PhD Scientific Days 2024

Poster Session J - Pathological and Oncological Sciences 1.

Resistance mechanisms and clonal kinetics in mantle cell lymphoma treated with sequential BTKi and venetoclax therapy

Előadó neve

Dr. László, Tamás

Neptun code

JCUOZ7

Előadó munkahelye

HCEMM-SU Molecular Oncohematology Research Group, Department of Pathology and Experimental Cancer Research, Semmelweis University

Előadó telefonszáma

+36706704706

Előadó e-mail címe

laszlo.tamas@stud.semmelweis.hu

Az előadás címe

Resistance mechanisms and clonal kinetics in mantle cell lymphoma treated with sequential BTKi and venetoclax therapy

Szerző(k) neve és munkahelye

Tamás László¹, László I. Pinczés², Bence Bátai¹, Luca Varga¹, Botond Tímár¹, Donát Alpár¹, Ilona Tárkányi³, Márk Plander⁴, Zsolt Nagy³, Péter Rajnics⁵, Miklós Egyed⁵, Zsuzsa Molnár⁶, András Masszi⁶, Péter Tamáska⁷, Róbert Szász², Árpád Illés², Ferenc Magyari², Csaba Bödör¹

1: HCEMM-SU Molecular Oncohematology Research Group, Department of Pathology and Experimental Cancer Research, Semmelweis University
2: Division of Hematology, Department of Internal Medicine, University of Debrecen
3: Department of Internal Medicine and Hematology, Semmelweis University
4: Markusovszky University Teaching Hospital
5: Kaposi Mór University Teaching Hospital of County Somogy
6: National Institute of Oncology
7: Borsod-Abaúj-Zemplén County Hospital and University Teaching Hospital

Bemutatás módja

Poszter

Szekció

Poster Session J - Pathological and Oncological Sciences 1.

Language of the presentation

Hungarian

Preferred session

Pathological and Oncological Sciences

Összefoglaló szövege

Background: In recent years, targeted therapies including Bruton's tyrosine kinase inhibitors (BTKi) and the BCL2-antagonist venetoclax, have become the standard of care for refractory/relapsed mantle cell lymphoma (MCL). Although the mutational profile of MCL has been extensively studied, there is a lack of understanding regarding resistance mechanisms and genetic factors that impact the response to novel treatments in MCL.

Aims: In this study, we aimed to scrutinize the copy number profile and clonal dynamics of double-resistant MCL patients treated sequentially with BTKi and venetoclax using low-coverage whole genome sequencing (lcWGS).

Methods: Within this real-world study, serial formalin-fixed paraffin-embedded samples (n=21) were obtained from 12 patients diagnosed with MCL who underwent sequential BTKi and venetoclax therapy. Sequencing libraries were prepared using the NEBNext Ultra II DNA Library Prep Kit according to the manufacturer's instructions.

Results: Comparing the number of copy number alterations (CNAs) between samples collected before and after treatment initiation (n=21), we found significant differences as samples collected after treatment harbored significantly more CNAs (p=0.039; Wilcoxon test). Two out of three patients showing early progression on venetoclax displayed deletion of chromosome 9, whereas the alteration appeared in only 1/9 in the responsive cohort. In both cases with del(9p), the extent of the deletion encompassed the coding region of CDKN2A, major element of the SWI–SNF chromatin-remodeling complex. Furthermore, patient MCL#2 harbouring 4 sequential samples displayed a deletion of 9p21.3 consistently across the disease course. In this patient novel deletions were acquired at ibrutinib relapse and were also evident at venetoclax relapse, impacting the coding regions of SMARCA4-del(19) and DLC1 – del(8) underlining the pivotal role of del(9p) and del(8p23.2) in disease progression and therapy resistance.

Summary/Conclusion: Understanding the genetic foundation of resistance mechanisms in MCL is essential since patients who relapse on targeted treatment are experiencing poor clinical outcomes. This study used lcWGS, an innovative genome-wide approach, to assess the copy number variations of multidrug-resistant MCL samples, revealing putative primary and acquired resistance mechanisms.

University

Semmelweis University

Supervisor

Csaba Bödör

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

6905

Start

16:10

End

16:13