title: Prognostic factors and outcome of patients with hematological malignancies in phase I trials: the Gustave Roussy scoring system.
abstract: Despite considerable progress in hematological malignancies (HM) biology during the last decades, translation into clinical benefit remains a major challenge. To improve patient selection and identify patients most likely to benefit from phase I trials, we designed and validated, in an independent cohort, a simple prognostic score. Treatment outcome, toxicity, and survival data from 82 consecutive patients enrolled in 14 phase I trials were reviewed (January 2008-February 2012). We validated these results on a prospectively collected cohort (17 phase I trials, February 2012-May 2014, 88 patients). Within a median follow-up of 19.1 months (range: 2.1-43.8 months), the median progression-free and overall survival (OS) were, respectively, 4.1 months [95% confidence interval (CI): 3.0-5.3] and 19.8 months (95% CI: 16.1-36.8). Best overall response and disease control rates were similar to HM salvage regimens (28 and 64%, respectively). Through multivariate analysis of independent prognostic factors, we designed and prospectively validated a simple prognostic score based on histological subtype, performance status, and albumin. Patients with a low-risk score experienced significantly better OS compared with patients with an intermediate or a high score (median OS: 37 vs. 17 vs. 5 months; hazard ratio=11.68, 95% CI: 4.09-33.3). Our data indicate the safety and efficacy of phase I trials in a significant number of relapsed/refractory HM patients, with clinical benefit achieved in more than half of patients. Our simple scoring system offers a valuable selection tool encouraging HM patient inclusions in phase I trials.
authors.affiliation: Departments of aDrug Development bBiostatistics cMedical Oncology (Hematology), Gustave Roussy, Université Paris-Saclay, Villejuif, France.
authors.forename: Lina
authors.initials: L
authors.lastname: Benajiba
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Michot
authors.forename: Capucine
authors.initials: C
authors.lastname: Baldini
authors.forename: Laura
authors.initials: L
authors.lastname: Faivre
authors.forename: Andrea
authors.initials: A
authors.lastname: Varga
authors.forename: Rastilav
authors.initials: R
authors.lastname: Balheda
authors.forename: Anas
authors.initials: A
authors.lastname: Gazzah
authors.forename: Ecaterina
authors.initials: E
authors.lastname: Ileana
authors.forename: Sophie
authors.initials: S
authors.lastname: Postel-Vinay
authors.forename: Christophe
authors.initials: C
authors.lastname: Massard
authors.forename: Stéphane
authors.initials: S
authors.lastname: de Botton
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Soria
authors.forename: Vincent
authors.initials: V
authors.lastname: Ribrag
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects; D017321:Clinical Trials, Phase I as Topic / Q000379:methods*; D005260:Female; D019337:Hematologic Neoplasms / Q000175:diagnosis* / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012720:Severity of Illness Index; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents