Atezolizumab alone or in combination did not demonstrate a favorable risk-benefit profile in myelodysplastic syndrome

Abstract

We present here primary results from the phase Ib GO29754 study (NCT02508870) evaluating the safety and tolerability of atezolizumab, a PD-L1 inhibitor, alone and in combination with azacitidine, a hypomethylating agent (HMA), in patients with relapsed/refractory (R/R) or HMA-naïve myelodysplastic syndrome (MDS). R/R MDS patients received atezolizumab for 12 months (Cohort A), or atezolizumab plus azacitidine for six cycles followed by atezolizumab as maintenance for eight cycles (Cohort B). HMA-naïve MDS patients received atezolizumab plus azacitidine until loss of clinical benefit (Cohort C). Safety, activity, and exploratory endpoints were investigated. Forty-six patients were enrolled and received treatment (11 in Cohort A, 14 in Cohort B, 21 in Cohort C). All patients experienced ≥1 adverse event (AE) on study, and all patients discontinued atezolizumab. In Cohort A, seven patients (63.6%) died, and no patients responded. In Cohort B, eight patients (57.1%) discontinued azacitidine, 11 patients (78.6%) died, and two patients (14.3%) responded. In Cohort C, all 21 patients discontinued azacitidine, 13 patients died (61.9%), and 13 patients (61.9%) responded. The study was terminated by the sponsor prior to completing recruitment due to the unexpected high early death rate in Cohort C (6/13 deaths [46.2%] were due to AEs and occurred within the first four treatment cycles.). The high death rate and poor efficacy observed in this study do not support a favorable risk-benefit profile for atezolizumab as a single agent or in combination with azacitidine in R/R or HMA-naïve MDS.