PS1162 COMBINATION THERAPY TO PREVENT IBRUTINIB WITHDRAWAL: CONTINUED IBRUTINIB WITH THE ADDITION OF VENETOCLAX AT TIME OF PROGRESSION IN IBRUTINIB‐TREATED PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)
Notice bibliographique
Résumé
Background: We have previously reported that ∼50% of CLL patients (pts) experience rapid flare of disease when they discontinue ibrutinib therapy due to progression of disease (CLL or Richter's transformation [RT]) (Hampel et al, JCO suppl, 2018). This lead to the clinical practice of overlapping venetoclax with ibrutinib for combination therapy in this setting to prevent ibrutinib withdrawal. Aims: To evaluate the role of continuing ibrutinib beyond the start of salvage venetoclax in pts who have progression of disease on ibrutinib monotherapy, both in preventing ibrutinib withdrawal associated with ibrutinib discontinuation and in disease response. Methods: We identified all CLL pts at Mayo Clinic (3/2017–11/2018) who had disease progression on ibrutinib therapy, where venetoclax was added as subsequent treatment while ibrutinib was continued. CLL‐specific characteristics, treatment timeline and toxicities, and disease course following combination therapy were ascertained. All pts started venetoclax according to the weekly ramp‐up per the package instructions. Results: Eighteen pts treated with the addition of venetoclax to ibrutinib therapy were identified; indications were CLL progression (n = 13) and RT (n = 5). BTK or PLCG2 mutations were present in 8/13 pts. Median duration of follow‐up was 9.6 months after the start of combination therapy. The target venetoclax dose was reached by 5 weeks in 13 pts; reasons for delaying or stopping dose escalation included diarrhea (n = 2), sepsis (n = 2), and neutropenia (n = 1). No patient experienced a disease flare during venetoclax ramp‐up. The median duration of combination ibrutinib and venetoclax therapy was 3 months (range, 0–14 months). Of 18 pts who started combination therapy with ibrutinib and venetoclax, ibrutinib was discontinued in 10 pts. Reasons included hematopoietic stem cell transplant (n = 2), planned stop after adequate disease control (n = 4), financial reasons (n = 1), toxicity (neutropenia n = 1, immune thrombocytopenia/bleeding risk n = 1), and death (n = 1). Only 1 patient experienced ibrutinib withdrawal, which occurred following planned discontinuation after clinical complete response (CR) with a 41 day overlap and toleration of venetoclax 400 mg daily; management with re‐initiation of ibrutinib was effective in regaining disease control. Of 9 pts who stopped ibrutinib, 4 pts had a slow taper over 2–8 weeks, and 2 pts also received corticosteroids at the time of ibrutinib discontinuation. Among the other 8 pts who did not discontinue ibrutinib, 6 pts remain on the combination with venetoclax (median duration 6.5 months, range 3–14 months), and 2 pts continued on ibrutinib following venetoclax discontinuation due to disease progression (both pts received further combination of ibrutinib with multi‐agent chemotherapy). The overall response rate (ORR) to combination therapy with ibrutinib and venetoclax was 81% (CR/clinical CR n = 9, partial response n = 4, stable disease n = 1, and primary refractory disease n = 2). The duration of combination therapy was <4 weeks in 2 pts, precluding response assessment. The estimated 12‐month event‐free survival was 54% (95% CI 33–87%), and the estimated 12‐month overall survival from start of combination therapy was 79% (95% CI 60–100%); see Figure 1. Summary/Conclusion: Among CLL pts who develop progression of disease on ibrutinib monotherapy, continued ibrutinib therapy with addition of venetoclax was feasible, ameliorated ibrutinib withdrawal, and was associated with high ORR. image
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 | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| 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) | 0,002 | 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 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 ».