Major Molecular Response Rates Research Articles

Long-Term Outcomes in Patients with Chronic Myeloid Leukemia in Chronic Phase Receiving Frontline Nilotinib Versus Imatinib: Enestnd 10-Year Analysis

Long-Term Outcomes in Patients with Chronic Myeloid Leukemia in Chronic Phase Receiving Frontline Nilotinib Versus Imatinib: Enestnd 10-Year Analysis

Efficacy and Safety of Generic Imatinib in Chronic Phase of Chronic Myeloid Leukemia (CP-CML): Experience from a Multi-Center in China

Background: Imatinib is the first TKI that was officially approved by the Food and Drug Administration (FDA) for the treatment of patients (pts) with CP-CML and it is the most commonly used treatment in CML pts on the international scene. Generic imatinib was offered and accessible as frontline treatment of CML in china in June 2013, which predictably lowered the cost of CML therapy. However the statistics regarding their effectiveness and tolerability in greater proportion of the population of CML pts are not available. (ClinicalTrials. gov number, NCT02317159.) Aim: To evaluate the efficacy and safety of generic imatinib in the treatment of pts that were newly diagnosed with CP-CML. Methods: In this multi-center, prospective open-label study, 75 pts with CP-CML were enrolled to receive generic imatinib mesylate capsules at a dose of 400 mg once daily. The primary end point was major molecular response (MMR) by 12 months. Imatinib plasma level and adverse events (AEs) were assessed. Results: The Median age at diagnosis was 46 years (range 19-75 years), and 50 pts (66.7%) were male. The median follow-up was 22.1 (range0.5-24) months. 35 pts (44%), 26 pts (34.7%) and 12 pts (16%) were in low, intermediate and high risk group, respectively, according to Sokal prognostic score (Not available in 2 pts). By 12 months, the cumulative rate of MMR (BCR-ABL1IS ≤0.1%) was 42.7% (32/75), and the cumulative rate of complete cytogenic response (CCyR) was74.7% (56/75). Complete hematologic response (CHR), CCyR, MMR rate at 3 months,6 months and 12 months were shown in Table 1. For pts who presented with BCR-ABL1 IS≤ 10% at 3 months, had better response as compared with those with BCR/ABL1IS> 10% (Table 2). The estimated progression-free survival at 12 months was 94.7%. Imatinib plasma levels at 29 days on imatinib were variable in individual, with 1522.9±775.3 ng/mL for median level (rang 394.4 to3891 ng/mL). Although those numerical values showed difference, no statistically significant correlations were found between imatinib plasma level and CCyR or MMR(P=0.902;P=0.349). The incidents and profile of AEs were similar to those reported previously. Conclusion: This study confirmed that generic imatinib produced in China is effective and well-tolerated in Chinese CP-CML pts. The outcome of generic imatinib in the treatment of CP-CML is similar to brand imatinib reported in the literatures. The introduction of generic imatinib at a reduced and affordable cost may strikingly impact the cost of care for CML and improve the clinical outcomes of CML in China. Disclosures No relevant conflicts of interest to declare.

Efficacy of Bosutinib in Imatinib-Resistant Vs Dasatinib/Nilotinib-Resistant Chronic Phase Chronic Myeloid Leukemia: Results from the Phase 4 BYOND Study

Efficacy of Bosutinib in Imatinib-Resistant Vs Dasatinib/Nilotinib-Resistant Chronic Phase Chronic Myeloid Leukemia: Results from the Phase 4 BYOND Study

Outcome of Patients (Pts) with Philadelphia Chromosome-Positive (Ph+) Acute Lymphoblastic Leukemia (ALL) without 3-Month Complete Molecular Response (CMR)

Outcome of Patients (Pts) with Philadelphia Chromosome-Positive (Ph+) Acute Lymphoblastic Leukemia (ALL) without 3-Month Complete Molecular Response (CMR)

Association of High Body Mass Index with Response Outcomes in Patients with CML-CP Treated with Dasatinib Versus Imatinib in the First Line: Exploratory Post Hoc Analysis of the Phase 3 DASISION Trial

Association of High Body Mass Index with Response Outcomes in Patients with CML-CP Treated with Dasatinib Versus Imatinib in the First Line: Exploratory Post Hoc Analysis of the Phase 3 DASISION Trial

The influence of additive clonal chromosome abnormalities in Ph negative cells on the efficacy of chronic myeloid leukemia

Objective: To investigate the influence of additional clonal chromosome abnormalities in Ph negative cells (CCA/Ph(-)) on the efficacy of chronic myeloid leukemia (CML) after tyrosine kinase inhibitors (TKI) treatment. Methods: The clinical data of 28 CML patients with CCA/Ph(-) treated in Henan Cancer Hospital from July 2014 to December 2017 were analyzed retrospectively. The univariate analysis was carried out by Kaplan-Meier method. Multivariate analysis was done by Cox proportional risk model. Results: A total of 28 CCA/Ph(-)patients were recruited including 17 males and 11 females with median age of 42.5 years old. The most common CCA/Ph(-)were trisomy 8 (60.7%), monosomy 7 (14.3%). 64.3% CCA/Ph(-)were transient and 35.7% recurrent (more than 2 times). Cytopenia in two or three lineages of peripheral blood was seen in 42.9% patients. As to the efficacy, 89.3% patients achieved major cytogenetic response (MCyR), 25% with major molecular response (MMR). The median follow-up time was 26.5 months. Treatment failure (TF) of TKI occurred in 32.1% patients with median duration of response 8 (1-41) months. Univariate analysis showed that TF rate was significantly correlated with the frequency of CCA/Ph(-)and cytopenia (all P<0.05). The MMR rate was also significantly correlated with cytopenia (P<0.05). Cytopenia of two lineages or pancytopenia was an independent risk factor related to MMR rate (RR=3.868, 95%CI 1.216-12.298, P=0.022) . Conclusions: Cytopenia in CCA/Ph(-)appears to be an independent risk factor of MMR in CML patients with TKI treatment. The recurrent CCA/Ph(-)may link to higher treatment failure rate. Drug withdrawal or alternative strategy should be considered according to response and the ABL kinase mutations.

1099P - BCR-ABL transcript variant’s significance in chronic myeloid leukemia in chronic phase: Institutional experience from a developing country

BackgroundChronic myeloid leukemia (CML) is a malignant clonal hematopoietic disorder characterized by a translocation between chromosomes 9 and 22 leading to the production of BCR-ABL fusion protein. This fusion produces mainly two variants, namely b3a2 and b2a2, rarely are other transcripts detected. To date, the exact role of these transcript variants are unknown and has shown mixed results. The objective of this study is to study the clinical-hematological profile and major molecular response rates (MMR) at 1 year in relation to b2a2 and b3a2 transcripts in CML-CP. MethodsAfter approval from the institutional ethics committee, the data of patients attending medical oncology department from January 2014 to December 2015 (2 years) were collected and analyzed. A total of 154 patients were diagnosed with CML and 140 of them were in chronic phase (CP). ResultsAmong 140 patients, males accounted for 88 (62%) and b3a2 type was seen in 99 patients (71%). Baseline parameters like hemoglobin, white cell count, platelet count, Sokal scoring, and EUTOS risk are shown in Table below. Follow up data was not available for 2 and 9 patients in b2a2 and b3a2 type, respectively.*SEM: Standard Error of Mean After 1 year of therapy with imatinib, 63% in b2a2 and 52% in b3a2 type achieved MMR (p-value 0.21). Twenty patients (14%) were evaluated for kinase domain resistance mutations (17 in b3a2 and 3 in b2a2). Seven out of 17 patients in b3a2 and none in b2a2 type had detectable mutations. Phase migration to accelerated or blast phase occurred in 3 (7%) and 9 (9%) in b2a2 and b3a2 transcript types, respectively.Table: 1099PTable: 1099PParameter (N=140)B2a2 (n=41)B3a2 (n=99)P valueMean Hemoglobin mg/dl SEM9.6 0.319.8 0.20.6 NSMean Total Leucocyte Count (X109) SEM166 16.3185 9.80.3 NSMean Platelet Count (X109) SEM379 3.57440 2.420.16 NSSokal risk (%) Low Intermediate High3 (7) 20 (49) 18 (44)7 (7) 40 (40) 52 (53)0.63 NSEUTOS risk (%) Low High12 (30) 29 (70)53 (52) 47 (47)0.011 SignificantMMR at 1 year (%)63520.21NS*SEM: Standard Error of Mean After 1 year of therapy with Imatinib, 63% in b2a2 and 52% in b3a2 type achieved MMR (p-value 0.21). Twenty patients (14%) were evaluated for kinase domain resistance mutations (17 in b3a2 and 3 in b2a2). Seven out of 17 patients in b3a2 and none in b2a2 type had detectable mutations. Phase migration to accelerated or blast phase occurred in 3 (7%) and 9 (9%) in b2a2 and b3a2 transcript types respectively. ConclusionsThere is no statistically significant difference between the two transcripts in relation to baseline hematological parameters. Patients with b2a2 type had higher EUTOS score at presentation. Despite this, at the end of 12 months, MMR rates were similar between b2a2 and b3a2 transcript types. Legal entity responsible for the studySiva K Prasad. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

A multicenter, randomized phase III study of asciminib (ABL001) versus bosutinib in patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP) previously treated with ≥2 tyrosine kinase inhibitors (TKIs).

TPS7070 Background: There is a need for new treatment options for pts with CML who are intolerant/resistant to currently available BCR-ABL1 ATP-binding site targeted TKIs. Asciminib is a potent and specific BCR-ABL1 inhibitor with a novel allosteric mechanism of action targeting the ABL1 myristoyl pocket. This results in a mutation-driven resistance profile different from that of ATP binding-site TKIs, providing potential for both monotherapy and combination therapy with ATP-binding-site TKIs. In a phase 1 study (NCT02081378), asciminib showed clinical activity and good safety/tolerability in CML pts with resistance/intolerance to ≥2 TKIs and in pts with the T315I mutation. The recommended dose for asciminib monotherapy in CML pts without the T315I mutation was established as 40 mg BID. An ongoing phase 3 study (NCT03106779) is evaluating asciminib monotherapy vs bosutinib in pts with CML who have been treated with ≥2 prior ATP-binding-site TKIs. Methods: Eligible pts are adults with CML-CP who previously received ≥2 TKIs, with intolerance or failure to the most recent TKI. Treatment failure is defined per 2013 European LeukemiaNet (ELN) recommendations. Pts harboring T315I or V299L mutations are excluded. Pts are randomized 2:1 – stratified by baseline cytogenetic response status – to receive asciminib 40 mg BID or bosutinib 500 mg QD (planned enrollment: N = 222). Primary and key secondary objectives are to compare the rate of major molecular response ( BCR-ABL1IS≤0.1%) with asciminib vs bosutinib at 24 and 96 weeks, respectively. In a recent protocol amendment, the baseline BCR-ABL1IS threshold for enrollment was lowered from ≥1% to &gt; 0.1% for pts with intolerance to the most recent TKI. This change was implemented to align with clinical practice and satisfy the treatment need to avoid waiting for an increase in BCR-ABL1IS levels to ≥1%. In addition, pts with documented bosutinib treatment failure as per ELN recommendations may switch to receive asciminib therapy at any time, as such pts may have limited treatment options outside of this study. This study is ongoing with 149 participating study sites in 30 countries. Clinical trial information: NCT03106779.

Frontline flumatinib versus imatinib in patients with chronic myeloid leukemia in chronic phase: Results from the China randomized phase III study.

7004 Background: Flumatinib (FM), a derivative of imatinib (IM), is a novel BCR-ABL1 tyrosine kinase inhibitor (TKI). The aim of this open-label phase III study was to validate the efficacy and safety of FM in comparison with IM as frontline treatment in Chinese patients with newly diagnosed Philadelphia chromosome–positive chronic myeloid leukemia (CML) in chronic phase (CML-CP). Methods: Randomization was stratified by Sokal score with a 1:1 allocation to each arm. Primary endpoints were major molecular response (MMR = BCR-ABL IS≤0.1%) rates at 6 and 12 months. Molecular responses were assessed at a central laboratory blinded to treatment allocations during the study. Efficacy endpoints were analyzed for the intention-to-treat populations. This study is registered with ClinicalTrials.gov, number NCT02204644. Results: 400 eligible patients were randomized and patient characteristics at baseline were similar in each arm. The full analysis set (FAS) consisted of 393 patients who received FM 600 mg (n = 196) or IM 400 mg (n = 197) tablets once daily. Compared with IM, FM resulted significantly higher induction of MMR rate (%; 95%CI) at 6 month (33.7; 27.06-40.29 vs 18.3; 12.88-23.67; P = 0.0005) and 12 month (48.5; 41.47-55.47 vs 33.0; 26.43-39.56; P = 0.0021) and also at 3 month (8.2; 4.33- 12.00 vs 2.0; 0.06-4.00; P = 0.0058). Significantly more patients in the FM than in the IM arm achieved a complete molecular response (BCR-ABL IS≤0.0032%) at 12 months. Early molecular response (BCR-ABL IS ≤ 10%) at 3 months and early CCyR at 6 months were also significantly higher with FM than IM (82.1; 76.78-87.50 vs 53.3; 46.33-60.27; P &lt; 0.0001 and 60.71; 53.88-67.55 vs 49.75, 42.76, 56.73; P = 0.0332). FM has a safety profile similar to IM. The rates of grade 3/4 TEAEs of FM were similar to IM, 56.57% (112 of 198) vs 41.38% (87 of 196). However, the frequencies of some nonhematological and hematological adverse events were significantly lower in the FM than in the IM arm, such as rash (4.59% vs 12.63%, P = 0.0064) and eyelid edema (0.51 vs 14.65, P &lt; 0.0001); leukopenia (30.61 vs 62.63, P &lt; 0.0001) and neutropenia (30.10 vs 59.60, P &lt; 0.0001). No specific TEAE was identified in each arm. Conclusions: This phase III study met its primary endpoints. Our study results suggest that FM is comparable to IM in its safety and superior in its efficacy profile at 3, 6 and 12 month time points. These results support FM as a frontline treatment option for patients with newly diagnosed CML-CP. Clinical trial information: NCT02204644.

Responses to Dasatinib as a Second- and Third-Line Tyrosine Kinase Inhibitor in Chronic Phase Chronic Myeloid Leukaemia Patients

We retrospectively evaluated the efficacy and safety of dasatinib among 48 Chinese patients with chronic phase chronic myeloid leukaemia. The proportions of patients achieving the optimal molecular responses at 3, 6, and 12 months, a major molecular response (MMR) rate and a complete cytogenetic response (CCyR) rate were 87.0, 87.0, 72.2, 45.8, and 72.7% for patients with dasatinib as second-line therapy, and 34.8, 34.8, 33.3, 20.8, and 46.2% as third-line therapy, respectively. A BCR-ABL1 transcript level on the International Scale (BCR-ABL1^IS) of ≤10% at the initiation of ­dasatinib treatment was found to be associated with a higher probability of achieving MMR. Among patients with a ­BCR-ABL1^IS higher than 10% at initiation of dasatinib treatment, dasatinib showed better performance as a second-line therapy than as a third-line therapy. The patients who achieved an optimal molecular response at 3 months had a superior cumulative incidence of MMR and CCyR compared with patients who failed to achieve such a response. Dasatinib induced considerable responses as a second-line treatment, especially in patients with a BCR-ABL1^IS ≤10% at initiation of treatment, whereas the efficacy was limited in patients receiving third-line therapy with a BCR-ABL1^IS >10% at the initiation of treatment.

The Outcomes of Chronic Myeloid Leukemia Patients With Molecular Warning Responses During Imatinib Treatment According to the European LeukemiaNet 2013 Recommendations

BackgroundIn the European LeukemiaNet (ELN) 2013 recommendations, chronic myeloid leukemia (CML) patients with warning response (WR) were suggested to be monitored closely continuing with the same tyrosine kinase inhibitor (TKI). Differently, the guidelines of the National Comprehensive Cancer Network considers switching to another TKI as an option. Patients and MethodsWe retrospectively evaluated 73 CML patients receiving first-line imatinib, who were followed and managed in accordance with ELN recommendations. We compared patients with molecular WR with patients with optimal response (OR) and failure regarding short- and long-term outcomes. ResultsThe cumulative major molecular response (MMR) rates in patients with OR were significantly higher at any time point than those achieved by the WR group. Patients with WR at 3 months had significantly inferior failure-free survival (FFS) than optimal responders, but overall survival (OS) was similar. For 6 and 12 months, the WR and OR groups had similar FFS and OS. Twenty of 23 patients with WR at 12 months achieved MMR during imatinib treatment. ConclusionIt takes longer to get to ELN time points with imatinib than second-generation TKIs (2GTKIs). Treatment might fail in a small proportion of the patients with WR during imatinib treatment, but close and careful monitoring and timely switching to 2GTKIs might translate into favorable outcomes. Avoiding early switch to 2GTKIs would prevent patients from experiencing potential toxicities. There is still a need for prospective comparative studies (ie, continuing imatinib treatment vs. switching to 2GTKIs) in patients with WR, to justify the validity of this response category and to explore the benefit of treatment change in these patients.

Management using the plasma concentration of tyrosine kinase inhibitors for the treatment of chronic myelogenous leukemia: an update

Imatinib, nilotinib, dasatinib, bosutinib, and ponatinib are tyrosine kinase inhibitors used to treat chronic myeloid leukemia (CML). Therapeutic drug monitoring (TDM) and target concentration intervention (TCI) are novel strategies that use concentration-controlled dosing (CCD) to attain a faster and more profound clinical response in patients with CML. The target plasma trough concentration (C0) of imatinib is 1,000 ng/ml to obtain a higher major molecular response (MMR) rate. Target nilotinib and bosutinib C0 of 900 and 62 ng/ml, respectively, are recommended to attain a better response, whereas a target ponatinib C0 of 21.3 ng/ml has been proposed to obtain a better response and decrease the risk of adverse events, such as vascular toxicity. Approaches for these four TKIs involve the use of TCI with specific target concentrations rather than TDM with a therapeutic range. Conversely, for dasatinib, a lower C0 of <4.33 ng/ml is the maximum toxic concentration recommended to avoid pleural effusion. Therefore, precision dosing using CCD of TKIs for CML could maximize the clinical benefit and minimize toxicity.

Impact of Myelofibrosis at Presentation on Outcomes in Chronic Myeloid Leukemia in Chronic Phase

Background:Presence of myelofibrosis on bone marrow examination is considered as poor prognostic factor in patients with chronic myelogenous leukemia (CML). Scant data is available on myelofibrosis, especially in the era of tyrosine kinase therapy. The present study was designed to analyze impact of myelofibrosis on outcomes in newly diagnosed patients with chronic myeloid leukemia in chronic phase (CML-CP).Aims and objectives:The primary objective of this analysis was to study event free survival (EFS) and major molecular response rates (MMR) at one year in patients with CML-CP with myelofibrosis.Secondary objectives were to study the parameters impacting outcomes in patients with CML-CP with myelofibrosisMaterials and methods:Study period: 2010 to 2016Type of study: retrospective analysis.The diagnosis of CML-CP was done by demonstration of BCR-ABL translocation by polymerase chain reaction or fluorescence in situ hybridization. Event free survival was defined as the time from start of therapy to death, transformation to accelerated or blast phase, hematologic resistance or toxicity intolerance. Statistical analysis was done using SPSS software, version 25. Overall survival curves were plotted using the Kaplan-Meier method. Grade of myelofibrosis, EUTOS risk, age and compliance were analyzed on multivariate analyses.Results:Data of 147 patients with CML-CP with myelofibrosis at presentation was retrospectively collected, of which 79(53.7%) were males and 68(46.3%) were females. The baseline characters were tabulated in Table 1. Abdominal fullness (60.5%) was the most common symptom at presentation followed by fatigue (48.9%), weight loss (36.7%), fever (25.1%) and bleeding manifestations (12.9%). EUTOS risk was low in 94(64%) patients and high in 53 (36%) patients. Myelofibrosis grade 1, 2, 3 and 4 were seen in 20(13.6%), 36(24.5%), 38(25.9%) and 27(18.3%) patients respectively. Grade of myelofibrosis was not available in 26(17.7%) patients.Of 147 patients, outcome parameters were available in 92 patients. Of 92 patients, 34(37%) attained MMR at 1 year. At a median follow up of 46 months, event free survival was 60.9%. Of 92 patients, MMR at one year differed significantly in patients with grade 1 and 2 myelofibrosis (48.8%) compared to patients with grade 3 and 4 myelofibrosis (26.5%) (p=0.02). Event free survival was higher in patients with grade 1 and 2 myelofibrosis (76.7%) compared to patients with grade 3 and 4 myelofibrosis (46.9%) (p=0.005). Drug induced myelosuppression was seen in 27(29.3%) patients, of which 7(26%) patients received dose reduction. Phase transformation was seen in 6 patients, of which 1(16.7%) and 5(83.3%) patients were transformed to accelerated phase and blastic phase respectively. On multivariate analysis, only grade of myelofibrosis had significant impact on event free survival(p=0.013).Conclusion:In patients with newly diagnosed CML-CP, major molecular response was significantly lower for those with higher grade of myelofibrosis. Grade of myelofibrosis at presentation had significant impact on outcomes in CML-CP. Hence, bone marrow examination for presence and grade of myelofibrosis helps in prognosticating CML-CP patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Final Study Results of Newly Diagnosed Chronic Myeloid Leukemia Chronic Phase (CML-CP) Patients Receiving Radotinib 300 Mg BID or Imatinib: Rerise 48 Months Follow-up

Background: In RERISE phase 3 study, radotinib demonstrated significantly higher and faster rates of major molecular response (MMR) than imatinib in patients with newly diagnosed CML-CP. By 36 months follow up, MMR (BCR-ABL1IS ≤ 0.1%) and MR4.5 (BCR-ABL1IS ≤ 0.0032%) in radotinib 300 mg twice daily (bid) were higher than imatinib group. Also, early molecular response (EMR) at 3 months could predict better long term outcomes in both radotinib and imatinib groups. Here, authors updated 48 months long-term benefits and risks of 300mg bid and imatinib 400mg qd from RERISE phase 3 study (NCT01511289).Methods: RERISE study was randomized trial of radotinib 300 mg bid (n=79), radotinib 400 mg bid (n=81), or imatinib 400 mg once daily (qd) (n=81) in patients with newly diagnosed CML-CP. We evaluated long-term MMR and MR4.5, overall survival (OS), and progression-free survival (PFS) including safety data by 48 months.Results: At the study completion, 53% of patients with radotinib and 44% of patients with imatinib treated were remained. MMR and MR4.5 continued to be higher in patients receiving radotinib 300 mg bid compared with imatinib 400mg qd (Table). Especially, MMR rate by 48 months was significantly higher for radotinib compared to imatinib (76% vs 56%; P=0.0070, Figure). Also, early molecular response (EMR) at 3 months were observed in 86% of patients in the radotinib 300 mg bid group and 68% in the imatinib group (P = 0.0179). More patients treated with radotinib 300mg bid who had EMR at 3 months achieved MMR and MR4.5 by 48 months: 84% and 53% in the radotinib 300 mg bid group and 71% and 44% in the imatinib group, respectively. 48 months estimated OS and PFS rate were not significantly different in two groups (99% vs 94%; P=0.3224, 97% vs 94%; P=0.4328). Treatment failure was lower in radotinib group compared with imatinib group (Table).The safety profiles were consistent with those previously reported and most of adverse events (AEs) developed within 12 months. No new or unexpected safety events were reported in both arms by 48 months and no serious CVE related with radotinib reported.Conclusions: With a minimum 48 months follow-up, radotinib continued to demonstrate higher rates of MMR and MR4.5 than imatinib in newly diagnosed CML-CP. Also, these responses with radotinib were earlier and deeper compared with imatinib. Up to 48 months, no new and serious safety events related with radotinib reported. These results demonstrate that radotinib may have higher possibility of treatment- free remission (TFR) on frontline therapy as well as it can be one of the standards of care in newly diagnosed CML-CP. [Display omitted] DisclosuresBunworasate:IL-YANG: Research Funding. Comia:IL-YANG: Research Funding. Mun:IL-YANG: Research Funding. Caguioa:IL-YANG: Research Funding. Kim:Pfizer: Research Funding; Novartis: Research Funding; BMS: Research Funding; Ilyang: Research Funding.

One Size May Not Fit All for TKI Dosing in Chronic Phase CML—Deep Molecular Responses Despite Dose Reduction

AbstractBackground: The development of tyrosine kinase inhibitors (TKIs) has dramatically changed the landscape of chronic myelogenous leukemia (CML) treatment. Dosing of TKIs is based on the phase of disease at presentation, but is not altered based on body surface area (BSA), gender, or other patient characteristics. Although TKIs are generally well tolerated, lower grade hematologic and non-hematologic toxicities are not infrequent. Inability to maintain dosing during the first year of therapy (missing as few as 10% of doses per month) has been associated with lower rates of major molecular response (MMR), which might have survival implications and/or prevent treatment-free remission attempts. While the package insert of three TKIs (imatinib, dasatinib, nilotinib) commonly used in first line therapy provides specific dose-reduction instructions for hematologic toxicity, only nilotinib has recommendations for non-hematologic toxicities. Long-term outcome data on the effects of dose-reduction of TKI therapy based on toxicity is lacking. Furthermore, there is little data on risk factors for TKI intolerance. Thus, we sought to identify characteristics of patients requiring dose reductions as a part of first-line TKI treatment for chronic phase CML who successfully achieved an MMR 4 or greater as well to determine the long-term outcome of these patients in a retrospective fashion.Methods: Using electronic medical records, we identified patients seen at the John Theurer Cancer Center for treatment of newly diagnosed chronic phase CML between November 1, 2012 and July 1, 2016 who had successfully achieved an MMR 4 or greater. These records were screened for individuals requiring chronic dose reductions as part of first-line treatment for chronic phase CML. We identified 35 consecutive patients that were able to tolerate full dose TKI therapy per package insert. This control group was used to determine risk factors for TKI intolerance compared to patients that required dose reduction.Results: A total of 20 patients were identified who achieved an MMR 4 or greater and required long-term dose reduction of first-line TKI therapy with a median follow up of 48.5 months (range 18.7-172.6). The median time on full dose therapy prior to dose reduction was 7.7 months (range 0-40.2). The median time spent on reduced dose therapy was 43.5 months (range 12.1-159.0). The time to MMR was 8.3 months (1.8-40.2). The majority of patients remained in MMR 4 despite maintenance on dose reduction. Median progression free survival (PFS), as defined by loss of MMR, of dose-reduced patients had not yet been reached. One, two, and three year PFS rates were 100%, 95.0%, and 88.7% respectively. When compared to the control group of patients tolerating front line therapy at full-dose, patients requiring dose reduction were more likely to be female: 80% vs 46% (P=0.028) and have a lower BSA: 1.78 versus 2.03 mg/m2 (P=0.0014). Other variables including age, TKI, Sokol score, and performance status were similar in both groups.Discussion: Among patients who achieved MMR4 or greater on first-line therapy, we noted that female sex and lower BSA were risk factors for TKI dose reduction. Based on the available control group, it cannot be determined if either of these are independent variables. This retrospective analysis demonstrates many patients are able to successfully achieve and maintain a deep molecular response with reduced doses of TKI therapy and perhaps provides justification for dose reduction to increase compliance and maximize treatment tolerability. The majority of patients remained in MMR4 despite dose reductions. DisclosuresMcCloskey:Celgene Pharmaceuticals: Consultancy, Speakers Bureau; Takeda Pharmaceuticals: Speakers Bureau; Jazz Pharmaceuticals: Honoraria, Speakers Bureau; Amgen: Speakers Bureau; COTA: Equity Ownership. Stanislaus:Celgene Pharmaceuticals: Consultancy, Speakers Bureau; Takeda Pharmacetucals: Consultancy, Speakers Bureau; Jazz Pharmaceuticals: Speakers Bureau; Novartis Pharmaceuticals: Consultancy, Speakers Bureau. Koprivnikar:Otsuka Pharmaceuticals: Honoraria; Alexion Pharmaceuticals: Consultancy, Speakers Bureau; Amgen Pharmaceuticals: Speakers Bureau; COTA: Equity Ownership.

Bosutinib or Imatinib in Older Vs Younger Patients with Newly Diagnosed Chronic Myeloid Leukemia in the Phase 3 BFORE Trial

Introduction: Bosutinib is approved for newly diagnosed chronic phase (CP) chronic myeloid leukemia (CML) and CML resistant or intolerant to prior therapy. Efficacy and safety of first-line bosutinib and imatinib were assessed in older vs younger patients in the ongoing phase 3 BFORE trial (NCT02130557). Methods: In all, 536 patients were randomized 1:1 to receive bosutinib or imatinib (400 mg once daily). We compared outcomes in patients aged ≥65 years (older group) vs Results: In the bosutinib arm (n=268), 53 were older and 215 were younger patients. In the imatinib arm (n=268; 3 untreated), 48 (2 untreated) were older and 220 (1 untreated) were younger patients. Sokal risk scores were balanced between treatment arms but higher in the overall older (8.9% low, 70.3% intermediate, 20.8% high) vs younger (44.1% low, 34.7% intermediate, 21.1% high) populations, reflecting that age is part of the score. Bosutinib was discontinued in 32.1% of older and 28.4% of younger patients; the most common primary reason was treatment-related adverse events (AEs; 18.9% and 15.3%, respectively). Imatinib was discontinued in 32.6% of older and 33.8% of younger patients, most frequently due to suboptimal response or treatment failure (13.0% and 13.2%, respectively). The percentage of patients who discontinued treatment due to treatment-emergent AEs (TEAEs) was similar in the older vs younger group in both arms (bosutinib: 22.6% vs 19.1%; imatinib: 8.7% vs 12.3%). In older vs younger patients, median (range) duration of treatment was similar: 24.8 months (0.3-33.3) vs 24.9 months (0.3-33.5) for bosutinib and 25.6 months (2.9-33.1) vs 24.5 months (0.7-33.4) for imatinib. Median relative dose intensity was slightly lower in older vs younger patients in the bosutinib arm (92.8% vs 99.3%) but was 100% in both age groups in the imatinib arm. The difference in rates of major molecular response (MMR) at 12 months (primary endpoint) with bosutinib vs imatinib was consistent across age groups (older: 43.4% vs 35.4%; younger: 47.4% vs 36.4%; P=0.7879 for test of interaction), as was the difference in rates of CCyR by 12 months (older: 68.8% vs 69.0%; younger: 79.3% vs 65.8%; P=0.1689). MR rates at 24 months (and MR1 at 3 months) were generally similar in older vs younger patients within each arm and higher with bosutinib than with imatinib (Table 1). Time to achieve MMR on bosutinib was not different in older vs younger patients (hazard ratio: 1.227; P=0.2380, after adjustment for baseline and time-dependent covariates in a multivariable proportional subdistribution hazards model). Rates of common TEAEs in each treatment arm were similar ( Conclusions: In the phase 3 BFORE trial, bosutinib showed clinical activity in older and younger patients with newly diagnosed CP CML. Difference in rates of MMR at 12 months for bosutinib vs imatinib was consistent in older and younger patients. MR rates at 24 months were similar in older and younger patients and higher with bosutinib than with imatinib. Although the incidence of grade 3/4 TEAEs, serious TEAEs, and dose modifications due to TEAEs were higher in older vs younger bosutinib-treated patients, treatment discontinuation rates were similar between age groups, suggesting that, regardless of patient age, TEAEs were manageable with bosutinib. Disclosures Deininger:Pfizer: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Blueprint: Consultancy. Kota:Pfizer: Honoraria; Xcenda: Honoraria; Novartis: Honoraria; Incyte: Honoraria; BMS: Honoraria. Lipton:Pfizer: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding. Milojkovic:Incyte: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; BMS: Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau. Garcia Gutierrez:Incyte: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Novartis: Honoraria, Research Funding. Leip:Pfizer: Employment, Equity Ownership. Nick:Pfizer: Employment, Equity Ownership. Hochhaus:Takeda: Research Funding; Bristol-Myers Squibb: Research Funding; Novartis: Research Funding; Pfizer: Research Funding; Incyte: Research Funding. Gambacorti-Passerini:BMS: Consultancy; Pfizer: Consultancy, Honoraria, Research Funding. Cortes:Astellas Pharma: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Arog: Research Funding. Brummendorf:Merck: Consultancy; Pfizer: Consultancy, Research Funding; Janssen: Consultancy; Takeda: Consultancy; Novartis: Consultancy, Research Funding.

Comparison of the Clinical Outcomes of Nilotinib and Dasatinib Therapies in Newly Diagnosed Patients in the Chronic Phase of Chronic Myeloid Leukemia: A Retrospective Analysis

Background and Aim: Treatment with a tyrosine kinase inhibitor (TKI) is the standard of care for patients with chronic myeloid leukemia (CML). Based on the results of the ENESTnd and DASISION studies, the European LeukemiaNet 2013 guidelines now recommend the use of TKIs, imatinib (400 mg once daily), nilotinib (300 mg twice daily), and dasatinib (100 mg once daily) as first-line treatment for patients with CML in the chronic phase (CML-CP). Compared to imatinib, the new generation TKIs, nilotinib and dasatinib, were found to have deeper and faster treatment response rates with acceptable toxicities. However, a direct comparison between nilotinib and dasatinib has never been reported previously. Our study aims to compare the outcomes and molecular responses achieved following the first-line use of these two agents in patients with CML-CP.Patients and Methods: The database of the CML Cooperative Study Group, which includes patients who were initially diagnosed with CML after the introduction of imatinib (April 2001), was reviewed, and patients who were given nilotinib or dasatinib as first-line therapy were identified. The event-free survival (EFS, defined as the loss of treatment efficacy, disease progression, or any cause of death), and rates of cumulative major molecular response (MMR), and deep molecular response (DMR, defined as the depth of MR 4.5) were compared between the nilotinib and dasatinib groups. Further, the predictive ability of the Sokal, Hasford, and European Treatment and Outcome Study (EUTOS) scoring systems for the achievement of molecular responses was also evaluated. For the analysis of molecular responses, patients who switched from their initial treatment agent to another TKI before achievement of MMR or DMR were considered to have no MMR or DMR.Results and Discussion: Out of 361 patients with CML-CP enrolled in our database, 58 and 63 were treated with conventional doses of nilotinib (300 mg twice daily) and dasatinib (100 mg once daily), respectively, as first-line therapy. Patients who had been started on a low dose TKI therapy were excluded from this analysis. The patient demographics, including age, sex, observation periods, and the Sokal, Hasford, and EUTOS scores did not show significant differences between the groups. In total, there were five events during the observation period (1 in the nilotinib group and 4 in the dasatinib group), and all events were deaths unrelated to CML, except for one in a patient in the dasatinib group who showed loss of complete cytogenetic response. The disease did not progress to the accelerated or blastic phase in any of the cases. The EFS did not differ between these two groups (p = 0.214). The MMR rates by 6, 12, 18, and 24 months were 59%, 72%, 74%, and 81%, respectively, in the nilotinib group and 52%, 73%, 81%, and 86%, respectively, in the dasatinib group. The DMR rates by 6, 12, 18, and 24 months was 7%, 17%, 24%, and 28%, respectively, in the nilotinib group and 3%, 16%, 25%, and 29%, respectively, in the dasatinib group. During the first 24 months of treatment, 4 (7%) patients in the nilotinib group and 11 (17%) in the dasatinib group had been switched to other TKIs (p = 0.0983). Among the three scoring systems, only the Hasford score could predict the achievement of DMR, and all of them failed to predict the achievement of MMR in the entire cohort. Our data suggest that both nilotinib and dasatinib have comparable efficacies, with high molecular response rates and promising outcomes. The validity of our findings should be tested in a randomized study, which is currently underway in Japan. DisclosuresTakaku:Bristol-Myers Squibb: Honoraria, Speakers Bureau; Novartis Pharma K.K.: Honoraria, Speakers Bureau. Tokuhira:Mitsubishi Tanabe Pharma Corporation: Speakers Bureau; Bristol-Myers Squibb: Speakers Bureau; AYUMI Pharmaceutical Corporation: Speakers Bureau; Chugai: Speakers Bureau. Asou:Eisai Co., Ltd.: Research Funding; SRL Inc.: Consultancy; Yakult Honsha Co., Ltd.: Speakers Bureau; Kyowa Hakko Kirin Co., Ltd.: Speakers Bureau; Asahi Kasei Pharma Co., Ltd.: Research Funding; Astellas Pharma Inc.: Research Funding; Sumitomo Dainippon Pharma Co., Ltd.: Research Funding; Chugai Pharmaceutical Co., Ltd.: Research Funding. Kizaki:Nippon Shinyaku,: Research Funding, Speakers Bureau; Celgene: Research Funding, Speakers Bureau; Bristol-Myers Squibb: Research Funding, Speakers Bureau; Novartis: Speakers Bureau. Kawaguchi:Novartis Pharma K.K.: Honoraria, Speakers Bureau; Bristol-Myers Squibb: Honoraria, Speakers Bureau; Alexion: Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau.

Nilotinib (Tasigna®) and Low Intensity Chemotherapy for First-Line Treatment of Elderly Patients with BCR-ABL1-Positive Acute Lymphoblastic Leukemia: Final Results of a Prospective Multicenter Trial (EWALL-PH02)

Background. Tyrosine kinase inhibitors (TKI) are standard front-line therapy for patients with BCR-ABL1/Philadelphia positive ALL (Ph+ ALL), but the relative merits of available TKIs remain uncertain. Nilotinib is a potent inhibitor of BCR-ABL1 with broader activity against ABL kinase domain mutations than imatinib and greater selectivity than dasatinib or ponatinib. As there is a paucity of data on nilotinib as first-line therapy for Ph+ ALL, the EWALL (European Working Group for Adult ALL) conducted an international clinical trial to evaluate efficacy and safety of the combination of nilotinib with low intensity chemotherapy.Patients and Methods. After a prephase with dexamethasone (DEX) and cyclophosphamide, nilotinib (400 mg BID) was given concurrently with the same chemotherapy backbone employed in the EWALL-PH01 assessing the combination with dasatinib (Rousselot et al, Blood 2016;128:774-82). Induction consisted of nilotinib combined with weekly vincristine (VCR, 1mg iv) and oral dexamethasone 40mg 2 days (20 mg over 70y). Nilotinib was continued throughout six consolidation cycles, followed by 24 months maintenance therapy with nilotinib, 6-MP, MTX and DEX/VCR boosts. Stem cell transplantation (SCT) was permitted as considered appropriate. BCR-ABL1 RTQ-PCR and kinase domain resistance mutations were centrally monitored. Primary endpoint was event-free survival (EFS) at 12 months, secondary endpoints included rates of CR, major and complete molecular response, relapse free survival (RFS), EFS and overall survival (OS).Results. 72/79 enrolled pts. were evaluable for response, 3 withdrew consent, 4 did not meet eligibility criteria. Median age was 65.5 (55-85) years, male/female ratio 0.85, ECOG status 0 or 1 in 89% of pts., median CIRS comorbidity score 5(0-19). Baseline vascular risk factors including high blood pressure (grade ≥2) were present in 36% of pts.. Sixty-eight of 72 pts. (94.4%) achieved CR, one died during induction and one was refractory, 2 pts. discontinued study therapy. Non-hematologic adverse events (AE) grades 3/4 during induction (in ≥ 5% of pts. irrespective of causality) included infections (n=20), elevated transaminases or bilirubin (n=18) and gastrointestinal AEs (n=12). The spectrum of AEs was similar during consolidation, without concerns related to cardiovascular events. 24 pts. (61y; 55-69y) underwent allogeneic (9 MUD, 12 SIB, 3 Haplo) and 3 autologous SCT. 21 pts. received reduced intensity conditioning (including 8Gy TBI, n=11) regimens. Among all pts., relapse was the main cause of treatment failure (n=23; 17 BM, 2 CNS, 3 other sites, 1 na), 11 pts. died in CR (6 after HSCT), 34 are in ongoing CR. Based on Kaplan Meier analysis, EFS (events being resistant disease, relapse or death) at 12 months was 74%, with median follow-up of 39 (24-66) months for surviving pts., EFS and OS at 4 years was 42%, and 47%, respectively. By landmark analyses using median time to HSCT as cutoff, cumulative incidence of relapse in transplanted vs. non-transplanted pts. was 32% and 47%, OS at 4 years was 61% and 39%, median OS was not reached versus 3.6 years, respectively (p=ns). The proportion of pts. with a BCR-ABL1/ABL1 ratio ≤0.1% increased from 41% after induction to 86% after consolidation 2; that of pts. with undetectable or non-quantifiable BCR-ABL1 transcripts (sensitivity ≥10-4) increased from 14% to 58%.Conclusions. Nilotinib combined with low-intensity chemotherapy is well tolerated and highly effective in elderly pts. with Ph-positive ALL. OS and EFS compare favorably with previous similar studies testing imatinib or dasatinib. With 32% of pts. undergoing allogeneic HSCT and 61% survival at 4 years, transplantation is a viable option in this elderly cohort of pts.. DisclosuresOttmann:Celgene: Consultancy, Research Funding; Novartis: Consultancy; Incyte: Consultancy, Research Funding; Takeda: Consultancy; Amgen: Consultancy; Pfizer: Consultancy; Fusion Pharma: Consultancy, Research Funding. Pfeifer:Novartis: Research Funding. Cayuela:Cepheid: Other: financial sponsor to attend John Goldman Conference 2017. Viardot:Roche: Consultancy, Honoraria; Amgen: Consultancy; Gilead Kite: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. Sanhes:Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Goekbuget:Pfizer: Consultancy, Other: Travel support, Research Funding; Novartis: Consultancy, Other: Travel support, Research Funding; Celgene: Consultancy; Kite / Gilead: Consultancy; Amgen: Consultancy, Other: Travel support, Research Funding. Dombret:Jazz Pharma: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Menarini: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Sunesis: Consultancy, Honoraria; Ambit (Daiichi Sankyo): Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Agios: Consultancy, Honoraria; Kite Pharma: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding, Speakers Bureau; Abbvie: Consultancy, Honoraria; Roche/Genentech: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Ariad (Incyte): Consultancy, Honoraria, Other: Travel expenses, Research Funding, Speakers Bureau; Shire-Baxalta: Consultancy, Honoraria; Immunogen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Other: Travel expenses, Speakers Bureau; Cellectis: Consultancy, Honoraria, Other: Travel expenses; Otsuka: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Other: Travel expenses, Research Funding, Speakers Bureau.

Impact of Diarrhea on Health-Related Quality of Life: Analysis of the Phase 3 BFORE Trial of Bosutinib Vs Imatinib for Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia

Introduction: In the ongoing phase 3 BFORE trial (NCT02130557), a significantly higher major molecular response rate at Month 12 was seen with bosutinib vs imatinib in patients with newly diagnosed chronic phase chronic myeloid leukemia (CP CML), and bosutinib treatment was accompanied by improvement or maintenance of health-related quality of life (HRQoL), as assessed by the patient-reported Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) instrument. Diarrhea is a common side effect of bosutinib and occurred more frequently in bosutinib- vs imatinib-treated patients in the primary analysis of the BFORE trial (all grades: 70.1% vs 33.6%). Here, the impact of diarrhea, specifically on HRQoL, was assessed in patients receiving bosutinib or imatinib in the BFORE trial.Methods: Patients with CP CML were randomized 1:1 to receive first-line bosutinib or imatinib. HRQoL was analyzed in the modified intent-to-treat (mITT) population, comprised of Philadelphia chromosome-positive patients with typical BCR-ABL transcripts. The FACT-Leu consists of the 27-item FACT-General (FACT-G) scale with 4 domains (physical, social, emotional, and functional well-being) and the 17-item leukemia-specific subscale; higher scores and changes in scores indicate better HRQoL. Patients completed questionnaires at baseline, every 3 months for the first 2 years and every 6 months thereafter while on treatment, and at treatment completion. In this post hoc analysis, FACT-Leu scores from the first 12 months of treatment were analyzed in patients with diarrhea (any event during treatment) or chronic diarrhea (event lasting ≥28 days). Longitudinal analyses were conducted and standardized effect sizes were calculated to characterize the strength of effect on the FACT-Leu scores for the diarrhea and chronic diarrhea subgroups. Standardized effect sizes of approximately 0.1, 0.2, 0.5, and 0.8 (in absolute values) were considered trivial, small, medium, and large, respectively.Results: In the mITT population (bosutinib: n=246; imatinib: n=241), 163 (66.3%) patients in the bosutinib arm and 74 (30.7%) in the imatinib arm had diarrhea and were evaluable for HRQoL; 34 (13.8%) and 20 (8.3%), respectively, had chronic diarrhea (≥28 days). Among patients who developed diarrhea, the FACT-Leu total score and most subscale scores improved from baseline to Month 12 in both treatment arms, although changes were generally not significant (P>0.05) and could be interpreted as small or trivial, based on effect size (Table). For patients with diarrhea in the bosutinib arm, changes from baseline in the leukemia-specific subscale could be characterized as small improvements starting at Month 6 of treatment; in the imatinib arm, an improvement was not seen until Month 12, and all changes could only be characterized as trivial (Figure). Among patients with chronic diarrhea, the changes from baseline at Month 12 were not significant for all FACT-Leu total or subscale scores in the bosutinib arm and could be interpreted as small or trivial; in the imatinib arm, changes from baseline in all FACT-Leu scores were numerically negative and nonsignificant with the exception of the physical well-being domain (P<0.01), which had a large effect size (Table). For patients with chronic diarrhea in the bosutinib arm, improvements in the leukemia-specific subscale at Month 3 through Month 9 could be characterized as small; in the imatinib arm, a deterioration was seen at Month 3 through Month 12, and changes could be considered small at Months 9 and 12 (Figure).Conclusions: In this post hoc analysis of the BFORE trial, HRQoL was not negatively affected by diarrhea or chronic diarrhea in the bosutinib arm. Although the analysis is limited by the small number of patients, chronic diarrhea during treatment with imatinib appeared to have a greater impact on HRQoL than chronic diarrhea during treatment with bosutinib, based on the magnitude of the effect sizes and direction of changes, particularly for physical well-being. These data suggest that patients with CP CML treated with bosutinib can preserve or slightly improve HRQoL during therapy, regardless of the presence of diarrhea or chronic diarrhea. [Display omitted] DisclosuresBrümmendorf:Merck: Consultancy; Janssen: Consultancy; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Takeda: Consultancy. Mamolo:Pfizer: Employment, Equity Ownership. Reisman:Pfizer: Employment, Equity Ownership. Bushmakin:Pfizer: Employment, Equity Ownership. Cappelleri:Pfizer: Employment, Equity Ownership. Crescenzo:Pfizer: Employment. DeAnnuntis:Pfizer Inc: Employment, Equity Ownership. Viquiera:Pfizer: Employment, Equity Ownership. Cortes:Novartis: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Astellas Pharma: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Arog: Research Funding.

Molecular monitoring of therapeutic milestones and clinical outcomes in patients with chronic myeloid leukemia.

In the current study, the authors determined whether adhering to molecular monitoring guidelines in patients with chronic myeloid leukemia (CML) is associated with major molecular response (MMR) and assessed barriers to adherent monitoring. Newly treated patients with CML from the Quebec province-wide CML registry from 2005 to 2016 were included. Timely polymerase chain reaction (tPCR) was defined as the molecular assessment of BCR-ABL1 at the 3-month, 12-month, and 18-month time points from the initiation of tyrosine kinase inhibitor (TKI) therapy. The cohort was analyzed as a nested case-control study. Cases with a first-ever MMR (BCR-ABL1 ≤0.1%, assessed at any time during follow-up) were matched to up to 5 controls by duration of TKI therapy, volume of patients with CML at the treatment center, year of cohort entry, and age. Odds ratios (ORs) for the performance of tPCR and MMR were adjusted for sex, comorbidities, type of TKI, and other important covariates. The cohort included 496 patients. Of 392 MMR events, 67.9% occurred before 18 months. The performance of tPCR was associated with a doubling of the MMR rate (OR, 2.23; 95% confidence interval [95% CI], 1.56-3.21) and was similar with 1 to 3 tPCRs performed (P = .67). Furthermore, tPCRs at 3 months (OR, 2.77; 95% CI, 1.81-4.23) and 12 months (OR, 3.00; 95% CI, 1.64-5.49) were associated with achieving early MMR, whereas tPCRs at 18 months were not (OR, 1.23; 95% CI, 0.80-1.89). Low-volume centers were found to have lower adherence to tPCR (OR, 0.60; 95% CI, 0.40-0.89). Timely molecular assessment at 3 months and 12 months appears to benefit patients with CML. Adherence to timely monitoring should be encouraged, especially in low-volume treatment centers.