scholarly journals A randomized controlled trial comparing peginterferon-α-2a versus observation after stopping tyrosine kinase inhibitor in chronic myeloid leukemia patients with deep molecular response for at least two years

2020 ◽  
Author(s):  
Jew Win Kuan ◽  
Kian Meng Chang ◽  
Chin Lee Phan ◽  
Shu Ping Wong ◽  
Soo Min Lim ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Controlled Trial ◽  
Molecular Response ◽  
Randomized Controlled ◽  
National Medical ◽  
Deep Molecular Response ◽  
Treatment Free Remission

Abstract BackgroundInterferon (IFN) is a logical possibility to increase treatment free remission (TFR) rate in chronic myeloid leukemia (CML). We conducted the first randomized controlled trial comparing the use of pegIFN versus observation in CML patients attempting TFR.MethodsAdult CML patients with stable deep molecular response for ≥ 2 years with ≥ 2 readings of MR4.5 were randomized into two arms -- subcutaneous pegIFN-α-2a starting at 180 µg weekly for a year, followed by observation, or observation.ResultsA total of 30 patients were recruited (pegIFN n = 15, observation n = 15). Median follow-up was 38.1 months (range 15.9–49.4) and 23.8 (1.5–51.0) in pegIFN and observation arm, respectively. A total of 11 patients relapsed (pegIFN n = 4, observation n = 7). The median time of relapse was 13.1 months (range 9.2 to 25.5) and 4.4 (1.2 to 13.6) in pegIFN and observation arm, respectively. Only 8 out of 15 (53%) patients completed 52 doses of pegIFN with mean dose of 43 out of 52 doses (range 20 to 52). Dose of tolerable pegIFN was age dependent.ConclusionPegIFN is a potential consolidative therapy to increase TFR.Trial registration:(1) Malaysia National Medical Research Register (NMRR): NMRR-13-1186-15491. Approved 23rd September 2014, https://www.nmrr.gov.my/fwbLoginPage.jsp(2) ClinicalTrials.gov: NCT02381379. Registered on 24th Feb 2015, https://clinicaltrials.gov/ct2/results?cond=&term=NCT02381379&cntry=&state=&city=&dist=

scholarly journals A randomized controlled trial comparing peginterferon-α-2a versus observation after stopping tyrosine kinase inhibitor in chronic myeloid leukemia patients with deep molecular response for at least two years

2020 ◽  
Author(s):  
Jew Win Kuan ◽  
Kian Meng Chang ◽  
Chin Lee Phan ◽  
Shu Ping Wong ◽  
Soo Min Lim ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Controlled Trial ◽  
Molecular Response ◽  
Randomized Controlled ◽  
National Medical ◽  
Deep Molecular Response ◽  
Treatment Free Remission

Abstract Background: Interferon (IFN) is a logical possibility to increase treatment free remission (TFR) rate in chronic myeloid leukemia (CML). We conducted the first randomized controlled trial comparing the use of pegIFN versus observation in CML patients attempting TFR. Methods: Adult CML patients with stable deep molecular response for ≥ 2 years with ≥2 readings of MR4.5 were randomized into two arms -- subcutaneous pegIFN-α-2a starting at 180µg weekly for a year, followed by observation, or observation. Results: A total of 30 patients were recruited (pegIFN n=15, observation n=15). Median follow-up was 38.1 months (range 15.9-49.4) and 23.8 (1.5-51.0) in pegIFN and observation arm, respectively. A total of 11 patients relapsed (pegIFN n=4, observation n=7). The median time of relapse was 13.1 months (range 9.2 to 25.5) and 4.4 (1.2 to 13.6) in pegIFN and observation arm, respectively. Only 8 out of 15 (53%) patients completed 52 doses of pegIFN with mean dose of 43 out of 52 doses (range 20 to 52). Dose of tolerable pegIFN was age dependent. Conclusion: PegIFN is a potential consolidative therapy to increase TFR. Trial registration:(1) Malaysia National Medical Research Register (NMRR): NMRR-13-1186-15491. Approved 23rd September 2014, https://www.nmrr.gov.my/fwbLoginPage.jsp(2) ClinicalTrials.gov: NCT02381379. Registered on 24th Feb 2015, https://clinicaltrials.gov/ct2/results?cond=&term=NCT02381379&cntry=&state=&city=&dist=

scholarly journals Why is it critical to achieve a deep molecular response in chronic myeloid leukemia?

Haematologica ◽  
2020 ◽  
Vol 105 (12) ◽  
pp. 2730-2737
Author(s):  
Susan Branford
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Outcome Measurement ◽  
Quantitative Polymerase Chain Reaction ◽  
Response To Therapy ◽  
Molecular Response ◽  
Deep Molecular Response ◽  
Treatment Free Remission ◽  
Tki Discontinuation

The primary goal of tyrosine kinase inhibitor (TKI) therapy for patients with chronic myeloid leukemia is survival, which is achieved by the vast majority of patients. The initial response to therapy provides a sensitive measure of future clinical outcome. Measurement of BCR-ABL1 transcript levels using real-time quantitative polymerase chain reaction standardized to the international reporting scale is now the principal recommended monitoring strategy. The method is used to assess early milestone responses and provides a guide for therapeutic intervention. When patients successfully traverse the critical first 12 months of TKI therapy, most will head towards another milestone response, deep molecular response (DMR, BCR-ABL1 ≤0.01%). DMR is essential for patients aiming to achieve treatment-free remission and a prerequisite for a trial of TKI discontinuation. The success of discontinuation trials has led to new treatment strategies in order for more patients to reach this milestone response. DMR has been incorporated into endpoints of clinical trials and is considered by some expert groups as the optimal treatment response. But is DMR a stable response and does it provide the ultimate protection against TKI resistance and death? Do we need to increase the sensitivity of detection of BCR-ABL1 to better identify the patients who would likely remain in treatment-free remission after TKI discontinuation? Is it necessary to switch current TKI therapy to a more potent inhibitor if the goal is to achieve DMR? These are issues that I will explore in this review.

Fatigue Perpetuating Factors as Mediators of Change in a Cognitive Behavioral Intervention for Targeted Therapy-Related Fatigue in Chronic Myeloid Leukemia: A Pilot Study

2021 ◽  
Author(s):  
Kelly A Hyland ◽  
Ashley M Nelson ◽  
Sarah L Eisel ◽  
Aasha I Hoogland ◽  
Javier Ibarz-Pinilla ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Targeted Therapy ◽  
Chronic Myeloid Leukemia ◽  
Self Efficacy ◽  
Myeloid Leukemia ◽  
Controlled Trial ◽  
Activity Patterns ◽  
Self Report ◽  
Cognitive Behavioral ◽  
Randomized Controlled

Abstract Background Cognitive behavioral therapy for targeted-therapy related fatigue (CBT-TTF) has demonstrated preliminary efficacy in reducing fatigue in patients treated with tyrosine kinase inhibitors (TKIs) for chronic myeloid leukemia (CML). Purpose The aim of the current analyses was to explore whether fatigue perpetuating factors (disturbed sleep/wake cycle, dysregulated activity patterns, maladaptive cognitions about fatigue and cancer, insufficient processing of cancer and treatment, inadequate social support and interactions, heightened fear of cancer progression) changed over time in patients receiving CBT-TTF, and whether the effect of CBT-TTF on fatigue was mediated by these factors. Methods Secondary data analyses were conducted from a pilot randomized controlled trial. Patients with CML treated with a TKI who reported moderate to severe fatigue were randomized 2:1 to CBT-TTF delivered via FaceTime for iPad or a waitlist control condition (WLC). Self-report measures of fatigue and fatigue perpetuating factors were obtained before randomization and post-intervention (i.e., approximately 18 weeks later). Mixed model and mediation analyses using bootstrap methods were used. Results A total of 36 participants (CBT-TTF n = 22, WLC n = 14) who had baseline and 18-week follow-up data and attended >5 sessions for CBT-TTF were included. Participants randomized to CBT-TTF reported improvements in activity (mental, physical, social, p’s ≤ .023) and cognitions (helplessness, catastrophizing, focusing on symptoms, self-efficacy, p’s ≤ .003) compared to WLC. Mental activity, social activity, self-efficacy, helplessness, and focusing on symptoms, as well as sleep and insufficient processing (avoidance) mediated the relationship between treatment group and fatigue. Conclusions CBT-TTF appears to improve TKI-related fatigue in CML patients through changes in behavior (sleep, activity patterns) and cognitions about fatigue and cancer. A larger randomized controlled trial is warranted to confirm these findings.

scholarly journals Current Strategies and Future Directions to Achieve Deep Molecular Response and Treatment-Free Remission in Chronic Myeloid Leukemia

2020 ◽  
Vol 10 ◽  
Author(s):  
Mario Annunziata ◽  
Massimiliano Bonifacio ◽  
Massimo Breccia ◽  
Fausto Castagnetti ◽  
Antonella Gozzini ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Molecular Response ◽  
Future Directions ◽  
Deep Molecular Response ◽  
Treatment Free Remission

scholarly journals Impact of BCR-ABL1 Transcript Type on Response, Treatment-Free Remission Rate and Survival in Chronic Myeloid Leukemia Patients Treated with Imatinib

2021 ◽  
Vol 10 (14) ◽  
pp. 3146
Author(s):  
Sílvia Marcé ◽  
Blanca Xicoy ◽  
Olga García ◽  
Marta Cabezón ◽  
Natalia Estrada ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Positive Impact ◽  
Remission Rate ◽  
Progression Rate ◽  
Molecular Response ◽  
Treatment Free Remission ◽  
Transcript Type

The most frequent BCR-ABL1-p210 transcripts in chronic myeloid leukemia (CML) are e14a2 and e13a2. Imatinib (IM) is the most common first-line tyrosine–kinase inhibitor (TKI) used to treat CML. Some studies suggest that BCR-ABL1 transcript types confer different responses to IM. The objective of this study was to correlate the expression of e14a2 or e13a2 to clinical characteristics, cumulative cytogenetic and molecular responses to IM, acquisition of deep molecular response (DMR) and its duration (sDMR), progression rate (CIP), overall survival (OS), and treatment-free remission (TFR) rate. We studied 202 CML patients, 76 expressing the e13a2 and 126 the e14a2, and correlated the differential transcript expression with the above-mentioned parameters. There were no differences in the cumulative incidence of cytogenetic responses nor in the acquisition of DMR and sDMR between the two groups, but the e14a2 transcript had a positive impact on molecular response during the first 6 months, whereas the e13a2 was associated with improved long-term OS. No correlation was observed between the transcript type and TFR rate.

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