Triplet Combination Appears Well-Tolerated, Safe for DLBCL


Charles Herbaux, MD, MSc, CHRU de Lille, France, discusses results from the phase 2 GATA study, which evaluated the efficacy and safety of obinutuzumab, atezolizumab, and venetoclax in combination for relapsed/refractory diffuse large B-cell lymphoma (DLBCL). These results were presented during the virtual 2020 EHA Congress.


Hello. I'm Charles Herbaux from CHRU de Lille, France. I'm happy to give you here a brief overview of the results of the GATA study, a LYSA study multicenter, phase 2 trial evaluating a new combination in diffuse large B‑cell lymphoma, relapsed and refractory.

The rationale of this study is to combinate 3 drugs, which are obinutuzumab, atezolizumab, and venetoclax, to try to establish a virtual circle. 2 drugs are meant to kill cells directly, venetoclax and obinutuzumab. The 3rd drug is meant to enhance the effects with the help of anti‑tumor immunity, so hopefully, the mechanism with atezolizumab.

Inclusion and exclusion criteria are pretty standard with the diffuse large B-cell lymphoma, CD20 positive, of course, because of obinutuzumab.

The drugs were given first in an induction phase of 8 cycles where the obinutuzumab and atezolizumab were given IV every 3 weeks, and venetoclax orally each day, 800 milligrams per day. Then after this induction, we go to a maintenance phase with only atezolizumab and venetoclax.

Our primary end point was the overall metabolic response rate by Lugano Criteria at the end of induction, or of course at premature treatment discontinuation. We included 58 patients in this study. They were heavily pre‑treated with 2 prior lines of therapy or more for 83% of the patients and 63% of the patients were refractory to prior regimen.

The overall metabolic response rate was at 23.6%. We did observe a significantly higher overall metabolic response rate in patients with a lower tumor burden. When the highest mass was below 5 centimeters, this overall metabolic response rate was at 38.5%. Probably, the immunity needs smaller masses to be efficient and to be effective on all the cells.

In terms of safety, grade 3 or 4 adverse events were seen in 84% of the patients, and Grade 3 or more reported adverse events in at least 10% of the patients were pretty standard with venetoclax and obinutuzumab. There was mainly neutropenia, leukopenia, thrombocytopenia and anemia.

We did observe 2 immunologic adverse events probably related to atezolizumab. 1, hypothyroidism grade 1 and grade 3 autoimmune colitis. In a nutshell, this combination appears well-tolerated with no unexpected safety signal.

The overall metabolic response rates in this heavily pre‑treated population was relatively low, but probably more promising in the setting of the patient with a lower tumor burden.

I would like to thank, of course the LYSA and all the patients and their family, as well as all my co‑authors and most especially the co‑PI of this study, Professor Guillaume Cartron. Of course, thank you for your attention.   

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