Treatment‐Free Remissions in Children With Chronic Myeloid Leukemia (CML): A Prospective Study From the Tata Memorial Hospital (TMH) Pediatric CML (pCML) Cohort

Article

Author: Jain, Hemani ; Agiwale, Jayesh ; Shetty, Dhanlaxmi ; Rane, Pallavi ; Srinivasan, Shyam ; Patkar, Nikhil ; Roy Moulik, Nirmalya ; Subramanian, Papagudi G. ; Dhamne, Chetan ; Tembhare, Prashant ; Mohanty, Purvi ; Narula, Gaurav ; Banavali, Shripad ; Chatterjee, Gaurav ; Rajpal, Sweta ; Chichra, Akanksha ; Keerthivasagam, Swaminathan

ABSTRACTPediatric chronic myeloid leukemia (pCML) is a rare childhood malignancy, representing 2%–3% of all childhood leukemia. Tyrosine kinase inhibitors (TKIs) have greatly improved survival but pose challenges due to their long‐term effects on growth and bone health in children. We prospectively studied treatment‐free remission (TFR) in 45 children with pCML in chronic phase on imatinib. Eligibility criteria were as per current NCCN guidelines, with a less stringent qPCR monitoring scheduled every 3 months. TFR was successful in 71.1% (32 out of 45) of patients after a median follow‐up of 25 (range: 6–42) months. The TFR rates at 12 and 24 months were 70% and 66%, respectively. Children under 5 years had a TFR rate of 88.9%, compared to 61.8% in those over 5 years (p = 0.18). Eleven of the 13 patients who lost MMR did so within 6 months of discontinuation. The cumulative incidence of loss in MMR at 6, 12, and 24 months was 26.4%, 27%, and 33%, respectively. Ten out of 13 (76.9%) patients with discontinuation failure (DF) regained MMR within 3 (2–20) months of restarting imatinib. A significant correlation was found between higher T‐regulatory cell levels at baseline and DF (p = 0.005). More than half patients showed improved bone mineral density after 2 years of TFR. Our findings suggest that high TFR rates can be attained in pCML, with added benefits for bone health. Less frequent molecular monitoring was not associated with adverse outcomes and there seems to be a role of the immune system in sustaining TFR. The study is registered in the Clinical Trials Registry‐India (CTRI/2020/11/029199).

01 Jan 2025·Cancer

Outcomes of pregnancy in patients with chronic myeloid leukemia in the era of tyrosine kinase inhibitors

Article

Author: Matsumura, Itaru ; Kondo, Takeshi ; Kimura, Shinya ; Yoshida, Chikashi ; Watanabe, Naoki ; Okada, Masaya ; Takahashi, Naoto ; Murai, Kazunori ; Matsuki, Eri ; Takaku, Tomoiku ; Kodama, Takashi

AbstractBackgroundYoung female patients with chronic myeloid leukemia (CML) often face challenges becoming pregnant due to the teratogenicity of tyrosine kinase inhibitors (TKIs).MethodsThe authors conducted a nationwide survey of female patients with CML who experienced pregnancy between 2002 and 2020.ResultsInformation for 70 pregnancies in 49 patients was obtained. There were three types of pregnancies: CML onset during pregnancy (n = 9), unplanned pregnancy mostly during treatment with a TKI (n = 25), and planned pregnancy during treatment‐free remission (TFR) or treatment with interferon‐alpha (IFN‐α) (n = 36). The median duration from CML diagnosis to pregnancy in patients with planned pregnancy was significantly longer than that in patients with unplanned pregnancy (10.6 years vs. 4.1 years, p < .001). In 48 pregnancies that resulted in childbirth, TFR and treatment with IFN‐α were chosen in 26 and 17 pregnancies, respectively. Sustained major or deeper molecular response was observed in 18 of 26 pregnancies with TFR. The patients who fulfilled the requirements for TKI therapy discontinuation by European LeukemiaNet recommendations achieved a TFR rate of 77% in pregnancy. Treatment with IFN‐α might be effective for patients who are in complete cytogenetic response or deeper response (response rate, 76%).ConclusionPregnancy by TFR or treatment with IFN‐α could be a safe and feasible way for patients with CML. However, a substantial duration of treatment with a TKI before conception may be needed for planned pregnancy. Planning and evaluation for pregnancy should be considered at the time of CML onset for female patients with childbearing potential.

01 Dec 2024·Value in Health

The Cost-Effectiveness of Frontline Tyrosine Kinase Inhibitors for Patients With Chronic Myeloid Leukemia: In Pursuit of Treatment-Free Remission and Dose Reduction

Article

Author: Blijlevens, Nicole M A ; Ector, Geneviève I C G ; Metsemakers, Sanne J J P M ; Govers, Tim M ; Hermens, Rosella P M G

OBJECTIVESThe management of chronic myeloid leukemia (CML) now includes dose reduction (DR) and treatment-free remission (TFR). Evaluating the cost-effectiveness of lifelong-prescribed expensive tyrosine kinase inhibitors (TKIs) for CML is crucial. Prior cost-effectiveness evaluations state that imatinib is the favorable frontline TKI. Some of these evaluations address TFR, but not DR, nor aging and second-generation (2G)-TKIs upcoming patent expirations. This study evaluates the cost-effectiveness of frontline TKIs for CML patients including these factors.METHODSThis Markov model evaluates the cost-effectiveness of frontline TKIs for newly diagnosed patients with CML using 17 health states. Transition probabilities, costs, and utilities were derived from literature data. Incremental cost-effectiveness ratios were calculated. Sensitivity analysis and model validation were conducted.RESULTSNilotinib is most effective (20.13 quality-adjusted life-years [QALYs]) and imatinib is least effective (17.25 QALYs) for the model including TFR and DR. Imatinib was favored over dasatinib (89.80%), nilotinib (62.70%), and bosutinib (78.40%), at a willingness-to-pay threshold of €80 000 per QALY. Without TFR and DR, fewer QALYs were generated. For patients at the age of 70 years, imatinib has a high probability of being more cost-effective than dasatinib, nilotinib, and bosutinib. With 50% 2GTKI cost reductions, nilotinib is considered more cost-effective compared with imatinib (98.40%), dasatinib (94.80%), and bosutinib (68.90%).CONCLUSIONSThe findings indicate that 2GTKIs are more effective in generating QALYs, including for older (age >70 years) patients. Given the current TKI prices, imatinib remains cost-effective. Including DR and TFR in CML management generates more QALYs. Cost reductions from expected 2GTKIs patent expirations will greatly increase their cost-effectiveness. Results may inform 2GTKIs cost discussions after patent expiration, potentially broadening global availability. The findings also emphasize the importance of aiming for TFR and DR in CML management.

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Indication	Highest Phase	Country/Location	Organization	Date
Central Nervous System Diseases	Preclinical	US	Eli Lilly & Co.	22 Feb 2024

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