Outcomes and prognostic factors for relapsed or refractory lymphoma patients in phase I clinical trials

Jean Marie Michot, Lina Benajiba, Laura Faivre, Capucine Baldini, Lelia Haddag, Clement Bonnet, Christophe Massard, Frederic Bigot, Camille Bigenwald, Benjamin Verret, Zoé A.P. Thomas, Andrea Varga, Anas Gazzah, Antoine Hollebecque, David Ghez, Julien Lazarovici, Rastilav Balheda, Aurore Jeanson, Sophie Postel-Vinay, Alina DanuJean Charles Soria, Xavier Paoletti, Vincent Ribrag

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3 Scopus citations


Background Although safety and prognostic factors for overall survival (OS) have been extensively studied in Phase I clinical trials on patients with solid tumours, data on lymphoma trials are scarce. Here, we investigated safety, outcomes and prognostic factors in relapsed or refractory lymphoma patients included in a series of Phase I trials. Method and patients All consecutive adult patients with recurrent/refractory lymphoma enrolled in 26 Phase I trials at a single cancer centre in France between January 2008 and June 2016 were retrospectively assessed. Results 133 patients (males: 65%) were included in the analysis. The median (range) age was 65 (23–86). Aggressive non-Hodgkin, indolent non-Hodgkin and Hodgkin types accounted for 64%, 25% and 11% of the patients, respectively. The patients had received a median (range) of 3 (1–13) lines of treatment prior to trial entry. The median [95% confidence interval] progression-free survival and OS times were 3.0 [1.8–3.6] and 17.8 [12.7–30.4] months, respectively. High-grade toxicity (grade 3 or higher, according to the National Cancer Institute’s Common Terminology Criteria for Adverse Events classification) was experienced by 56 of the 133 patients (42%) and was related to the investigational drug in 44 of these cases (79%). No toxicity-related deaths occurred. Dose-limiting toxicity (DLT) was encountered in 11 (9%) of the 116 evaluable patients. High-grade toxicity occurred during the DLT period for 34 of the 56 patients (61%) and after the DLT period in the remaining 22 (39%). The main prognostic factors for poor OS were the histological type (i.e. tumour aggressiveness), an elevated serum LDH level, and a low serum albumin level. Early withdrawal from a trial was correlated with the performance status score, the histological type and the serum LDH level. The overall objective response and disease control rates were 24% and 57%, respectively. Conclusion Performance status, LDH, albumin and histological type (tumour aggressiveness) appear to be the most relevant prognostic factors for enrolling Phase I participants with relapsed or refractory lymphoma. 39% of the patients experienced a first high-grade toxic event after the dose-limiting toxicity period, suggesting that the conventional concept of dose-limiting toxicity (designed for chemotherapy) should be redefined in the era of modern cancer therapies.

Original languageEnglish
Pages (from-to)62-74
Number of pages13
JournalInvestigational New Drugs
Issue number1
StatePublished - 1 Feb 2018
Externally publishedYes


  • Dose-limiting toxicity
  • Phase I clinical trial
  • Recommended phase II dose
  • Relapsed and refractory lymphoma
  • Study design


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