Atezolizumab Plus R-CHOP Therapy Among Patients With Previously Untreated DLBCL

Findings from a nonrandomized phase 1b/2 trial indicated that a regimen of atezolizumab, a humanized immunoglobulin G1 monoclonal antibody, plus the standard of care therapy of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) demonstrated clinical efficacy, with an improved complete response (CR) rate compared to historical controls among patients with previously untreated diffuse large B-cell lymphoma (DLBCL). 

However, study authors noted they do not plan to investigate this combination further, as, based on historical evidence, the efficacy differences between an atezolizumab plus R-CHOP regimen and a regimen of R-CHOP alone are unlikely to be significant, particularly once the additional adverse events of the addition of atezolizumab are considered.  

Anas Younes, MD, Memorial Sloan Kettering Cancer Center, New York, New York, and coauthors stated, “Atezolizumab has previously shown promising antitumor activity in several tumor types and hematologic malignancies.” They hypothesized, “the addition of atezolizumab to R-CHOP (atezo–R-CHOP) may enhance antitumor immune activation, leading to robust and long-lasting antitumor responses, with the potential to improve patient outcomes.” 

To assess this hypothesis, the study authors aimed to evaluate the efficacy and safety of an atezolizumab plus R-CHOP regimen followed by consolidation with single-agent atezolizumab among patients with previously untreated DLBCL. The primary endpoint was CR at the end of induction. 

42 patients with previously untreated DLBCL were enrolled in this trial and assessed for the safety and efficacy of atezolizumab plus R-CHOP therapy. Patients who achieved CR received consolidation therapy with atezolizumab for an additional 17 cycles. 

The CR rate at the end of induction was 77.5% (95% confidence interval [CI], 64.0 to 87.7; n = 40). At 3 years, the investigator-assessed PFS was 77.4% (95% CI, 59.7 to 88.0) and the overall survival rate was 87.2% (95% CI, 71.9 to 94.5). 100% of patients experienced ≥1 adverse event, with 76.2% (n = 32) experiencing grade 3 to 4 adverse events. A total of 5 deaths (11.9%) were reported, including 4 deaths (9.5%) because of PD, and 1 death (2.4%) considered to be related to atezolizumab and rituximab. 40.5% of patients (n = 17) experienced atezolizumab-related adverse events of special interest. 

Dr Younes et al concluded that the trial “demonstrated that the [atezolizumab]–R-CHOP combination provided durable clinical activity, and the safety profile was consistent with the known toxicities of the individual drugs.” 

Further comparative studies would be needed, Younes et al noted, to determine whether this regimen had an advantage over R-CHOP alone. “The available data suggest that the efficacy differences between the 2 treatments are likely to be modest, and the additional [adverse events] introduced by atezolizumab should be taken into consideration,” they explained. “Therefore, this combination will not be investigated further.”

Source: 

Younes A, Burke JM, Cheson BD, et al; Safety and efficacy of atezolizumab with rituximab and CHOP in previously untreated diffuse large B-cell lymphoma. Blood Adv 2023; 7 (8): 1488–1495. doi: 10.1182/bloodadvances.2022008344