A Retrospective Analysis of Pneumocystis Jirovecii Pneumonia Infection in Patients Receiving Idelalisib in Clinical Trials
Notice bibliographique
Résumé
Abstract Introduction: Opportunistic infections such as Pneumocystis jirovecii pneumonia (PJP) occur commonly in immunocompromised hosts such as patients (pts) with cancer (especially hematological malignancies such as chronic lymphocytic leukemia [CLL] and indolent non-Hodgkin lymphoma [iNHL]) or those receiving immunosuppressive therapies (such as steroids, chemotherapy). Recently, an increased risk of PJP infection was identified in 3 ongoing phase 3 studies evaluating idelalisib, administered in combination with the standard regimens rituximab (R) or bendamustine and rituximab (BR), in front-line CLL and early-line iNHL. Subsequently, a comprehensive analysis evaluating PJP infection across the clinical development program was performed to identify possible risk factors for developing PJP infection, including age, concomitant therapy (co-therapy) administered, geographic distribution of PJP infection, and regional use of prophylaxis. Methods: A retrospective analysis of 2198 pts receiving study treatment with idelalisib alone or in combination with co-therapy (anti-CD20 antibody or BR) and pts receiving only co-therapy (anti-CD20 ± bendamustine) (n = 1391 and 807, respectively) across 8 studies (frontline/relapsed CLL and relapsed iNHL) between 2010 and 2016 was performed. PJP infection was defined based on MedDRA high-level term of pneumocystis infections. In this analysis, other parameters were included for evaluation of risk of developing PJP infection-prophylaxis for PJP, geographic region, age, and CD4 count. Results: The overall incidence of PJP infection was 2.5% in pts on idelalisib ± co-therapy vs 0.2% in pts receiving only anti-CD20 antibody alone or BR alone (relative risk = 12.5). The median time to PJP event was 141 days since initiation of IDELA or co-therapy. The incidence of PJP infection was similar, irrespective of pt age. In the pt population receiving IDELA ± co-therapy - prophylaxis for PJP reduced the incidence of infection to 1.3% (from 3.4% in pts not receiving prophylaxis). Additionally, analysis by type of co-therapy received - the incidence of PJP infection was 2.2% vs 3.1% with IDELA + BR and IDELA + anti-CD20 alone respectively. A correlation between CD4 count (<200 cells/mcL) and an increased risk of PJP infection was not observed. Additional data are provided in Table 1. Conclusion: There is a small but increased risk of PJP infection during treatment with idelalisib within the clinical trial program. These data suggest that prophylaxis for PJP may reduce the risk of infection by as much as 60%. Administration of PJP prophylaxis is now recommended in all pts receiving treatment with idelalisib. Disclosures Sehn: roche/genentech: Consultancy, Honoraria; amgen: Consultancy, Honoraria; seattle genetics: Consultancy, Honoraria; abbvie: Consultancy, Honoraria; TG therapeutics: Consultancy, Honoraria; celgene: Consultancy, Honoraria; lundbeck: Consultancy, Honoraria; janssen: Consultancy, Honoraria. Hallek:Mundipharma: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Janssen-Cilag: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; F. Hoffmann-LaRoche: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau. Jurczak:Gilead Sciences: Research Funding; Celltrion, Inc: Research Funding; Janssen: Research Funding; Bayer: Research Funding; Acerta: Research Funding. Brown:Infinity: Consultancy; Gilead Sciences: Consultancy; Janssen: Consultancy; Pfizer: Consultancy; Sun BioPharma: Consultancy; Celgene: Consultancy; Roche/Genentech: Consultancy; Abbvie: Consultancy. Barr:Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; AbbVie: Consultancy. Catalano:Roche: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Gilead Sciences: Membership on an entity's Board of Directors or advisory committees. Coutre:Gilead Sciences: Consultancy, Research Funding. Furman:Gilead Sciences: Consultancy; Pharmacyclics: Consultancy, Speakers Bureau; Janssen: Consultancy; Genentech: Consultancy; Abbvie: Consultancy, Honoraria. Lamanna:Gilead Sciences: Membership on an entity's Board of Directors or advisory committees, Research Funding. Zelenetz:Gilead Sciences: Research Funding. Sharman:Gilead Sciences, Inc.: Honoraria, Research Funding. Adewoye:Gilead Sciences: Employment, Equity Ownership. Kim:Gilead Sciences: Employment, Equity Ownership. Flinn:Janssen: Research Funding; Pharmacyclics LLC, an AbbVie Company: Research Funding; Gilead Sciences: Research Funding; ARIAD: Research Funding; RainTree Oncology Services: Equity Ownership. Salles:Gilead: Honoraria, Research Funding; Novartis: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Roche/Genentech: Consultancy, Honoraria, Research Funding; Mundipharma: Honoraria; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria.
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 | 0,005 | 0,009 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,001 | 0,003 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,000 | 0,001 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 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 ».