Primary refractory plasmablastic lymphoma: A precision oncology approach

Hanno M Witte; Anke Fähnrich; Axel Künstner; Jörg Riedl; Stephanie M J Fliedner; Niklas Reimer; Nadine Hertel; Nikolas von Bubnoff; Veronica Bernard; Hartmut Merz; Hauke Busch; Alfred Feller; Niklas Gebauer

doi:10.3389/fonc.2023.1129405

Primary refractory plasmablastic lymphoma: A precision oncology approach

Front Oncol. 2023 Feb 27:13:1129405. doi: 10.3389/fonc.2023.1129405. eCollection 2023.

Authors

Hanno M Witte^{1

2}, Anke Fähnrich^{3

4

5}, Axel Künstner^{3

4

5}, Jörg Riedl^{1

6}, Stephanie M J Fliedner^{1

5}, Niklas Reimer^{3

4

5}, Nadine Hertel¹, Nikolas von Bubnoff^{1

5}, Veronica Bernard⁶, Hartmut Merz⁵, Hauke Busch^{3

4

5}, Alfred Feller⁶, Niklas Gebauer^{1

5}

Affiliations

¹ Department of Hematology and Oncology, University Hospital of Schleswig-Holstein, Lübeck, Germany.
² Department of Hematology and Oncology, Federal Armed Forces Hospital, Ulm, Germany.
³ Medical Systems Biology Group, Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany.
⁴ Institute for Cardiogenetics, University of Lübeck, Lübeck, Germany.
⁵ University Cancer Center Schleswig-Holstein, University Hospital of Schleswig- Holstein, Lübeck, Germany.
⁶ Hämatopathologie Lübeck, Reference Centre for Lymph Node Pathology and Hematopathology, Lübeck, Germany.

Abstract

Introduction: Hematologic malignancies are currently underrepresented in multidisciplinary molecular-tumor-boards (MTB). This study assesses the potential of precision-oncology in primary-refractory plasmablastic-lymphoma (prPBL), a highly lethal blood cancer.

Methods: We evaluated clinicopathological and molecular-genetic data of 14 clinically annotated prPBL-patients from initial diagnosis. For this proof-of-concept study, we employed our certified institutional MTB-pipeline (University-Cancer-Center-Schleswig-Holstein, UCCSH) to annotate a comprehensive dataset within the scope of a virtual MTB-setting, ultimately recommending molecularly stratified therapies. Evidence-levels for MTB-recommendations were defined in accordance with the NCT/DKTK and ESCAT criteria.

Results: Median age in the cohort was 76.5 years (range 56-91), 78.6% of patients were male, 50% were HIV-positive and clinical outcome was dismal. Comprehensive genomic/transcriptomic analysis revealed potential recommendations of a molecularly stratified treatment option with evidence-levels according to NCT/DKTK of at least m2B/ESCAT of at least IIIA were detected for all 14 prPBL-cases. In addition, immunohistochemical-assessment (CD19/CD30/CD38/CD79B) revealed targeted treatment-recommendations in all 14 cases. Genetic alterations were classified by treatment-baskets proposed by Horak et al. Hereby, we identified tyrosine-kinases (TK; n=4), PI3K-MTOR-AKT-pathway (PAM; n=3), cell-cycle-alterations (CC; n=2), RAF-MEK-ERK-cascade (RME; n=2), immune-evasion (IE; n=2), B-cell-targets (BCT; n=25) and others (OTH; n=4) for targeted treatment-recommendations. The minimum requirement for consideration of a drug within the scope of the study was FDA-fast-track development.

Discussion: The presented proof-of-concept study demonstrates the clinical potential of precision-oncology, even in prPBL-patients. Due to the aggressive course of the disease, there is an urgent medical-need for personalized treatment approaches, and this population should be considered for MTB inclusion at the earliest time.

Keywords: molecular tumor board; plasmablastic lymphoma; recurrent aberrations; targeted therapy; whole exome sequencing; whole transcriptome sequencing.