S248: SIERRA TRIAL RESULTS WITH A TARGETED RADIOTHERAPY, IOMAB-B, A MYELOABLATIVE CONDITIONING WITH REDUCED INTENSITY TOLERABILITY YIELDS HIGH CR, LONG TERM SURVIVAL IN HSCT INELIGIBLE ACTIVE R/R AML
Notice bibliographique
Résumé
Background: Despite recent advances in the treatment of acute myeloid leukemia (AML), prognosis for patients with relapsed, refractory (R/R) disease remains poor. The only potentially curative option for these patients is allogeneic hematopoietic stem cell transplantation (HSCT). However, only a minority reach complete remission (CR) or sufficient disease control to allow for HSCT, and moreover induction and conditioning regimens are poorly tolerated in the older population. Iomab-B (131I-apamistamab) is an anti-CD45 radioimmunoconjugate delivering targeted myeloablative radioactivity to stem cells and leukemic blasts with reduced intensity tolerability. Aims: SIERRA (NCT02665065) is a multi-centre, randomized, controlled phase 3 study comparing the efficacy of Iomab-B based conditioning versus physician’s choice of conventional care (CC) in older, R/R AML with active disease routinely ineligible for HSCT. Primary endpoint was durable CR (dCR), defined as CR ≥6 mos with or without platelet recovery (CRp). Methods: Pts ≥55 years of age with active R/R AML were randomized (1:1) to CC or Iomab-B with fludarabine and total body irradiation (2 Gy) followed by HSCT. CC pts achieving CR received physician’s choice conditioning and HSCT. Pts not achieving CR could crossover (CO) to Iomab-B-based conditioning followed by HSCT. Assessment for CR/CRp occurred between days 28-56 post HSCT or initiation of therapy on the CC arm. Pts in CR/CRp were evaluated for the primary endpoint of dCR 6 mos after achieving initial CR/CRp. Results: Baseline pt characteristics were balanced between both arms. 61% pts failed targeted therapies prior to enrolment, of whom 66% received venetoclax-based therapy. Median time to HSCT was 29 and 66.5 days on Iomab-B and CC arms (CC pts who had CR/CRp), respectively. The median infused activity of Iomab-B was 664.4 and 613.3 mCi in Iomab-B and CO arms respectively with median dose to marrow of 16 Gy in both arms. All pts who received the therapeutic dose of Iomab-B (n=66) underwent HSCT vs 14 (18.2%) on CC arm. Of evaluable pts (Iomab: 59; CC: 64), 44 (74.6%) pts on the Iomab-B arm achieved initial CR/CRp compared to 4 (6.3%) on CC. Durable CR rates were 22% vs 0% (95% CI; 12.29, 34.73; p<0.0001). The median overall survival (OS) was 6.4 vs 3.2 mos for pts receiving Iomab-B-based conditioning followed by HSCT vs non-CO pts on CC arm, respectively. Median OS in the CO vs non-CO cohorts on the CC arm was 7.1 vs 3.2 mos (HR=0.51; 95% CI [0.31, 0.85]; p=0.0078). OS in pts receiving Iomab-B and HSCT achieving dCR (n=13) was 92% and 60% at 1 and 2 yrs respectively (Figure 1). Event-free survival (EFS) at 6 mos on Iomab-B vs CC was 26% vs 0.2% (HR=0.22; 95% CI [0.15, 0.34]; p<0.0001). Iomab-B-based conditioning followed by HSCT was well tolerated with a favourable safety profile, with lower rates of sepsis in pts receiving Iomab-B based conditioning vs pts undergoing standard of care HSCT.Summary/Conclusion: In pts ≥55 yrs with active R/R AML, Iomab-B was able to safely deliver myeloablative doses of targeted radiation to bone marrow. Iomab-B based conditioning with HSCT resulted in rapid engraftment and high initial CR/CRp rates, a favourable toxicity profile and resulted in statistically significant improvement in the pre-specified primary endpoint of dCR. The majority of pts who achieved dCR are long term survivors, in whom OS and EFS was significant. Iomab-B based conditioning was well-tolerated and provided access to HSCT with curative potential in a vulnerable pt population traditionally not considered eligible for HSCT. Keywords: Radioimmunotherapy, Acute myeloid leukemia, Conditioning, Allogeneic hematopoietic stem cell transplant
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 | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,002 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,009 | 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 ».