The prognosis of Diffuse Large B cell Lymphoma (DLBCL) patients with an early relapse is dismal. Atezolizumab has shown promising activity in relapsed DLBCL patients. Toxicity data on atezolizumab are available for \> 6000 patients and is manageable. The assumption of this study is that atezolizumab consolidation will result in higher disease free survival by eradicating minimal residual disease In melanoma and lung cancer consolidation immunotherapy after chemoradiotherapy has shown an increase in survival.
In high risk diffuse large B-cell lymphoma (DLBCL), International Prognostic Index (IPI)-score ≥ 3 21% of patients will relapse within 2-years after completion of R-CHOP induction treatment despite achieving a complete remission. Patient relapsing within a year after R-CHOP treatment have a very poor prognosis, even after second line chemotherapy, with only 15% of patients achieving a long remission. Therefore, additional therapy in first line treatment is required for these patients. The immune checkpoint inhibitor atezolizumab is a monoclonal antibody directed against the program death ligand 1 (PDL1). The PD1 and PDL1 inhibitors have shown excellent results in relapsed Hodgkin lymphoma and promising results in relapsed B-cell non Hodgkin lymphoma. Given the acceptable toxicity profile of atezolizumab, this study examines the efficacy and toxicity of atezolizumab as consolidation treatment after R-CHOP induction in DLBCL patients at high risk of relapse.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
109
Intervention Atezolizumab starts after 6 - 8 R-CHOP induction cycles (Rituximab, Cyclophosphamide, Hydroxo-doxorubicin, Vincristine and Prednisone (R-CHOP)); 18 cycles Atezolizumab followed by 12 months of observation
BE-Antwerpen Edegem-UZA
Antwerp, Belgium
BE-Antwerpen-ZNASTUIVENBERG
Antwerp, Belgium
BE-Brugge-AZBRUGGE
Bruges, Belgium
BE-Leuven-UZLEUVEN
Leuven, Belgium
BE-Roeselare-AZDELTA
Roeselare, Belgium
NL-Den Bosch-JBZ
's-Hertogenbosch, Netherlands
NL-Amersfoort-MEANDERMC
Amersfoort, Netherlands
NL-Amsterdam-OLVG
Amsterdam, Netherlands
NL-Amsterdam-VUMC
Amsterdam, Netherlands
NL-Apeldoorn-GELREAPELDOORN
Apeldoorn, Netherlands
...and 22 more locations
Disease free survival (DFS) measured from the date of registration to relapse or death from any cause whichever comes first.
To evaluate the 2-year DFS for patients in complete metabolic remission after R-CHOP induction
Time frame: 2 year after inclusion last patient
(Severe) Adverse Events and the relation of adverse events in time to the recovery of the T-cell repertoire.
To evaluate toxicity and assess the relation of adverse events in time to recovery of the T-cell repertoire.
Time frame: 2 years after inclusion last patient
Overall survival (OS), calculated from registration until death from any cause. Patients still alive or lost to follow up are censored at the last date known to be alive.
To evaluate the 2-year OS.
Time frame: 2 years after inclusion last patient
The relationship between MRD status at the end-of-induction and end-of-consolidation therapy.
To evaluate MRD status at the end of induction therapy, at various time points during consolidation treatment and at the end of consolidation.
Time frame: 2 years after inclusion last patient
The relation between MRD conversion and 2-years DFS and OS.
To evaluate if there is a relation between MRD conversion and 2-years DFS and OS.
Time frame: 2 years after inclusion last patient
The relation between the T-cell and NK cell repertoire and adverse events.
To evaluate the recovery of the T-cell and NK cell repertoire after induction therapy and at various time points during consolidation treatment in relation to toxicity and efficacy.
Time frame: 2 years after inclusion last patient
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