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
Author(s): ,
Lina Van Der Straten
Affiliations:
Research,Netherlands Comprehensive Cancer Organisation,Utrecht,Netherlands;Internal Medicine,Albert Schweitzer hospital,Dordrecht,Netherlands
,
Arnon P. Kater
Affiliations:
Hematology,Amsterdam UMC, University of Amsterdam,,Amsterdam,Netherlands
,
Jeanette K. Doorduijn
Affiliations:
Hematology,Erasmus MC Cancer Institute,Rotterdam,Netherlands
,
Esther C. Van den Broek
Affiliations:
PALGA,Houten,Netherlands
,
Eduardus F.M. Posthuma
Affiliations:
Internal Medicine,Reinier de Graaf hospital,Delft,Netherlands;Hematology,Leiden University Medical Center,Leiden,Netherlands
,
Avinash G. Dinmohamed
Affiliations:
Research,Netherlands Comprehensive Cancer Organisation,Utrecht,Netherlands;Hematology,Erasmus MC Cancer Institute,Rotterdam,Netherlands;Public Health,Erasmus University Medical Center,Rotterdam,Netherlands
Mark-David Levin
Affiliations:
Internal Medicine,Albert Schweitzer hospital,Dordrecht,Netherlands
EHA Library. van der Straten L. Jun 15, 2019; 266773; PS1156
Lina van der Straten
Lina van der Straten
Contributions
Abstract

Abstract: PS1156

Type: Poster Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 17:30 - 19:00

Location: Poster area

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.

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.

Session topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical

Keyword(s): Chemotherapy, Chronic lymphocytic leukemia, Population, Rituximab

By continuing to browse or by clicking “Accept Terms & all Cookies”, you agree to the storing of third-party cookies on your device to enhance your user experience and agree to the user terms and conditions of this learning management system (LMS).

Cookie Settings
Accept Terms & all Cookies