Journal article
Targeting of inflammatory pathways with R2CHOP in high-risk DLBCL
Leukemia, Vol.35(2), pp.522-533
02/2021
DOI: 10.1038/s41375-020-0766-4
PMCID: PMC7483252
PMID: 32139889
Abstract
Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma, and front line therapies have not improved overall outcomes since the advent of immunochemotherapy. By pairing DNA and gene expression data with clinical response data, we identified a high-risk subset of non-GCB DLBCL patients characterized by genomic alterations and expression signatures capable of sustaining an inflammatory environment. These mutational alterations (PIM1, SPEN, and MYD88 [L265P]) and expression signatures (NF-κB, IRF4, and JAK-STAT engagement) were associated with proliferative signaling, and were found to be enriched in patients treated with RCHOP that experienced unfavorable outcomes. However, patients with these high-risk mutations had more favorable outcomes when the immunomodulatory agent lenalidomide was added to RCHOP (R2CHOP). We are the first to report the genomic validation of a high-risk phenotype with a preferential response towards R2CHOP therapy in non-GCB DLBCL patients. These conclusions could be translated to a clinical setting to identify the ~38% of non-GCB patients that could be considered high-risk, and would benefit from alternative therapies to standard RCHOP based on personalized genomic data.
Details
- Title: Subtitle
- Targeting of inflammatory pathways with R2CHOP in high-risk DLBCL
- Creators
- Keenan T Hartert - Mayo Clinic in FloridaKerstin Wenzl - Mayo Clinic in FloridaJordan E Krull - Mayo Clinic in FloridaMichelle Manske - Mayo Clinic in FloridaVivekananda Sarangi - Mayo Clinic in FloridaYan Asmann - Mayo Clinic in FloridaMelissa C Larson - Mayo Clinic in FloridaMatthew J Maurer - Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USASusan Slager - Mayo Clinic in FloridaWilliam R Macon - Mayo ClinicRebecca L King - Mayo Clinic in FloridaAndrew L Feldman - Mayo Clinic in FloridaAnita K Gandhi - Summit (United Kingdom)Brian K Link - University of IowaThomas M Habermann - Mayo ClinicZhi-Zhang Yang - Mayo Clinic in FloridaStephen M Ansell - Mayo ClinicJames R Cerhan - Mayo Clinic in FloridaThomas E Witzig - Division of Hematology, Mayo Clinic, Rochester, USA,Grzegorz S Nowakowski - Mayo ClinicAnne J Novak - Division of Hematology, Mayo Clinic, Rochester, USA,
- Resource Type
- Journal article
- Publication Details
- Leukemia, Vol.35(2), pp.522-533
- DOI
- 10.1038/s41375-020-0766-4
- PMID
- 32139889
- PMCID
- PMC7483252
- NLM abbreviation
- Leukemia
- ISSN
- 0887-6924
- eISSN
- 1476-5551
- Grant note
- U01 CA195568 / NCI NIH HHS T32 AI007425 / NIAID NIH HHS R01 CA212162 / NCI NIH HHS P30 CA086862 / NCI NIH HHS P30 CA015083 / NCI NIH HHS P50 CA097274 / NCI NIH HHS
- Language
- English
- Date published
- 02/2021
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Epidemiology; Internal Medicine
- Record Identifier
- 9984360153102771
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