PS1156 HAMPERED EFFECTIVENESS OF SECOND‐LINE TREATMENT WITH RITUXIMAB‐BASED CHEMOTHERAPY WITHOUT SIGNS OF RITUXIMAB RESISTANCE: A POPULATION‐BASED STUDY AMONG PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA
Authors: Van Der Straten L. , Kater A.P. , Doorduijn J.K. , Van den Broek E.C. , Posthuma E.F. , Dinmohamed A.G. , Levin M.‐D. 
Published: June 2019

Background:Chemoimmunotherapy with rituximab is a well‐established treatment approach for patients with chronic lymphocytic leukemia (CLL) that still holds therapeutic value in this emerging era of novel agents, especially among specific patient subsets in the upfront setting. At present, the effectiveness of rituximab‐based chemoimmunotherapy as first salvage therapy is ill‐defined. Furthermore, it is unclear whether first‐line therapy with rituximab hampers the effectiveness of second‐line chemotherapy with rituximab.Aims:The aim of this population‐study was to assess the effectiveness of rituximab‐based chemotherapy, as compared to chemotherapy without rituximab, in first‐ and second‐line treatment. Special emphasis was put on the effectiveness of second‐line treatment with rituximab‐based chemotherapy with or without previous rituximab exposure.Methods:We selected all 1,735 CLL patients diagnosed in The Netherlands between 2004–2010 from the Dutch Population‐based Haematological Registry for Observational studies (PHAROS) in CLL, with follow‐up through December 31, 2014. We divided patients into three treatment cohorts, namely (1) first‐ and (2) second‐line treatment, and (3) rituximab‐based chemotherapy only in second‐line. The primary end point was treatment‐free survival (TFS). The Kaplan‐Meier method was used for time‐to‐event analyses and the log‐rank test to compare survival distributions in a univariable fashion. Multivariable evaluation of TFS was performed using Cox regression with adjustment for covariates (listed in Table 1). A P < 0.05 indicates statistical significance.Results:First‐ and second‐line treatment were initiated in 663 (38%) and 286 (16%) patients, respectively. Second‐line treatment with rituximab was applied in 121 (42%) patients, of whom 32 (26%) were previously exposed to rituximab and 89 (74%) were not. In first‐line treatment, median TFS was 19.7 and 67.1 months for chemotherapy without (n = 455; 67%) and with (n = 218; 33%) rituximab, respectively (P < 0.001; Fig 1A). Median TFS among recipients of second‐line chemotherapy without (n = 165) and with rituximab (n = 121) was 15.0 and 15.3 months, respectively (P = 0.318; Fig 1B). Of the 121 patients who received rituximab‐based chemoimmunotherapy in second‐line, median TFS was 18.3 and 12.1 months for those who received chemotherapy without (n = 89) and with (n = 32) rituximab in first‐line, respectively (P = 0.243; Fig 1C). The multivariable analysis confirmed the effectiveness of rituximab‐based chemotherapy in first‐line (treatment cohort 1), but failed to demonstrate a benefit in the second‐line setting (treatment cohort 2; Table 1). Furthermore, no evidence was found that prior rituximab exposure was associated with the effectiveness of rituximab‐based chemotherapy in second‐line (treatment cohort 3). Covariates associated with inferior TFS in that particular cohort were age per one‐year increase and first‐line therapy with a backbone of purine analogues, as compared with a backbone of alkylating agents. Conversely, patients with a longer time to next treatment had better TFS.Summary/Conclusion:In this comprehensive, population‐based study, the effectiveness of first‐line treatment with rituximab‐based chemotherapy was not objectivated in second‐line treatment. The lack of effectiveness of rituximab‐based chemotherapy in second‐line could not be explained by previous rituximab exposure.image