Long-Term Evaluation of Luspatercept in Erythropoiesis-Stimulating Agent (ESA)-Intolerant/Refractory Patients (pts) with Lower-Risk Myelodysplastic Syndromes (LR-MDS) in the Phase 3 MEDALIST Study
Notice bibliographique
Résumé
Background: Pts with LR-MDS receiving luspatercept in the phase 3 MEDALIST trial previously reported durable, long-term red blood cell (RBC) transfusion independence (RBC-TI) (Fenaux P, et al. J Clin Oncol 2022;40[suppl 16]. Abstract 7056). MEDALIST pts were eligible to enroll in a follow-up study to evaluate long-term efficacy and safety. Aims: To report long-term efficacy and safety outcomes in ESA-refractory/intolerant pts with LR-MDS treated with luspatercept in the MEDALIST trial with an additional 26 mo of follow-up from the final MEDALIST data cutoff. Methods: Eligible pts were ≥ 18 y of age; IPSS-R-defined Very low-, Low-, or Intermediate-risk MDS with ring sideroblasts; were refractory, intolerant, or unlikely to respond to ESAs, and required regular RBC transfusions. Pts were randomized 2:1 to luspatercept (starting dose 1.0 mg/kg, with titration up to 1.75 mg/kg) or placebo. Efficacy outcomes include RBC-TI ≥ 8 wk and ≥ 16 wk. Cumulative duration of response was determined by Kaplan-Meier (KM) analysis. Rates of longest single and cumulative duration of RBC-TI ≥ 1 y and exposure-adjusted incidence rates (EAIR) of treatment-emergent adverse events (TEAEs) and AEs of special interest (AESIs) were calculated. Rates of high-risk (HR)-MDS and acute myeloid leukemia (AML) progression were calculated from LR-MDS diagnosis to HR-MDS/AML diagnosis, or to last HR-MDS/AML follow-up date for pts who did not progress. Results: As of January 2, 2023, 11 pts remained on luspatercept treatment; 8 pts randomized to luspatercept and none from placebo continued in post-treatment follow-up. The median (range) follow-up time was 39.9 (2.8-76.0) mo for luspatercept arm pts and 38.7 (1.7-68.6) mo for placebo arm pts. The median (range) duration of treatment was 50.9 (5.9-332.9) wk for luspatercept pts and 24.0 (9.0-103.0) wk for placebo pts. Seventy-five of 153 (49.0%) luspatercept pts achieved RBC-TI ≥ 8 wk during the entire treatment period and 53/75 (70.7%) had ≥ 2 response periods with a median cumulative duration of 110.14 wk (95% confidence interval [CI], 53.71-154.14; Figure A). Overall, 31/75 (41.3%) luspatercept pts had the longest RBC-TI duration ≥ 1 y, and 44/75 (58.7%) had a cumulative RBC-TI duration ≥ 1 y. In total, of the 48/153 (31.4%) pts receiving luspatercept who achieved RBC-TI ≥ 16 wk during the entire treatment period, 32/48 (66.7%) had ≥ 2 response periods with a median cumulative duration of 129.29 wk (95% CI, 79.86-240.43). Grade 3/4 treatment-related TEAEs were reported in 14/153 (9.2%; EAIR, 5.3 per 100 pt-y [PYs]) and 3/76 (3.9%; EAIR, 6.6 per 100 PYs) luspatercept and placebo pts, respectively; TEAEs of any grade leading to permanent treatment discontinuation were reported in 24/153 (15.7%; EAIR, 8.6 per 100 PYs) luspatercept and 6/76 placebo pts (7.9%; EAIR, 13.0 per 100 PYs). The most common TEAEs of any grade reported in > 5% of luspatercept pts were fatigue (47/153 [30.7%]; EAIR, 22.1 per 100 PYs; vs placebo, 11/76 [14.5%]; EAIR, 27.1 per 100 PYs), diarrhea (47/153 [30.7%]; EAIR, 23.5 per 100 PYs; vs placebo, 8/76 [10.5%]; EAIR, 18.4 per 100 PYs), asthenia (41/153 [26.8%]; EAIR, 18.8 per 100 PYs; vs placebo, 9/76 [11.8%]; EAIR, 21.5 per 100 PYs), peripheral edema (40/153 [26.1%], EAIR, 17.6 per 100 PYs; vs placebo, 13/76 [17.1%]; EAIR, 32.0 per 100 PYs), and back pain (38/154 [24.7%]; EAIR, 16.8 per 100 PYs; vs placebo, 5/76 [6.6%]; EAIR, 11.7 per 100 PYs; Figure B). During the entire treatment period, 26/44 (59.1%), 9/23 (39.1%), and 12/86 (14.0%) pts who received ≤ 1 mg/kg, 1.33 mg/kg, and 1.75 mg/kg luspatercept, respectively, reported fatigue of any grade. No new progression to HR-MDS or AML events have been reported since the last data cutoff (Santini V et al. Blood 2022;140[suppl 1]:4079-4081). Conclusions: Pts with LR-MDS who received luspatercept for > 2 years longer than in the original MEDALIST study, continued to experience sustained periods of RBC-TI with more than half of pts experiencing cumulative RBC-TI for ≥ 1 year. The long-term safety profile of luspatercept is consistent with previous shorter-term reports, and AEs were mostly lower grade with rates of fatigue decreasing with increasing luspatercept dose. These data demonstrate the long-term efficacy and safety of luspatercept in pts with LR-MDS intolerant/ineligible for ESA treatment.
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 machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,002 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,001 |
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 source (Gemma direct ou Codex distillé), 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 ».