Venetoclax Shows Low Therapeutic Activity in BCL2-Positive Relapsed/Refractory Peripheral T-Cell Lymphoma: A Phase 2 Study of the Fondazione Italiana Linfomi

Laura Ballotta, Pier Luigi Zinzani, Stefano Pileri, Riccardo Bruna, Monica Tani, Beatrice Casadei, Valentina Tabanelli, Stefano Volpetti, Stefano Luminari, Paolo Corradini, Elisa Lucchini, Maria Chiara Tisi, Michele Merli, Alessandro Re, Marzia Varettoni, Emanuela Anna Pesce, Francesco Zaja, Laura Ballotta, Pier Luigi Zinzani, Stefano Pileri, Riccardo Bruna, Monica Tani, Beatrice Casadei, Valentina Tabanelli, Stefano Volpetti, Stefano Luminari, Paolo Corradini, Elisa Lucchini, Maria Chiara Tisi, Michele Merli, Alessandro Re, Marzia Varettoni, Emanuela Anna Pesce, Francesco Zaja

Abstract

Patients with relapsed/refractory (R/R) peripheral T-cell lymphoma (PTCL) have a poor prognosis, with an expected survival of less than 1 year using standard salvage therapies. Recent advances in our understanding of the biology of PTCL have led to identifying B-Cell Lymphoma 2 (BCL2) protein as a potential therapeutic target. BLC2 inhibitor venetoclax was investigated in a prospective phase II trial in patients with BCL2-positive R/R PTCL after at least one previous standard line of treatment (NCT03552692). Venetoclax given alone at a dosage of 800 mg/day resulted in one complete response (CR) and two stable diseases (SDs) among 17 enrolled patients. The majority of patients (88.2%) interrupted the treatment due to disease progression. No relationship with BCL2 expression was documented. At a median follow-up of 8 months, two patients are currently still on treatment (one CR and one SD). No case of tumor lysis syndrome was registered. Therefore, venetoclax monotherapy shows activity in a minority of patients whose biological characteristics have not yet been identified.

Clinical trial registration: www.clinicaltrials.gov (NCT03552692, EudraCT number 2017-004630-29).

Keywords: BCL2 inhibition; BCL2 protein; peripheral T-cell lymphoma; relapsed/refractory; venetoclax.

Conflict of interest statement

PZ has received advisory board fees from Secura Bio, Celltrion, Gilead, Janssen-Cilag, BMS, Servier, Sandoz, MSD, TG Therapeutics, Takeda, Roche, Eusapharma, Kyowa Kirin, Novartis, ADC Therapeutics, Incyte, and Beigene; received consultant fees from MSD, Eusapharma, and Novartis; and received speaker’s bureau fees from Celltrion, Gilead, Janssen-Cilag, BMS, Servier, MSD, TG Therapeutics, Takeda, Roche, Eusapharma, Kyowa Kirin, Novartis, Incyte, and Beigene. SL has received advisory board fees from Roche, BMS/Celgene, Gilead/kite, Jannsen, Genmab, and Regeneron. MV has received advisory board fees from Janssen, Beigene, and Roche and travel expenses from Abbvie. FZ has received advisory board fees from Roche, Celgene, Janssen, Sandoz, Gilead, Novartis, Abbvie, Amgen, Sobi, Argenx, and Grifols and received honoraria for giving lectures to medical meetings from Celgene, Janssen, Gilead, Novartis, Roche, Amgen, Abbvie, and Grifols. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Ballotta, Zinzani, Pileri, Bruna, Tani, Casadei, Tabanelli, Volpetti, Luminari, Corradini, Lucchini, Tisi, Merli, Re, Varettoni, Pesce and Zaja.

Figures

Figure 1
Figure 1
Positron emission tomography (PET) images before (A) and after (B) three cycles of venetoclax.
Figure 2
Figure 2
Overall survival (OS) and progression-free survival (PFS).

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