P667: RISK OF PROGRESSION IN CHRONIC PHASE-CHRONIC MYELOID LEUKEMIA PATIENTS ELIGIBLE FOR TYROSINE KINASE INHIBITOR DISCONTINUATION: FINAL ANALYSIS OF THE TFR-PRO STUDY
Notice bibliographique
Résumé
Background: Treatment discontinuation (TD) in patients (pts) with chronic phase (CP)-Chronic Myeloid Leukemia (CML) is recognized as one goal in the management of the disease. TD is generally safe, since MMR is achieved in almost all cases when TKI resumption is required. Disease progression (DP) to accelerated or blast phase (AP/BP) after TD was considered virtually impossible. However, recent reports documented at least 12 such cases, some of which fatal, raising safety concerns about TD. Aims: A quantification of the risk of DP in the setting of TFR has never been evaluated. The TFR-PRO study was designed to obtain a numerical assessment of the risk of DP in pts in deep molecular response (DMR) eligible for TD, regardless of their decision to attempt TD. Methods: This retro-prospective observational study enrolled CP-CML pts, followed at 20 centers in Italy, Canada, Germany, Spain, France. Pts eligibility included ≥4 years of TKI treatment and ≥18 months of stable DMR. The primary objective was to assess the risk of DP expressed as time adjusted rate (TAR) and its relationship to TD in CML pts who underwent TD. Pts eligible to TD who did not discontinue constituted the reference cohort. A flexible statistical approach allowed to attribute pts to the two groups according to their situation about TD (TD yes or no). Events developing in pts after the end of TD were considered associated to TD if they developed within 36 months since the end of TD. One secondary endpoint was the TAR of molecular relapse (MR, i.e. loss of MMR). Results: From July 24th, 2020 to November 10th, 2022, 907 pts were registered, of whom 870 were evaluable for the analysis (5152 person years). Median follow up was 5.5 years (IQR 2.6-8.6), median age at diagnosis was 50 years (IQR 40-61). Sokal score was low in 46.3%, intermediate in 34.8% and high in 18.9%. 505 pts (58%) attempted TD, 365 (42%) did not. MR occurred in 172/505 (34.1%) pts after TD, for a TAR of 11.8/100 person years (95% confidence interval (CI) [10.1-13.7]), but also in 64/365 (17.5%) pts of the reference cohort, for a TAR of 2.3/100 person years (95%CI [1.8-3.0]), p<0.0001. A representation of the estimated proportion of pts with MR is provided in the figure. Only one pt experienced DP to lymphoid BP, 55 after the end of TFR; he received BMT and is presently in remission. This event developed more than 36 months after MR, which was the protocol limit for considering an event linked to TD. Therefore, at the time of DP this pt was contributing to the reference cohort. Thus, the risk of DP was 1/870 or 0.1% (95% CI [0.0-0.6]) in the overall cohort, ranging from 0/505 or 0%, (95% CI 0.0-0.6%]) in the discontinuation cohort to 1/365 or 0.3% (95% CI [0.0-1.5%]) in the reference cohort. The TAR of DP was 0.019/100 person years (95%CI [0.003-0.138]) in the overall cohort, ranging from 0.0 (95%CI [0-0.002]) in the discontinuation cohort to 0.030 (95%CI [0.004-0.215]) in the reference cohort. The difference of this risk between the two cohorts is not statistically significant. Summary/Conclusion: These results indicate that pts who attempt TD have a significantly higher risk of MR than pts who do not. DP in pts eligible for TD is a rare event (approximately 1 in 1000 pts, or 0.019% per year in a single pt) and its relationship with TD is not demonstrated. It is important to underline that the pt experiencing DP had a very poor compliance to retreatment after the end of TFR, which contributed to the transformation of his CML. Therefore, when selecting pts for a TD attempt, emphasis should we given also to their willingness to resume TKI treatment in case of TD failure.Keywords: Blast crisis, Chronic myeloid leukemia, Progression, treatment-free remission
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,003 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».