CP: a multinational group, within EuropeanLeukemianet CML WP, is conducting a phase III trial (1:1) of imatinib 400 mg vs 800 mg. By July 31, 2005, 141 patients have been enrolled: GIMEMA (88 pts), Nordic CML Study Group (Sweden, Denmark, Norway and Finland) (25 pts), Turkey (25 pts) and Israel (3 pt).

High and Early Rates of Cytogenetic and Molecular Response with Nilotinib 800 Mg Daily as First Line Treatment of Ph-Positive Chronic Myeloid Leukemia in Chronic Phase: Results of a Phase 2 Trial of the GIMEMA CML Working Party

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 181-181 ◽  
Author(s):  
Gianantonio Rosti ◽  
Fausto Castagnetti ◽  
Angela Poerio ◽  
Massimo Breccia ◽  
Luciano Levato ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Working Party ◽  
Hematologic Toxicity ◽  
Molecular Response ◽  
Average Dose ◽  
Open Label ◽  
Grade Iii

Abstract Imatinib (IM) 400 mg daily is the standard treatment for chronic myeloid leukemia in early chronic phase (ECP): the results of the IRIS trial have shown a 72 months overall survival of 95%; EFS and PFS were 83% and 93%, respectively; the cumulative rate of complete cytogenetic response (CCgR) for the IM 400 mg arm was 25% at 3 months (at 6, 12, 18 and 60 months it was 51%, 69%, 76% and 87%, respectively). Nilotinib, a second generation TKI, has a higher binding affinity and selectivity for Abl with respect to IM, being 20 to 50 times more active in IM-sensitive cell lines and is highly effective in IM resistant patients, across every disease phase. To investigate the therapeutic efficacy and the safety of nilotinib 400 mg BID in untreated, ECP, Ph-pos CML patients, the italian GIMEMA CML Working Party is conducting an open-label, single stage, multicentric, phase II study trial (ClinicalTrials.gov. NCT00481052); all patients provided written informed consent. The primary endpoint is the CCgR rate at 1 year; the kinetic of molecular response is studied by Q-PCR baseline and after 1, 2, 3, 6, 9 and 12 months from treatment start. PATIENTS Seventy-three patients have been enrolled from 20 Centres between June, 2007 and February, 2008. The median age was 51 years (range 18–83), 45% low, 41% intermediate and 14% high Sokal risk. Median follow-up is currently 210 days (range 68–362). RESULTS All 73 patients and 48/73 (66%) completed 3 and 6 months on treatment, respectively. Response at 3 and 6 months (ITT): the CHR rate was 100% and 98%, the CCgR rate 78% and 96%, respectively. A MMR, defined as a BCR-ABL:ABL ratio < 0.1% according to the International Scale, was achieved by 3% of all treated patients after 1 month on treatment, but this proportion rapidly increased to 22% after 2 months, 59% after 3 months and 74% after 6 months. One patient progressed at 6 months to accelerated-blastic phase with the T315I mutation. NILOTINIB DOSE AND COMPLIANCE No dose escalation was permitted in case of resistance; the median daily average dose was close to the intended dose, 789 mg (range 261 – 800); 34/73 patients (47%) interrupted nilotinib at least once, with a median duration of dose interruption of 15 days (range 2–98). The dose of nilotinib at the last visit was 400 mg BID for 52 patients (71%), 400 mg daily for 20 patients (27%) and 200 mg daily for 1 patient (1%). ADVERSE EVENTS: AEs (grade III/IV) were manageable with appropriate dose adaptations: hematologic toxicity was recorded so far in 4 pts (5% - only 1 event grade IV neutropenia); the most frequent biochemical laboratory abnormalities (grade III) were total bilirubin increase (15%), GOT/GPT increase (11%) and lipase increase (4%). Only 1 episode of grade IV lipase increase was recorded. It is noteworthy, considering the 48 cases with at least 6 months of follow-up, that the incidence of any grade II and III nonhematologic adverse event, decreased from 50% and 8% (first 3 months) to 23% and 6% (second trimester), respectively. ECG monitoring: in 16 patients (22%), transient and not clinically relevant ECG abnormalities have been recorded; 2 more patients (3%) revealed a transient and uneventful QTc prolongation (>450 but <499 msec). CONCLUSIONS: The results that have been achieved in these unselected patients and within a multicentric trial, strongly support the notion that in ECP Ph-pos CML patients both cytogenetic and molecular responses to nilotinib are substantially faster than the responses to IM. Acknowledgments: Work supported by European LeukemiaNet, COFIN, University of Bologna and BolognAIL.

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.

ABCB1 Haplotypes Are Associated With Lower P-Gp Activity and Major Molecular Response But Do Not Affect Imatinib Plasma Levels In Chronic Myeloid Leukemia Patients

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3860-3860
Author(s):  
Douglas Vivona ◽  
Luciene Terezina Lima ◽  
Alice C Rodrigues ◽  
Carolina Tosin Bueno ◽  
Cristiane M Gaitani ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Chronic Myeloid Leukemia ◽  
Functional Activity ◽  
Plasma Levels ◽  
Myeloid Leukemia ◽  
Standard Dose ◽  
Chronic Phase ◽  
Molecular Response ◽  
Wild Type ◽  
Major Molecular Response

Abstract Background Despite the high efficacy of IM treatment in chronic myeloid leukemia (CML), some patients fail to achieve optimal response. Several studies demonstrated that IM is a substrate of membrane transporters, such as ABCB1 (P-gp, MDR1) and variations in protein expression or activity could affect the pharmacokinetics of IM by reducing or increasing its bioavailability. These alterations could be related with single nucleotide polymorphisms in ABCB1 gene. Previous data confirms that haplotypes containing the mutated alleles for ABCB1 c.1236C>T, c.3435C>T and c.2677G>T showed major structural modifications that result in changes in the conformation of the binding sites of P-gp. These modifications could affect the pharmacokinetics of IM. Aim The aim of this study was to evaluate the influence of the different haplotypes for ABCB1 c.1236C>T, c.3435C>T and c.2677TG>T polymorphisms in IM plasma concentration, P-gp activity and IM response from CML patients treated with standard dose of IM (400 mg/day). Methods Twenty eight patients in chronic phase of CML were selected according to the haplotypes for ABCB1 c.1236C>T, c.3435C>T and c.2677G>T polymorphisms at two health centers in São Paulo, Brazil. Ten patients with ABCB1 1236CC/3435CC/2677GG haplotype comprised the wild-type group and 18 carriers of haplotypes with at least one mutated allele in each genotype for three ABCB1 polymorphisms (10 patients with 1236CT/3435CT/2677GT and 8 with 1236TT/3435TT/2677TT) comprised the mutated group. Patients were matched for IM time of use. All patients were in chronic phase of CML, treated with a standard dose of IM (400 mg/day) for a median time of 63.5±12.6 months and with complete cytogenetic response (CCyR). Major molecular response (MMR) was defined as a reduction of BCR-ABL1 transcripts levels to ≤ 0.1% in the peripheral blood standardized on the International scale. Complete molecular response (CMR) was defined as a reduction ≤0.0032% of BCR-ABL1 transcripts levels. Real-Time PCR was performed to evaluate ABCB1 mRNA expression to control gene GAPDH. P-gp functional activity was determinated by rhodamine123 efflux assay. Analysis of P-gp expression and functional activity were performed by flow cytometry. The determination of plasma concentration of IM was performed by capillary electrophoresis. Results Patients without MMR had lower plasma concentration of IM when compared to those that achieved this response (0.51 µg/mL vs. 1.42 µg/mL, P=0.001) but no association was found between the different haplotypes and IM plasma levels or ABCB1 mRNA/P-gp expression. The median of Rh123 efflux in wild-type and mutated groups was 59.1 (54.8 - 69.5) and 38.3 (27.4 - 47.9) (P<0.05), respectively. Patients who did not achieve MMR showed a higher rate of efflux mediated by P-gp compared to individuals who did not achieve this response (64.7% vs. 45.7%, P =0.001). All patients who did not achieve MMR showed efflux above 60%.There was a strong and positive correlation between ABCB1 mRNA expression and P-gp expression (r=0.747, P=0.001). P-gp activity was positive and moderate correlated with BCR-ABL1 transcripts (r=0.570; P=0.001). Conclusion ABCB1 1236CT/3435CT/2677GT and 1236TT/3435TT/2677TT haplotypes are associated with lower P-gp activity and higher frequency of MMR but not with IM plasma concentration in chronic phase CML patients treated with standard-dose of IM (400 mg/day) Disclosures: No relevant conflicts of interest to declare.

Comparison of imatinib 400 mg and 800 mg daily in the front-line treatment of high-risk, Philadelphia-positive chronic myeloid leukemia: a European LeukemiaNet Study

Blood ◽  
2009 ◽  
Vol 113 (19) ◽  
pp. 4497-4504 ◽  
Author(s):  
Michele Baccarani ◽  
Gianantonio Rosti ◽  
Fausto Castagnetti ◽  
Ibrahim Haznedaroglu ◽  
Kimmo Porkka ◽  
...  
Keyword(s):  
High Risk ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Standard Treatment ◽  
Response Rate ◽  
Standard Dose ◽  
High Dose ◽  
Molecular Response ◽  
Front Line ◽  
To Receive

AbstractImatinib mesylate (IM), 400 mg daily, is the standard treatment of Philadelphia-positive (Ph+) chronic myeloid leukemia (CML). Preclinical data and results of single-arm studies raised the suggestion that better results could be achieved with a higher dose. To investigate whether the systematic use of a higher dose of IM could lead to better results, 216 patients with Ph+ CML at high risk (HR) according to the Sokal index were randomly assigned to receive IM 800 mg or 400 mg daily, as front-line therapy, for at least 1 year. The CCgR rate at 1 year was 64% and 58% for the high-dose arm and for the standard-dose arm, respectively (P = .435). No differences were detectable in the CgR at 3 and 6 months, in the molecular response rate at any time, as well as in the rate of other events. Twenty-four (94%) of 25 patients who could tolerate the full 800-mg dose achieved a CCgR, and only 4 (23%) of 17 patients who could tolerate less than 350 mg achieved a CCgR. This study does not support the extensive use of high-dose IM (800 mg daily) front-line in all CML HR patients. This trial was registered at www.clinicaltrials.gov as #NCT00514488.

scholarly journals The Comparison of Dasatinib 70 Mg/Day to 100 Mg/Day in Newly Diagnosed Patients with Chronic Myeloid Leukemia in Chronic Phase (CML-CP): A Multicenter, Prospective, Randomized Controlled Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3615-3615
Author(s):  
Dan Yu ◽  
Zhuangzhi Yang ◽  
Hui Cheng ◽  
Rui Jiang ◽  
Jingming Guo ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Standard Dose ◽  
Chronic Phase ◽  
Controlled Study ◽  
Molecular Response ◽  
Newly Diagnosed ◽  
Efficacy And Safety ◽  
Best Response ◽  
Significant Difference

Abstract Background: The purpose of this study is to compare efficacy and safety of patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) treated with frontline dasatinib 70 mg/day with those who received standard-dose dasatinib 100 mg/day. Method: From July 2019 to July 2021, 81 patients with newly diagnosed CML-CP were enrolled across 11 centers. All of the patients were randomly treated with dasatinib 70 mg/day (N=43) or standard-dose dasatinib 100 mg/day (N=38). Results: Among 81 enrolled patients, 16 patients were off study at different times for different reasons.All patients achieved hematological remission after 3 months of treatment, and the best response rates were 84.00% (21/25) and 88.89% (24/27) for 70mg/d and 100mg/d groups (P&gt;0.05).At 6 months, the best response, complete cytogenetic response (CCyR) and major molecular response (MMR) rate were 94.44% vs 92.86% (P &gt; 0.05), 94.44% vs 92.86% (P &gt; 0.05) and 55.56% vs 71.43% (P &gt; 0.05), respectively.At 9 months, the rates of CCyR and MMR were 90.91% vs 88.89% (P &gt; 0.05) and 66.67% vs 72.73% (P &gt; 0.05);CCyR and MMR by 12 months, respectively, were 90.91% vs 100.00% (P &gt; 0.05), 81.82% vs 80.00% (P &gt; 0.05).The adverse events (AEs) of the two groups were mild, and there was no significant difference (P &gt; 0.05).The most common grade ≥3 hematological AEs in 70 mg/d group were leukopenia (1/43), neutropenia (1/43) and anemia (2/43), and In 100mg/d group were leukopenia (4/38), neutropenia (6/38), anemia (3/38) and thrombocytopenia (3/38). Conclusions: Our study suggests that patients with newly diagnosed CML-CP treated with dasatinib 70 mg/day or 100 mg/day, there is no significant difference in efficacy and safety. Decreasing the dose of dasatinib can ensure the efficacy of patients, while reducing the economic burden of patients and increasing patient compliance. Disclosures No relevant conflicts of interest to declare.

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