Contributions
Abstract: EP543
Type: E-Poster Presentation
Session title: Aggressive Non-Hodgkin lymphoma - Clinical
Background
Relapsed/refractory (R/R) peripheral T-cell lymphoma (PTCL) patients have a poor prognosis with an expected survival of less than one year. Recent acknowledgement in the biology of PTCLs (Zaja F, et al. Am J Hematol 2016) lead to identification of BCL2 protein as a potential therapeutic target. Indeed, BCL2 is over-expressed in about 30% to 88% of PTCL patients. Venetoclax is an orally, selective BCL2 inhibitor with proved activity in B-cell malignancies.
Aims
FIL (Fondazione Italiana Linfomi) sponsored an open-label, multicenter, prospective, Simon two-stage, phase II study to determine the efficacy and safety of Venetoclax in R/R BCL2-positive PTCL.
Methods
Patients aged ≥18 years with biopsy-confirmed R/R PTCLs (PTCL not otherwise specified [PTCL-NOS], angioimmunoblastic T-cell lymphoma [AITL] and other nodal T-cell lymphomas of T-follicular helper origin [TFH]) with a percentage of BCL2 positive tumor cells ≥ 25% were included into the study. Venetoclax was administrated after 1 week ramp-up at 800mg once daily on 28-day cycles until progression or unacceptable toxicity. The primary endpoint was to evaluate the overall response rate (ORR) after the first 3 cycles according to the Lugano 2014 criteria. Treatment would have been considered active with an ORR 30% or more (according to the Simon two-stage design: 3 out of 18 patients of stage 1 phase and 7 out of overall 35 patients). Secondary objectives were to further assess the efficacy and to determine the safety of Venetoclax.
Results
Between May 2018 and November 2019, 17 patients were enrolled. Median age was 70 years (range 55-76) with 58.8% of males. Histologies were PTCL-NOS (76.5%) and AITL (23.5%). The majority (64.7%) had stage IV lymphoma and patients had received a median of 2 prior systemic therapies (range 1-15; in 8 patients > 2). ECOG performance status was > 1 in 29% of patients. We observed 1 complete response (6%) (CR) and 2 stable disease (12%) (SD) with an overall therapeutic activity in 3/17 patients (18%); at a median follow up of 8.2 months [0.85-17.5 months] two patients are currently still on treatment (1 CR and 1 SD). Because of the ORR rate < 30%, the enrollment was stopped. The majority of patients (76.4%) interrupted the treatment due to disease progression, all but one within cycle 5 of therapy. Median overall and progression free survival were 8.8 months (7.1-not reached) and 3.6 months (2-3.8), respectively. A total of 12 patients experienced grade 3-4 hematological toxicities: neutropenia (42%), thrombocytopenia (25%) and anemia (25%). Nine patients experienced grade 3 extra-hematological toxicities while no cases of tumor lysis syndrome were registered.
Conclusion
In this preliminary experience Venetoclax monotherapy showed therapeutic activity in a small proportion of patients with BCL2-positive R/R PTCL, with manageable toxicity. Better understanding of the mechanism of response might allow in the future to select patients to be treated with this agent.
This research was supported by a grant from AbbVie Srl.
Keyword(s): BCL2, T cell lymphoma
Abstract: EP543
Type: E-Poster Presentation
Session title: Aggressive Non-Hodgkin lymphoma - Clinical
Background
Relapsed/refractory (R/R) peripheral T-cell lymphoma (PTCL) patients have a poor prognosis with an expected survival of less than one year. Recent acknowledgement in the biology of PTCLs (Zaja F, et al. Am J Hematol 2016) lead to identification of BCL2 protein as a potential therapeutic target. Indeed, BCL2 is over-expressed in about 30% to 88% of PTCL patients. Venetoclax is an orally, selective BCL2 inhibitor with proved activity in B-cell malignancies.
Aims
FIL (Fondazione Italiana Linfomi) sponsored an open-label, multicenter, prospective, Simon two-stage, phase II study to determine the efficacy and safety of Venetoclax in R/R BCL2-positive PTCL.
Methods
Patients aged ≥18 years with biopsy-confirmed R/R PTCLs (PTCL not otherwise specified [PTCL-NOS], angioimmunoblastic T-cell lymphoma [AITL] and other nodal T-cell lymphomas of T-follicular helper origin [TFH]) with a percentage of BCL2 positive tumor cells ≥ 25% were included into the study. Venetoclax was administrated after 1 week ramp-up at 800mg once daily on 28-day cycles until progression or unacceptable toxicity. The primary endpoint was to evaluate the overall response rate (ORR) after the first 3 cycles according to the Lugano 2014 criteria. Treatment would have been considered active with an ORR 30% or more (according to the Simon two-stage design: 3 out of 18 patients of stage 1 phase and 7 out of overall 35 patients). Secondary objectives were to further assess the efficacy and to determine the safety of Venetoclax.
Results
Between May 2018 and November 2019, 17 patients were enrolled. Median age was 70 years (range 55-76) with 58.8% of males. Histologies were PTCL-NOS (76.5%) and AITL (23.5%). The majority (64.7%) had stage IV lymphoma and patients had received a median of 2 prior systemic therapies (range 1-15; in 8 patients > 2). ECOG performance status was > 1 in 29% of patients. We observed 1 complete response (6%) (CR) and 2 stable disease (12%) (SD) with an overall therapeutic activity in 3/17 patients (18%); at a median follow up of 8.2 months [0.85-17.5 months] two patients are currently still on treatment (1 CR and 1 SD). Because of the ORR rate < 30%, the enrollment was stopped. The majority of patients (76.4%) interrupted the treatment due to disease progression, all but one within cycle 5 of therapy. Median overall and progression free survival were 8.8 months (7.1-not reached) and 3.6 months (2-3.8), respectively. A total of 12 patients experienced grade 3-4 hematological toxicities: neutropenia (42%), thrombocytopenia (25%) and anemia (25%). Nine patients experienced grade 3 extra-hematological toxicities while no cases of tumor lysis syndrome were registered.
Conclusion
In this preliminary experience Venetoclax monotherapy showed therapeutic activity in a small proportion of patients with BCL2-positive R/R PTCL, with manageable toxicity. Better understanding of the mechanism of response might allow in the future to select patients to be treated with this agent.
This research was supported by a grant from AbbVie Srl.
Keyword(s): BCL2, T cell lymphoma