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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

Zeitschrift:
Annals of Hematology
Autoren:
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
Wichtige Hinweise

Electronic supplementary material

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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Abstract

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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