ATEZOLIZUMAB + OBINUTUZUMAB + VENETOCLAX IN PATIENTS WITH RELAPSED OR REFRACTORY INDOLENT NON-HODGKIN’S LYMPHOMA (R/R INHL): PRIMARY ANALYSIS OF A PHASE 2 TRIAL FROM LYSA.
Author(s): ,
Charles Herbaux
Affiliations:
CHU Montpellier,Montpellier,France
,
Emmanuel Bachy
Affiliations:
Hématologie,Lyon,France
,
Jean Marc Schiano de Colella
Affiliations:
IPC,Marseille,France
,
Stéphanie Guidez
Affiliations:
Hematology,Poitiers,France
,
Emmanuel Gyan
Affiliations:
Hematology,Tours,France
,
Rémy Gressin
Affiliations:
Hematology,Grenoble,France
,
Nadine Morineau
Affiliations:
Hematology,Vendée,France
,
Loic Ysebaert
Affiliations:
Hematology,Toulouse,France
,
Emmanuelle Nicolas Virelizier
Affiliations:
Hematology CLB,Lyon,France
,
Steven Le Gouill
Affiliations:
Hematology,Nantes,France
,
Karin Tarte
Affiliations:
CHU,Rennes,France
,
Hervé Tilly
Affiliations:
Hematology,Rouen,France
,
Roch Houot
Affiliations:
Hematology,Rennes,France
,
Gandhi Damaj
Affiliations:
Hematology,Caen,France
,
Sibon David
Affiliations:
Necker Hematology,Paris,France
,
Pierre Feugier
Affiliations:
Hematology,Nancy,France
,
Olivier Casasnovas
Affiliations:
Hematology,Dijon,France
,
Catherine Thieblemont
Affiliations:
St Louis Hematology,Paris,France
,
Corinne Haioun
Affiliations:
Mondor Hematology,Paris,France
,
Franck Morschhauser
Affiliations:
Hematology,Lille,France
,
Camille Laurent
Affiliations:
IUCT,Toulouse,France
Guillaume Cartron
Affiliations:
Hematology,Montpellier,France
EHA Library. Herbaux C. 06/09/21; 324620; S212
Charles Herbaux
Charles Herbaux
Contributions
Abstract
Presentation during EHA2021: All Oral presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: S212

Type: Oral Presentation

Session title: Indolent & mantle cell lymphoma - Clinical

Background
Relapsed and refractory (R/R) iNHL treatment remains challenging. Atezolizumab (ATE) and obinutuzumab (OBI) are monoclonal antibodies acting respectively to inhibit T-lymphocyte exhaustion or by inducing lymphoma cells cytotoxicity, whereas venetoclax (VEN) is a small molecule inhibiting BCL-2. Combining tumor-targeted therapies with agents that enhance anti-tumor immunity represents an attractive treatment paradigm. This LYSA sponsored multicenter phase 2 trial (NCT03276468) evaluated ATE, OBI and VEN combination in R/R B-cell lymphomas. Herein, we present primary efficacy and safety data from the iNHL cohort including Follicular Lymphoma (FL) and Marginal Zone Lymphomas (MZL). 

Aims
Evaluate the safety and efficacy of atezolizumab, obinutuzumab and venetoclax combination in R/R FL and MZL.

Methods
Patients ≥18 years with biopsy-confirmed R/R FL and MZL who failed at least one line of therapy were eligible. OBI was given IV at 1 g on day (D) 1, 8 and 15 of cycle (C) 1 and on D1 from C2 to C8 every 3 weeks. ATE was given IV, 1.2 g every 3 weeks, started at D2 of C1, then administered at D2 of each cycle for 24 cycles. VEN was given orally at 800 mg/D at full dose, starting on D8C1 for 24 cycles. The primary endpoint was the Overall Response Rate (ORR) evaluated by Lugano criteria at the end of induction (EOI) after 8 cycles of ATE, OBI and VEN (M6) or at premature treatment discontinuation. 

Results
At the time of the primary analysis (08 Jan 2021), 78 patients were enrolled. FL cohort (n=58): the median follow-up was 14.5 months. Main baseline characteristics were: Ann Arbor Stage III/IV, 85.7%; FLIPI HR, 47.3%; > 2 prior lines of therapy, 32.1%; and exposed to ASCT, 30.4%. The ORR on PET scan at EOI was measured at 53.6% [41.8%>65.1%], including 30.4% of CMR. 37 patients (63%) received the full induction treatment. MZL cohort (n=20; 13 nMZL, 5 eMZL, 2 sMZL): the median follow-up was 11.9 months. Main baseline characteristics were: Ann Arbor Stage IV, 100%; bone marrow infiltration, 38.9%; ≥ 2 extra-nodal sites, 50%; and > 2 prior lines of therapy, 22.2%. The ORR on CT scan at EOI was measured at 66.76% [44.6%>84.4%], including 16.7% of CR and 50.0% PR. 11 patients (55%) received the full induction treatment. At time of the present analysis, responses in the 2 cohorts seem durable with only 21,4% of responders who have reported relapse/progression. Out of the 78 pts, a total of 55 (70.5%) pts experienced grade 3–4 adverse event (AE) and 1 patient experienced an AE that led to discontinuation of any drug.  Main AE of grade 3 or more were hematologic cytopenias, with only one febrile neutropenia (1.3%). Three pts experienced immune-related AE (1 grade 2 myositis and 2 grade 3 colitis), no tumor lysis syndrome was observed.

Conclusion
ATE, OBI and VEN triplet appears to be well tolerated, with no unexpected toxicity brought by the combination. The ORR at EOI seems to be comparable to other innovative regiments in this setting, with durable responses to date.

Keyword(s): Follicular lymphoma, Immune therapy, Marginal zone, Targeted therapy

Presentation during EHA2021: All Oral presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: S212

Type: Oral Presentation

Session title: Indolent & mantle cell lymphoma - Clinical

Background
Relapsed and refractory (R/R) iNHL treatment remains challenging. Atezolizumab (ATE) and obinutuzumab (OBI) are monoclonal antibodies acting respectively to inhibit T-lymphocyte exhaustion or by inducing lymphoma cells cytotoxicity, whereas venetoclax (VEN) is a small molecule inhibiting BCL-2. Combining tumor-targeted therapies with agents that enhance anti-tumor immunity represents an attractive treatment paradigm. This LYSA sponsored multicenter phase 2 trial (NCT03276468) evaluated ATE, OBI and VEN combination in R/R B-cell lymphomas. Herein, we present primary efficacy and safety data from the iNHL cohort including Follicular Lymphoma (FL) and Marginal Zone Lymphomas (MZL). 

Aims
Evaluate the safety and efficacy of atezolizumab, obinutuzumab and venetoclax combination in R/R FL and MZL.

Methods
Patients ≥18 years with biopsy-confirmed R/R FL and MZL who failed at least one line of therapy were eligible. OBI was given IV at 1 g on day (D) 1, 8 and 15 of cycle (C) 1 and on D1 from C2 to C8 every 3 weeks. ATE was given IV, 1.2 g every 3 weeks, started at D2 of C1, then administered at D2 of each cycle for 24 cycles. VEN was given orally at 800 mg/D at full dose, starting on D8C1 for 24 cycles. The primary endpoint was the Overall Response Rate (ORR) evaluated by Lugano criteria at the end of induction (EOI) after 8 cycles of ATE, OBI and VEN (M6) or at premature treatment discontinuation. 

Results
At the time of the primary analysis (08 Jan 2021), 78 patients were enrolled. FL cohort (n=58): the median follow-up was 14.5 months. Main baseline characteristics were: Ann Arbor Stage III/IV, 85.7%; FLIPI HR, 47.3%; > 2 prior lines of therapy, 32.1%; and exposed to ASCT, 30.4%. The ORR on PET scan at EOI was measured at 53.6% [41.8%>65.1%], including 30.4% of CMR. 37 patients (63%) received the full induction treatment. MZL cohort (n=20; 13 nMZL, 5 eMZL, 2 sMZL): the median follow-up was 11.9 months. Main baseline characteristics were: Ann Arbor Stage IV, 100%; bone marrow infiltration, 38.9%; ≥ 2 extra-nodal sites, 50%; and > 2 prior lines of therapy, 22.2%. The ORR on CT scan at EOI was measured at 66.76% [44.6%>84.4%], including 16.7% of CR and 50.0% PR. 11 patients (55%) received the full induction treatment. At time of the present analysis, responses in the 2 cohorts seem durable with only 21,4% of responders who have reported relapse/progression. Out of the 78 pts, a total of 55 (70.5%) pts experienced grade 3–4 adverse event (AE) and 1 patient experienced an AE that led to discontinuation of any drug.  Main AE of grade 3 or more were hematologic cytopenias, with only one febrile neutropenia (1.3%). Three pts experienced immune-related AE (1 grade 2 myositis and 2 grade 3 colitis), no tumor lysis syndrome was observed.

Conclusion
ATE, OBI and VEN triplet appears to be well tolerated, with no unexpected toxicity brought by the combination. The ORR at EOI seems to be comparable to other innovative regiments in this setting, with durable responses to date.

Keyword(s): Follicular lymphoma, Immune therapy, Marginal zone, Targeted therapy

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