CML-023: Relationship Between High Body Mass Index (BMI) and Treatment Outcomes in Patients with Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Treated with Dasatinib or Imatinib: Retrospective Analysis of the Phase 3 DASISION Trial

2020 ◽  
Vol 20 ◽  
pp. S230
Author(s):  
Massimo Breccia ◽  
Jorge E. Cortes ◽  
Neil P. Shah ◽  
Giuseppe Saglio ◽  
Antonio Jiménez-Velasco ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Chronic Myeloid Leukemia ◽  
Treatment Outcomes ◽  
Retrospective Analysis ◽  
Body Mass ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
High Body Mass Index ◽  
Newly Diagnosed ◽  
Phase 3

The effect of body mass index on efficacy and safety of bosutinib or imatinib in patients with newly diagnosed chronic myeloid leukemia.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7037-7037
Author(s):  
Tim H. Brümmendorf ◽  
Jorge E. Cortes ◽  
Lambert Busque ◽  
Carlo Gambacorti-Passerini ◽  
Leif Stenke ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Chronic Myeloid Leukemia ◽  
Body Mass ◽  
Myeloid Leukemia ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Dose Intensity ◽  
Molecular Response ◽  
Newly Diagnosed ◽  
Efficacy And Safety

7037 Background: Bosutinib (BOS) is approved for the treatment (Tx) of Philadelphia chromosome–positive (Ph+) chronic myeloid leukemia (CML) resistant/intolerant to prior therapy and newly diagnosed Ph+ chronic phase (CP) CML. Body mass index (BMI) was shown to influence Tx response with front-line dasatinib vs imatinib (IMA). We report the efficacy and safety of BOS and IMA by BMI in patients (pts) with newly diagnosed CP CML. Methods: In the open-label BFORE trial, pts were randomized to receive 400 mg once daily BOS or IMA. Outcomes were assessed according to baseline BMI ≥25 or = 25 kg/m2. This post hoc analysis was based on the final 5-y analysis (database lock: June 12, 2020). Results: In the BOS and IMA arms, respectively, 149 (56.4%) vs 115 (43.6%) pts and 145 (54.3%) vs 122 (45.7%) pts had BMI ≥25 vs = 25. In both the BOS and IMA arms, median Tx duration and time on study was 55 mo for pts with BMI ≥25 or = 25; respective median dose intensity was 394 vs 393 mg/d and 400 vs 400 mg/d. Molecular response (MR) rates are shown in the table. Cumulative incidence of major MR was similar in pts with ≥25 vs = 25 receiving BOS (HR 0.99; 95% CI 0.74−1.31) or IMA (HR 1.09; 95% CI 0.81−1.47). Event-free survival (EFS) and overall survival (OS) rates at 60 mo are shown in the table. Most common reasons for Tx discontinuation were adverse events (AEs) (BOS 28.2 vs 20.0%; IMA 13.3 vs 10.7%) and lack of efficacy (BOS 5.4 vs 5.2%; IMA 16.1 vs 19.8%). In pts with BMI ≥25 vs = 25, dose reductions and interruptions due to Tx-emergent AEs (TEAEs) occurred in 43.6 % vs 46.2% and 66.4% vs 69.7% of pts with BOS and 24.5% vs 24.6% and 40.6% vs 50.8% with IMA. Any grade TEAEs in ≥30% of pts with BMI ≥25 vs = 25 were diarrhea (73.8 vs 73.1%), nausea (40.9 vs 31.9%), thrombocytopenia (30.9 vs 41.2%), increased alanine (37.6 vs 28.6%) and aspartate aminotransferase (30.2 vs 20.2%) with BOS and diarrhea (49.0 vs 29.5%), nausea (46.2 vs 37.7%), muscle spasms (33.6 vs 26.2%), neutropenia (14.7 vs 32.0%) and thrombocytopenia (10.5% vs 30.3%) with IMA. Conclusions: Efficacy of BOS was consistent in pts with BMI ≥25 or = 25; however, with IMA a low (vs high) BMI appeared to be associated with worse survival outcomes. Differences in certain TEAEs were observed between BMI subgroups in both treatment arms. Clinical trial information: NCT02130557. [Table: see text]

Delayed Cytogenetic Response and Reduced Rate of Major Molecular Response Associated to Increased Body Mass Index At Baseline in Chronic Phase Chronic Myeloid Leukemia Patients Treated with Imatinib.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2784-2784
Author(s):  
Massimo Breccia ◽  
Giuseppina Loglisci ◽  
Adriano Salaroli ◽  
Alessandra Serrao ◽  
Paola Volpicelli ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Chronic Myeloid Leukemia ◽  
Median Time ◽  
Body Mass ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Normal Weight ◽  
First Line ◽  
Reduced Rate ◽  
The Impact

Abstract Abstract 2784 Obesity, measured as body mass index (BMI), has been identified as a possible risk factor for the onset of several solid tumors as well as for chronic myeloid leukemia (CML). To date, no correlations have been reported in this latter disease between BMI at baseline and response to targeted therapies. We refer here on the impact of BMI on clinical response in CML. Three hundred and thirty-nine chronic phase (CP) CML patients treated with imatinib entered the study: 142 patients first received interferon alpha outside clinical trials and were then switched to imatinib for failure. For this group of patients, BMI was collected at the time of start of imatinib. The remaining patients were consecutively treated with imatinib first-line from January 2000 onward. BMI was defined as the individual's body weight divided by the square of his of her height and patients were categorised according to WHO into four categories: underweight (BMI < 18.5), normal weight (BMI 18.5-< 25), overweight (BMI 25-<30) and obese (BMI ≥ 30). All patients were followed according to ELN guidelines. We also analysed 25 CP-CML patients treated frontline with nilotinib. One hundred and fifty-six patients (46%) were categorized as underweight/normalweight, while 183 patients (54%) were classified as overweight/obese. BMI increased with age, with a median age of 29 years in underweight category, 43.4 years in normal weight, 54.9 years in overweight and 62.4 years in obese patients (p=0.001). We did not reveal statistically significant association between BMI and prognostic risk stratification at baseline, even when we used new EUTOS score, or type of BCR/ABL transcript. No statistically significant difference was revealed in terms of overall CCyR rate which was 87% for underweight/normal weight categories compared to 84% for overweight/obese group (p=0.34). If compared to patients with low BMI (< 18.5–25), patients with increased BMI (> 25–40) at diagnosis who received imatinib, showed a significantly longer median time to reach CCyR (6.8 months vs 3.3 months, p=0.01), a reduced rate of MMR (77% vs 58%, p=0.01) which was also achieved in a longer median time (29 months compared to 14 months, p=0.03). At 18 months, molecular kinetics revealed that median BCR-ABL/ABL ratio was 0.6% IS (range 0.001%-2%) in underweight/normal weight group compared to 1.6% IS (range 0.01%-3%) in overweight/obese category (p=0.01). Conversely, no differences were revealed with respect to BMI in patients treated frontline with nilotinib and also patients with increased BMI obtained rapidly CCyR and MMR, with an incidence similar to that of underweight/normal weight patients. These results suggest that CML patients with increased weight at baseline should be followed and carefully monitored if treated with standard dose imatinib frontline for a possible early switch to a second generation TKI or, as an alternative, should preferably be candidate to receive these drugs as a first line therapy. Disclosures: No relevant conflicts of interest to declare.

EPIC: A phase III randomized, open-label study of ponatinib versus imatinib in adult patients with newly diagnosed chronic myeloid leukemia in chronic phase.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS7129-TPS7129
Author(s):  
Jeffrey H. Lipton ◽  
Michael W. N. Deininger ◽  
Stephanie Lustgarten ◽  
Christopher D. Turner ◽  
Victor M. Rivera ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Dropout Rate ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Open Label ◽  
Phase 3 ◽  
Absolute Increase ◽  
Once Daily

TPS7129 Background: The hallmark genetic abnormality of chronic myeloid leukemia (CML), known as the Philadelphia chromosome, generates the BCR-ABL fusion gene; expression of BCR-ABL in hematopoietic stem cells gives rise to CML. Ponatinib is a potent oral pan–BCR-ABL tyrosine kinase inhibitor (TKI) that is active against native and mutated forms of BCR-ABL, including the T315I gatekeeper mutant. Results from the phase 1 and phase 2 studies of ponatinib demonstrated that ponatinib is generally well tolerated and has substantial anti-leukemic activity in patients with CML who are resistant or intolerant to prior TKI therapy, regardless of baseline mutation status. In addition, multivariate analyses suggest that ponatinib has greater activity in younger patients who are less heavily pretreated and have a shorter time since diagnosis. The phase 3 EPIC (Evaluation of Ponatinib vs Imatinib in CML) study is testing the hypothesis that ponatinib is an effective treatment for newly diagnosed chronic phase (CP) CML patients when compared with standard imatinib therapy. Methods: EPIC is a multicenter, international, phase 3, two-arm, open-label trial of ponatinib (45 mg once daily) versus imatinib (400 mg once daily) in patients with newly diagnosed CP-CML. Patients ≥18 years of age with CP-CML (diagnosed within 6 months prior to study entry) and adequate renal, hepatic, and pancreatic function are eligible for enrollment. Enrolled patients are assigned to receive ponatinib or imatinib in a 1:1 fashion, stratified by Sokal Risk score (low vs intermediate vs high). The primary efficacy endpoint for this trial is major molecular response (MMR) rate at 12 months. Secondary endpoints include MMR rate at 5 years, BCR-ABLIS<10% rate at 3 months, CCyR rate at 12 months, progression-free survival, overall survival, and safety. A sample size consisting of 480 patients will provide 90% power to detect a 15% absolute increase in MMR rate at 12 months using an unstratified Fisher exact 2-sided test at an alpha level of 0.05. Assuming a 10% dropout rate, approximately 528 patients will be enrolled. The first patient was enrolled in August 2012. Clinical trial information: NCT01650805.

scholarly journals Dasatinib or imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: 2-year follow-up from a randomized phase 3 trial (DASISION)

Blood ◽  
2012 ◽  
Vol 119 (5) ◽  
pp. 1123-1129 ◽  
Author(s):  
Hagop M. Kantarjian ◽  
Neil P. Shah ◽  
Jorge E. Cortes ◽  
Michele Baccarani ◽  
Mohan B. Agarwal ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Primary Data ◽  
Molecular Response ◽  
Newly Diagnosed ◽  
Phase 3 ◽  
Log Reduction ◽  
Grade 3

Abstract Dasatinib is a highly potent BCR-ABL inhibitor with established efficacy and safety in imatinib-resistant/-intolerant patients with chronic myeloid leukemia (CML). In the phase 3 DASISION trial, patients with newly diagnosed chronic-phase (CP) CML were randomized to receive dasatinib 100 mg (n = 259) or imatinib 400 mg (n = 260) once daily. Primary data showed superior efficacy for dasatinib compared with imatinib after 12 months, including significantly higher rates of complete cytogenetic response (CCyR), confirmed CCyR (primary end point), and major molecular response (MMR). Here, 24-month data are presented. Cumulative response rates by 24 months in dasatinib and imatinib arms were: CCyR in 86% versus 82%, MMR in 64% versus 46%, and BCR-ABL reduction to ≤ 0.0032% (4.5-log reduction) in 17% versus 8%. Transformation to accelerated-/ blast-phase CML on study occurred in 2.3% with dasatinib versus 5.0% with imatinib. BCR-ABL mutations, assessed after discontinuation, were detected in 10 patients in each arm. In safety analyses, fluid retention, superficial edema, myalgia, vomiting, and rash were less frequent with dasatinib compared with imatinib, whereas pleural effusion and grade 3/4 thrombocytopenia were more frequent with dasatinib. Overall, dasatinib continues to show faster and deeper responses compared with imatinib, supporting first-line use of dasatinib in patients with newly diagnosed CML-CP. This study was registered at ClinicalTrials.gov: NCT00481247.

scholarly journals Phase 3 study of nilotinib vs imatinib in Chinese patients with newly diagnosed chronic myeloid leukemia in chronic phase: ENESTchina

Blood ◽  
2015 ◽  
Vol 125 (18) ◽  
pp. 2771-2778 ◽  
Author(s):  
Jianxiang Wang ◽  
Zhi-Xiang Shen ◽  
Giuseppe Saglio ◽  
Jie Jin ◽  
He Huang ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Chinese Patients ◽  
Newly Diagnosed ◽  
Phase 3 ◽  
Key Points ◽  
Safety Signals

Key Points Chinese patients with newly diagnosed CML-CP achieved higher rates of MMR with nilotinib vs imatinib. Nilotinib was well tolerated, and no new safety signals were observed.

scholarly journals Safety of bosutinib versus imatinib in the phase 3 BELA trial in newly diagnosed chronic phase chronic myeloid leukemia

2014 ◽  
Vol 89 (10) ◽  
pp. 947-953 ◽  
Author(s):  
Carlo Gambacorti‐Passerini ◽  
Jorge E. Cortes ◽  
Jeff H. Lipton ◽  
Anna Dmoszynska ◽  
Raymond S. Wong ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Newly Diagnosed ◽  
Phase 3

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

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

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

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