scholarly journals Imatinib Mesylate Is Safe and Effective in Maintaining Cytogenetic and Molecular Response Achieved with 1 Year Nilotinib First Line in Newly Diagnosed Chronic Myeloid Leukemia: Preliminary Results of a Prospective Clinical Trial

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5445-5445
Author(s):  
Nour Moukalled ◽  
Radwan Massoud ◽  
Rami Mahfouz ◽  
Jean Elcheikh ◽  
Ali Bazarbachi
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Molecular Response ◽  
First Line ◽  
Metabolic Complications ◽  
Number Of Patients ◽  
Long Term Treatment

Abstract Background: Achieving complete cytogenetic response (CCyR) at 12 months for patients with chronic phase chronic myeloid leukemia (CML) treated with imatinib as first line, is associated with significantly improved progression-free survival. Nilotinib has shown a faster and higher rate of CCyR and molecular response as compared to imatinib. However, nilotinib use is associated with diet restriction, higher financial costs, and its long-term use is incriminated in cardiovascular and metabolic complications. Methods: In this prospective single center trial, we evaluated the ability of imatinib to maintain a CCyR achieved after 12 months of first-line treatment with nilotinib. Inclusion criteria were adult patients with previously untreated Philadelphia -positive CML in chronic phase, with a WHO performance status ≤ 2. Patients received 1-year treatment with nilotinib (300mg twice daily) then were shifted to imatinib 400mg daily. Results: Eleven patients (5 females) were so far enrolled in the study, with a median age at diagnosis of 50 years (range 31-83). Patients were started on Nilotinib at a median of 29 days (range 2-32) from diagnosis. One patient had to discontinue nilotinib after 6 months and start dasatinib due to recurrent pancreatitis that resolved upon interruption of nilotinib. Eight patients completed one year of nilotinib, and were switched to Imatinib. The remaining 2 patients are currently on nilotinib as per protocol (less than 12 months since inclusion). Three patients on imatinib had to be switched back to nilotinib, because of imatinib intolerance (n=2; elevated liver transaminases and myositis) or because of loss of MMR (n=1). Therefore, at last follow up (median 64 months), 5 patients are on imatinib, 5 on nilotinib and 1 on dasatinib. All patients (100%) achieved complete hematological response (CHR) and CCyR at 3 and 18 months respectively, and maintained them thereafter. At 12 months, 6 out of 8 eligible patients achieved complete molecular response (CMR; n=3) or major molecular response (MMR; n=3). At 36 months, all eligible patients (n=7) were either in CMR (n=2) or in MMR (n=5). All patients who reached 4 years (n=6), 5 years (n=5) or 6 years (n=3) of follow up remained in either MMR or CMR. No patient developed long-term serious adverse event including cardiovascular or metabolic complications. Conclusion: These findings suggest that imatinib can maintain MMR achieved on short-term nilotinib therapy. This strategy is a potentially safe and effective long-term treatment approach, minimizing costs and cardiovascular and metabolic complications. This however, needs confirmation with a larger number of patients. Table. Table. Disclosures No relevant conflicts of interest to declare.

Long Term Molecular Response To Triple Therapy With High Doses Imatinib In Patients With Chronic Myeloid Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5199-5199
Author(s):  
Jose Luis Lopez ◽  
Hector Joel Rico
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Adverse Events ◽  
Triple Therapy ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Hematological Toxicity ◽  
Molecular Response ◽  
Sokal Score

Abstract Introduction Imatinib 400 mg daily is considered the best initial therapy for patients with chronic myeloid leukemia (CML) in the chronic phase (CP). However, only minorities of patients have a complete molecular remission (CMR) Another agent has antileukemic activity against Bcr-Abl-positive cells like Ara-C and interferon, the association of this drugs and imatinib in CML was evaluated in several trials with an increase in molecular response. The aim of this study was to evaluate the major molecular response (MMR) at 12 months with triple treatment schedule, analyze the evolution of these patients and general and hematologic toxicity. Material and Methods Patients diagnosed with CML at the Hospital General de Zona #35 in Juarez, Mexico were included. Eligibility criteria were adults with diagnosis of CML chronic phase on triple regimen for at least 12 months: Pegylated interferon-α 2a 90mcgrs via subcutaneous / week for 4 weeks + PO imatinib 800 mgs a day for 30 days + 20 mgs/mt2 cytarabine from day 1 to 10 subcutaneus. Patients were stratified according to Sokal score at diagnosis. The molecular analysis was performed in Quest diagnostic laboratory by means of real-time quantitative polymerase-chain-reaction (RT-PCR) results are expressed as a percent ratio of BCR-ABL1 to ABL1 and further adjusted to the international scale (IS) since august 2012. Patients could have received previous treatment for CML, with the exception of bone marrow transplantation. All patients provided written informed consent. This study was conducted in accordance with the Declaration of Helsinki. Molecular and adverse events were assessed. An analysis of molecular response at 12 months was planned and follows up patients with MMR every year. A MMR was defined a Bcr-Abl 0.1% or less and complete molecular response (CMR) as undetectable. Hematological toxicity was assessed according WHO scale. Results 41 patients completed the first 12 months in therapy, with a mean age of 44.4 years (17 to 71) 51% male and 49% female, the median and ranges of hemoglobin levels, leukocyte and platelet counts at diagnosis were 10.2 g/dl (5.1-16.0), 209.000 μL3 (10,600 - 529.000) and 565.500 μL (130.000 to 4,272,000) respectively. The percentages of cases by Sokal risk group were 70.7% low, 24.4% intermediate and 4.9% high risk. The Median follow up time was 58 months (range 14 to 120). At 12 months the number of patients who were in MMR was 27 (65.9%) including 8 (19.5%) with no BCR-ABL detectable. Median duration of triple therapy exposure at first year was 24 Weeks (range 12 to 32) Responses by Sokal score were 62%, 70% and 100% for low, intermediate and high respectively. Adverse events occurred in 88% cases; 33% of patients has at least one adverse event (AE) 42% 2 EA and 28% 3 EA, the most important EA was gastrointestinal. (table 1) 43.9% of patients has Hematological toxicity III-IV Median follow up time of patients in RMM was 64 months (range16-120) 2 patients were no evaluable. Patients who have RMM at 12 months 50% achieve a CMR at last follow up, 33% continues in RMM and 17% loss molecular response. Patients with CMR 72% have undetectable bcr-abl, 14% have loss molecular response and 14% in MMR Conclusions In this group of patients MMR was achieved in a higher proportion of cases at 12 months of treatment which is important in the long-term prognosis. Side effects grade 3 and 4 hematologic and non-hematologic were significant in this series of cases appearing in 44 and 88% respectively, which requires close monitoring of patients. The combination of interferon α2a, cytarabine and high-dose imatinib induces a MMR of 66% at 12 months of treatment, a 28%, 56% and 16% in MMR, CMR and loss molecular response respectively at last follow up. Clinical files n =36 Disclosures: No relevant conflicts of interest to declare.

scholarly journals Budget Impact analysis of the first-line treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) adult patients

2017 ◽  
Vol 18 (1) ◽  
Author(s):  
Francesco Mennini ◽  
Andrea Marcellusi ◽  
Raffaella Viti ◽  
Giuseppe Saglio
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Myeloid Leukemia ◽  
Budget Impact ◽  
Kinase Inhibitor ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Molecular Response ◽  
First Line ◽  
Number Of Patients

Background: Tyrosine kinase inhibitors (TKI) have dramatically improved survival in chronic myeloid leukemia in chronic phase (CML‐CP), with a high percentage of patients reaching a major molecular response (MMR). Recently, several clinical trials demonstrated that some patients with CML-CP who achieve a sustained MMR on tyrosine kinase inhibitor (TKI) therapy can safely discontinue their therapy and attempt treatment-free remission (TFR).Objective: The aim of the study was to evaluate the clinical and economic impact of TFR in naïve patients with CML-CP who start treatment with nilotinib, imatinib or dasatinib as first-line therapy, from the perspective of the Italian National Health Service (NHS).Methods: An Excel-based budget impact model was developed, in order to estimate the costs of the patients in first-line pharmacological treatment with CML. A specific Markov model was built, to simulate seven years of treatment with different TKIs. A systematic literature review was carried out, to identify the epidemiological and economic data, which were subsequently used to inform the model. The model considers two scenarios: 1) a Standard of Care (SoC) scenario, with the current estimated distribution of patients over the various TKI treatment, versus 2) an innovative scenario, characterized by an increase in the use of nilotinib (+28%) and generic imatinib (+35%) and a decrease in the use of dasatinib (-17%). A one-way deterministic sensitivity analysis was performed, in order to consider the variability of the results as a function of the main parameters considered in the model.Results: The model estimated that 775 patients with CML-CP could be treated with a TKI as first-line drug. The innovative scenario could increase TFR patients by approximately 60% and reduce the costs by more than € 30 million over 7 years. The increase in the use of nilotinib and the generic imatinib would generate a significant expenditure reduction.Conclusions: This study demonstrates the economic effects of discontinuing TKIs in CML-CP patients. The increase in the use of nilotinib and the generic imatinib could generate an increase in the number of patients who achieve TFR, as well as an actual cost reduction.

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.

scholarly journals Estimating leukemia-free survival after allografting for chronic myeloid leukemia: a new method that takes into account patients who relapse and are restored to complete remission

Blood ◽  
2000 ◽  
Vol 96 (1) ◽  
pp. 86-90 ◽  
Author(s):  
Charles Craddock ◽  
Richard M. Szydlo ◽  
John P. Klein ◽  
Francesco Dazzi ◽  
Eduardo Olavarria ◽  
...  
Keyword(s):  
Stem Cell ◽  
Chronic Myeloid Leukemia ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
New Method ◽  
Free Survival ◽  
Number Of Patients ◽  
Unrelated Donors

Abstract A significant number of patients who relapse after allogeneic stem cell transplantation (SCT) for chronic myeloid leukemia (CML) will achieve sustained remissions after treatment with interferon-, second transplants, or donor lymphocyte infusions (DLI) from the original stem cell donor. Because leukemia-free survival (LFS) is at present defined as survival without evidence of relapse at any time posttransplant, patients who relapse but are then restored to complete remission are treated as failures when estimating LFS. We have established a new category of LFS, termed current LFS (CLFS), which we define as survival without evidence of leukemia at the time of most recent assessment. To gauge the contribution of treatment for relapse to the efficacy of allogeneic SCT in the management of CML in chronic phase, we compared conventional LFS and CLFS in 189 consecutive patients who underwent SCT over a 7-year period with a minimum follow-up of 3 years. Patients with sibling donors (n = 111) received cyclosporine and methotrexate as prophylaxis for graft versus host disease; patients with unrelated donors (n = 78) also received Campath-1G or 1H as intravenous T-cell depletion. The 5-year LFS defined conventionally was 36% (CI: 29% to 43%) versus a 5-year CLFS of 49% (CI: 36% to 62%). This new method of defining LFS confirms the view that appropriate “salvage” therapy, principally DLI, makes a major contribution to the capacity of allogeneic SCT to produce long-term LFS in patients who receive SCT for CML and emphasizes the importance of redefining LFS to take account of successful treatment of relapse.

scholarly journals A Retrospective Analysis about Frequency of Monitoring in Italian Chronic Myeloid Leukemia Patients after Discontinuation

2020 ◽  
Vol 9 (11) ◽  
pp. 3692
Author(s):  
Matteo Dragani ◽  
Giovanna Rege Cambrin ◽  
Paola Berchialla ◽  
Irene Dogliotti ◽  
Gianantonio Rosti ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Chronic Phase ◽  
Molecular Response ◽  
Molecular Monitoring ◽  
Delay In Diagnosis ◽  
Number Of Patients

Successful discontinuation of tyrosine kinase inhibitors has been achieved in patients with chronic-phase chronic myeloid leukemia (CML). Careful molecular monitoring after discontinuation warrants safe and prompt resumption of therapy. We retrospectively evaluated how molecular monitoring has been conducted in Italy in a cohort of patients who discontinued tyrosine kinase inhibitor (TKI) treatment per clinical practice. The outcome of these patients has recently been reported—281 chronic-phase CML patients were included in this subanalysis. Median follow-up since discontinuation was 2 years. Overall, 2203 analyses were performed, 17.9% in the first three months and 38.4% in the first six months. Eighty-six patients lost major molecular response (MMR) in a mean time of 5.7 months—65 pts (75.6%) during the first six months. We evaluated the number of patients who would experience a delay in diagnosis of MMR loss if a three-month monitoring schedule was adopted. In the first 6 months, 19 pts (29.2%) would have a one-month delay, 26 (40%) a 2-month delay. Very few patients would experience a delay in the following months. A less intense frequency of monitoring, particularly after the first 6 months off treatment, would not have affected the success of treatment-free remission (TFR) nor put patients at risk of progression.

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