Demographics, Baseline Characteristics, and Disease Symptom Burden in RESPONSE-2: A Randomized, Phase 3 Study of Ruxolitinib in Polycythemia Vera Patients (pts) Who Are Resistant to or Intolerant of Hydroxyurea (HU)
Notice bibliographique
Résumé
Abstract BACKGROUND: Polycythemia vera (PV) is characterized by increased red cell mass often associated with elevated leukocyte and platelet counts, splenomegaly and significant symptom burden. In the RESPONSE study, which only enrolled PV patients with splenomegaly, ruxolitinib (Rux) demonstrated superior improvements in hematocrit (HCT) control and reductions in spleen volume compared with best available therapy (BAT) in pts who were resistant to or intolerant of HU. Supportive data included clinically meaningful improvements in PV-related symptom burden and quality of life (QOL) measures. Here, we describe the baseline (BL) characteristics and symptom burden of PV pts resistant to or intolerant of HU enrolled in the RESPONSE-2 study, which unlike RESPONSE, enrolled PV patients with a nonpalpable spleen. METHODS: RESPONSE-2 is an open-label, randomized (1:1), multicenter, phase 3 study evaluating the efficacy and safety of Rux vs BAT in PV pts who are HU-resistant/-intolerant, require phlebotomy (PBT), and have no palpable spleen. Pts' BL symptom burden, BL QOL and BL pt-reported outcomes (PRO) were assessed by using 10-items modified Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS), the Pruritus Symptom Impact Scale (PSIS), European QOL Questionnaire (EQ-5D-5L), and Work Productivity and Activity Impairment: Polycythemia Vera V2.0 (WPAI: PV). RESULTS: A total of 149 pts were enrolled. BL demographic data from both arms combined are summarized in the Table. Forty percent of the patients were resistant whereas 60% were intolerant of HU treatment. Other than HU, prior treatments included interferons (15.4%), alkylating agents (8.1%), alkyl sulfonates (2.7%), pyrimidine analogs (0.7%), and other antineoplastic agents (1.0%). Ninety-seven percent of pts had at least 1 PBT within 16 weeks (wks) prior to screening and 72% had ≥ 2 PBT within 24 wks prior to screening. Past medical histories included hypertension (49%), pruritus (23%) and fatigue (9%). BL demographics of pts in RESPONSE-2 were generally comparable with previous PV studies (Table). Despite using frequent phlebotomy and cytoreductive agents during the screening period prior to randomization, 55% and 52% of pts had WBC counts greater than 10 × 109/L and platelet counts greater than 400 × 109/L, respectively, suggesting inadequately controlled disease even while receiving therapy. Additionally, pts had significant symptom burden at BL as measured by the MPN-SAF with fatigue (3.6) and pruritus (3.4) (Table). As measured by EQ-5D-5L scale, 26% and 19% of pts reported moderate to extreme pain/discomfort and depression, respectively. In WPAI outcomes, 40 of 149 pts reported missing work due to PV accounting for 14.3% of their working time. SUMMARY/CONCLUSION: Demographic and BL data from the RESPONSE-2 study highlight the significant unmet medical need in this inadequately controlled HU-resistant/-intolerant PV population. As expected, pts in RESPONSE-2 reported lower scores for symptoms associated with splenomegaly (early satiety, 1.8 vs 2.0; abdominal discomfort, 1.7 vs 2.0) as compared with RESPONSE population. In comparison to PV pts with splenomegaly in the RESPONSE trial, pts without splenomegaly in the RESPONSE-2 trial have a distinct but comparable disease burden with marked fatigue and pruritus. Table 1. Baseline demographics and symptoms (n = 149) Age, median (range), years 66.0 (26.0, 87.0) Time since diagnosis of PV, median, months 80.7 Male, % 57.7 Female, % 42.3 ECOG performance status, % 0 1 72.5 26.8 Hematocrit (%), median,(n=149) 43.0 n (%) < 40 ≥ 40 to ≤ 45 > 45 2 (1.3) 146 (98.0) 1 (0.7) WBC count (x 109/L), median (n=149) 10.6 n (%) ≤ 10 > 10 and ≤ 15 > 15 67 (45.0) 43 (28.9) 39 (26.2) PLT count (x 109/L), median (n=148) 420.0 n (%) < 100 ≥ 100 and < 400 ≥ 400 to < 600 ≥ 600 2 (1.3) 68 (45.6) 38 (25.5) 40 (26.8) JAK2 mutation, n (%) (n=149) Positive Negative Unknown 143 (96.0) 4 (2.7) 2 (1.3) MPN-SAF Symptom (n) Mean (SD) Total score (n=145) 2.0 (1.67) Fatigue (n=146) 3.6 (2.72) Early satiety (n=145) 1.8 (2.47) Abdominal discomfort (n=143) 1.7 (2.44) Inactivity (n=142) 2.1 (2.77) Concentration problem (n=146) 2.3 (2.75) Night sweats (n=145) 2.2 (3.07) Pruritus (n=145) 3.4 (3.37) Bone pain (n=144) 2.1 (2.89) Fever (n=144) 0.2 (0.92) Weight loss (n=142) 0.7 (1.72) Disclosures Passamonti: Novartis: Consultancy. Cavo:JANSSEN, CELGENE, AMGEN: Consultancy. Vannucchi:Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Other: Research Funding paid to institution (University of Florence), Research Funding; Shire: Speakers Bureau; Baxalta: Membership on an entity's Board of Directors or advisory committees. Bensasson:Novartis: Employment. Khan:Novartis: Employment. Mounedji:Novartis: Employment.
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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) | 0,002 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,003 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 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 ».