Universität zu Köln

Kaddu-Mulindwa, Dominic, Altmann, Bettina, Robrecht, Sandra, Ziepert, Morita, Regitz, Evi, Tausch, Eugen, Held, Gerhard, Poeschel, Viola, Lesan, Vadim, Bittenbring, Joerg Thomas ORCID: 0000-0003-3864-8315, Thurner, Lorenz, Pfreundschuht, Michael, Christofyllakis, Konstantinos ORCID: 0000-0002-0308-388X, Truemper, Lorenz, Loeffler, Markus, Schmitz, Norbert, Hoth, Markus ORCID: 0000-0001-7080-4643, Hallek, Michael ORCID: 0000-0002-7425-4455, Fischer, Kirsten, Stilgenbauer, Stephan, Bewarder, Moritz and Rixecker, Torben Millard (2022). KIR2DS1-HLA-C status as a predictive marker for benefit from rituximab: a post-hoc analysis of the RICOVER-60 and CLL8 trials. Lancet Haematol., 9 (2). S. E133 - 10. OXFORD: ELSEVIER SCI LTD. ISSN 2352-3026

Full text not available from this repository.

Abstract

Background The addition of rituximab to chemotherapy has substantially improved outcomes for patients with B-cell malignancies. The mechanisms of action of rituximab include activation of natural killer cells. Killer-cell immunoglobulin-like receptors (KIRs) mediate natural killer cell function through interaction with HLA. We evaluated the clinical impact of KIR-HLA genotypes on rituximab-containing therapy. Methods For this post-hoc analysis, we used data from the RICOVER-60 trial (NCT00052936) as the discovery cohort and the CLL8 trial (NCT00281918) as the validation cohort. RICOVER-60 included patients aged 61-80 years with aggressive B-cell lymphoma treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) with or without rituximab. CLL8 included patients aged 30-81 years with chronic lymphocytic leukaemia treated with chemotherapy (fludarabine and cyclophosphamide; FC) with or without rituximab. We evaluated the KIR and HLA-C status of 519 patients with available blood samples in the RICOVER-60 trial and the KIR2DS1 and HLA-C status of 549 patients with available blood samples in the CLL8 trial, and evaluated their associations with event-free survival (RICOVER-60), progression-free survival, and overall survival (RICOVER-60 and CLL8). Findings In the RICOVER-60 trial, 201 (39%) patients were positive for KIR2DS1, 79 (15%) were homozygous for HLA-C2, and 36 (7%) were positive for KIR2DS1 and homozygous for HLA-C2. In the CLL8 trial, 206 (38%) patients were positive for KIR2DS1, 75 (14%) were homozygous for HLA-C2, and 26 (5%) were positive for KIR2DS1 and homozygous for HLA-C2. In the RICOVER-60 trial, both KIR2DS1 and HLA-C status were identified as independent risk factors for survival. KIR2DS1 positivity, homozygosity for HLA-C2, and subsequent KIR2DS1-HLA-C status were associated with adverse clinical outcome in patients receiving rituximab-containing therapy (event-free survival for patients with KIR2DS1-HLA-C2/C2 vs all other patients, HR 2.6 [95% CI 1.4-4.7], p=0.0015; progression-free survival, 2.7 [1.5-5.1], p=0.0013; overall survival, 2.8 [1.5-5.4], p=0.0016) but not in patients receiving CHOP chemotherapy only (event-free survival, 0.9 [0.5-1.7], p=0.85; progression-free survival, 1.1 [0.6-2.0], p=0.81; overall survival, 1.2 [0.6-2.4], p=0.53). A significant interaction between KIR2DS1-HLA-C status and rituximab was observed (p=0.018 for event-free survival and p=0.034 for progression-free survival). In contrast to all other patients, those positive for KIR2DS1 and homozygous for HLA-C2 did not benefit from adding rituximab to CHOP chemotherapy (event-free survival, 1.9 [0.8-4.6], p=0.16; progression-free survival, 1.4 [0.6-3.4], p=0.48; overall survival, 1.6 [0.6-4.3], p=0.33). In the CLL8 trial, KIR2DS1-HLA-C status was confirmed as a predictive marker for benefit from rituximab therapy (p=0.024 for the interaction of KIR2DS1-HLA-C status and rituximab regarding progression-free survival). In contrast to all other patients, those positive for KIR2DS1 and homozygous for HLA-C2 did not benefit from adding rituximab to FC chemotherapy (progression-free survival, 2.1 [0.9-4.9], p=0.094; overall survival, 2.6 [0.5-12.7], p=0.21). Interpretation Assessment of KIR2DS1 and HLA-C genotype might identify patients who would not benefit from rituximab, thereby allowing alternative therapies to be given. Further validation of these findings in prospective clinical trials is needed.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kaddu-Mulindwa, Dominic UNSPECIFIED UNSPECIFIED UNSPECIFIED Altmann, Bettina UNSPECIFIED UNSPECIFIED UNSPECIFIED Robrecht, Sandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Ziepert, Morita UNSPECIFIED UNSPECIFIED UNSPECIFIED Regitz, Evi UNSPECIFIED UNSPECIFIED UNSPECIFIED Tausch, Eugen UNSPECIFIED UNSPECIFIED UNSPECIFIED Held, Gerhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Poeschel, Viola UNSPECIFIED UNSPECIFIED UNSPECIFIED Lesan, Vadim UNSPECIFIED UNSPECIFIED UNSPECIFIED Bittenbring, Joerg Thomas UNSPECIFIED orcid.org/0000-0003-3864-8315 UNSPECIFIED Thurner, Lorenz UNSPECIFIED UNSPECIFIED UNSPECIFIED Pfreundschuht, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Christofyllakis, Konstantinos UNSPECIFIED orcid.org/0000-0002-0308-388X UNSPECIFIED Truemper, Lorenz UNSPECIFIED UNSPECIFIED UNSPECIFIED Loeffler, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmitz, Norbert UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoth, Markus UNSPECIFIED orcid.org/0000-0001-7080-4643 UNSPECIFIED Hallek, Michael UNSPECIFIED orcid.org/0000-0002-7425-4455 UNSPECIFIED Fischer, Kirsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Stilgenbauer, Stephan UNSPECIFIED UNSPECIFIED UNSPECIFIED Bewarder, Moritz UNSPECIFIED UNSPECIFIED UNSPECIFIED Rixecker, Torben Millard UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-687817
DOI:	10.1016/S2352-3026(21)00369-0
Journal or Publication Title:	Lancet Haematol.
Volume:	9
Number:	2
Page Range:	S. E133 - 10
Date:	2022
Publisher:	ELSEVIER SCI LTD
Place of Publication:	OXFORD
ISSN:	2352-3026
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language B-CELL LYMPHOMA; NATURAL-KILLER-CELLS; CHEMOTHERAPY PLUS RITUXIMAB; RANDOMIZED CONTROLLED-TRIAL; ELDERLY-PATIENTS; KIR; CHOP; SELF; HLA; INDIVIDUALS Multiple languages Hematology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/68781