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19.03.2020 | Original Article

Possible hampered effectiveness of second-line treatment with rituximab-containing chemotherapy without signs of rituximab resistance: a population-based study among patients with chronic lymphocytic leukemia

Annals of Hematology
Lina van der Straten, Arnon P. Kater, Jeanette K. Doorduijn, Esther C. van den Broek, Eduardus F.M. Posthuma, Avinash G. Dinmohamed, Mark-David Levin
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The online version of this article (https://​doi.​org/​10.​1007/​s00277-020-03994-8) contains supplementary material, which is available to authorized users.
Avinash G. Dinmohamed and Mark-David Levin contributed equally to this work.

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Rituximab-containing chemotherapy remains a viable frontline treatment option for patients with chronic lymphocytic leukemia (CLL) in the era of novel agents. However, its effectiveness in the second-line setting—in relation to previous rituximab exposure in first-line—has hardly been evaluated in a population-based setting. Therefore, in this comprehensive, population-based study, we assessed the impact of first-line treatment with rituximab-containing chemotherapy on the effectiveness of second-line treatment with rituximab-containing chemotherapy. We selected all 1735 patients diagnosed with CLL between 2004 and 2010 from the Dutch Population-based HAematological Registry for Observational Studies (PHAROS). The primary endpoint was treatment-free survival (TFS). First- and second-line treatment was instituted in 663 (38%) and 284 (43%) patients, respectively. In first line, the median TFS was 19.7 and 67.1 months for chemotherapy without (n = 445; 67%) and with rituximab (n = 218; 33%), respectively (adjusted hazard ratio [HRadjusted], 0.83; P = 0.031). The median TFS among recipients of second-line chemotherapy without (n = 165; 57%) and with rituximab (n = 121; 42%) was 15.0 and 15.3 months, respectively (HRadjusted, 0.93; P = 0.614). Of the 121 patients who received rituximab-containing chemotherapy in second-line, 89 (74%) and 32 (26%) received first-line chemotherapy without and with rituximab, respectively. Median TFS in these two treatment groups was 18.3 and 12.1 months, respectively (HRadjusted, 1.71; P = 0.060). Collectively, in this population-based study, the effectiveness of first-line treatment with rituximab-containing chemotherapy was less pronounced in second-line treatment. The hampered effectiveness of rituximab-containing chemotherapy in second-line could not be explained by previous rituximab exposure.

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