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Abstract

Abstract: S234

Type: Oral Presentation

Session title: Aggressive lymphomas: Prospective studies

Background

Despite major advances introduced by immunochemotherapy, relapse and refractory diffuse large B-cell lymphomas (R/R DLBCL) treatment remains challenging. Atezolizumab (ATE) and obinutuzumab (OBI) are monoclonal antibodies acting respectively to inhibit T-lymphocyte exhaustion (anti-PDL1) or by inducing lymphoma cells cytotoxicity (anti-CD20), 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.

Aims

GATA, a LYSA (Lymphoma Study Association) sponsored multicenter phase 2 trial (NCT03276468) evaluate the combination of ATE, OBI and VEN in R/R B lymphomas. We present here primary efficacy and safety data fromthe DLBCL cohort.

Methods

Patients ≥18 years with biopsy-confirmed R/R DLBCLwho failed at least one line of therapy (rituximab and anthracycline containing regimen) were eligible. OBI was given IV at the dose of 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, started on D8C1 for 24 cycles. The primary endpoint was the Overall Metabolic Response Rate (OMRR) 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 (03 Jan 2020), 58 patients were enrolled and the median follow-up was 9 months [6.9-11.8]. Baseline characteristics were: median age, 70 years; male, 53.4%; Ann Arbor Stage IV, 84.5%; aaIPI (≥2), 63.2%; >2 prior lines of therapy, 83.6%; and refractory to last line of prior regimen, 63.6%. The OMRR at EOI was measured at 23.6% [14.58%>34.93%], including 18% of CMR. To date, these responses seem durable with only 3 reported relapses. According to the highest diameter mass, OMRR was 38.5% versus 10.3%, <5cm and >5cm respectively; P = 0,02. Outcome of DLBCL patients was also analyzed according to the cell of origin as determined by immunohistochemistry, no difference was observed with a OMRR of 20.8% versus 25.0% (ns), in GC and non-GC subtypes respectively. All three treatments were stopped in 78% of patients, mostly for progressive disease. At the time of analysis, a median of 4 cycles [1-8] has been administered. A total of 48 (84.2%) patients experienced grade 3–4 adverse event (AE) and 6 (10.5%) had an AE that led to discontinuation of any drug. AE of grade 3 or more reported in at least 10% of patients were: neutropenia (33.3%), lymphopenia (35.1%), thrombocytopenia (17.5%) and anemia (10.5%). Of note, a grade 3 autoimmune colitis and a grade 1 hypothyroidism were reported during induction.

Conclusion

The ATE, OBI and VEN combination appears to be well tolerated. The OMRR rate at EOI is comparable with currently available treatment options in this population, with durable responses. The OMRR seems better in patients with a low tumor burden.

Session topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical

Keyword(s): Diffuse large B cell lymphoma, Targeted therapy

Abstract: S234

Type: Oral Presentation

Session title: Aggressive lymphomas: Prospective studies

Background

Despite major advances introduced by immunochemotherapy, relapse and refractory diffuse large B-cell lymphomas (R/R DLBCL) treatment remains challenging. Atezolizumab (ATE) and obinutuzumab (OBI) are monoclonal antibodies acting respectively to inhibit T-lymphocyte exhaustion (anti-PDL1) or by inducing lymphoma cells cytotoxicity (anti-CD20), 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.

Aims

GATA, a LYSA (Lymphoma Study Association) sponsored multicenter phase 2 trial (NCT03276468) evaluate the combination of ATE, OBI and VEN in R/R B lymphomas. We present here primary efficacy and safety data fromthe DLBCL cohort.

Methods

Patients ≥18 years with biopsy-confirmed R/R DLBCLwho failed at least one line of therapy (rituximab and anthracycline containing regimen) were eligible. OBI was given IV at the dose of 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, started on D8C1 for 24 cycles. The primary endpoint was the Overall Metabolic Response Rate (OMRR) 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 (03 Jan 2020), 58 patients were enrolled and the median follow-up was 9 months [6.9-11.8]. Baseline characteristics were: median age, 70 years; male, 53.4%; Ann Arbor Stage IV, 84.5%; aaIPI (≥2), 63.2%; >2 prior lines of therapy, 83.6%; and refractory to last line of prior regimen, 63.6%. The OMRR at EOI was measured at 23.6% [14.58%>34.93%], including 18% of CMR. To date, these responses seem durable with only 3 reported relapses. According to the highest diameter mass, OMRR was 38.5% versus 10.3%, <5cm and >5cm respectively; P = 0,02. Outcome of DLBCL patients was also analyzed according to the cell of origin as determined by immunohistochemistry, no difference was observed with a OMRR of 20.8% versus 25.0% (ns), in GC and non-GC subtypes respectively. All three treatments were stopped in 78% of patients, mostly for progressive disease. At the time of analysis, a median of 4 cycles [1-8] has been administered. A total of 48 (84.2%) patients experienced grade 3–4 adverse event (AE) and 6 (10.5%) had an AE that led to discontinuation of any drug. AE of grade 3 or more reported in at least 10% of patients were: neutropenia (33.3%), lymphopenia (35.1%), thrombocytopenia (17.5%) and anemia (10.5%). Of note, a grade 3 autoimmune colitis and a grade 1 hypothyroidism were reported during induction.

Conclusion

The ATE, OBI and VEN combination appears to be well tolerated. The OMRR rate at EOI is comparable with currently available treatment options in this population, with durable responses. The OMRR seems better in patients with a low tumor burden.

Session topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical

Keyword(s): Diffuse large B cell lymphoma, Targeted therapy

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