Adding atezolizumab to standard care may improve responses in patients with previously untreated diffuse large B-cell lymphoma (DLBCL), but this improvement is not substantial enough to warrant further study of the combination, according to researchers.1

Atezolizumab plus R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) produced a complete response (CR) rate that was higher than the CR rate observed in historical control individuals treated with R-CHOP alone. 

However, because the increase in CR was modest and atezolizumab appears to increase the incidence of adverse events (AEs) as well, further study of the combination is not warranted, the researchers concluded. They reported their findings in Blood Advances


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In this phase 1b/2 study (ClinicalTrials.gov Identifier: NCT02596971), researchers evaluated 42 patients with previously untreated DLBCL. Patients were treated with atezolizumab plus R-CHOP for 6 to 8 cycles. Those achieving a CR received consolidation therapy with atezolizumab.

At the data cutoff, the median observation time was 32.3 months. Forty of the 42 patients were evaluable for response. 

The CR rate at the end of induction was 77.5%, according to an independent review committee using modified Lugano 2014 criteria. The objective response rate (ORR) was 87.5% per the committee. 

The investigator-assessed ORR was 87.5%, and the investigator-assessed CR rate was 75.0%. At 3 years, the investigator-assessed progression-free survival (PFS) rate was 77.4%, and the overall survival rate was 87.2%. 

The researchers noted that the CR and PFS rates in this study were only slightly higher than those observed among patients who received R-CHOP alone in the phase 3 GOYA study.2 

The CR rate at the end of induction was 59.1% among R-CHOP recipients in GOYA, and the PFS rate at 18 months was 72.0% in this group. This is compared with the 77.5% CR rate and an 18-month PFS rate of 80.6% with atezolizumab plus R-CHOP in the current study.1

“A comparative study would be needed to ascertain whether the addition of atezolizumab to R-CHOP provides significant benefit versus R-CHOP alone, but the available data suggest efficacy differences between the two treatments are likely to be modest, and the additional AEs introduced by atezolizumab should be taken into consideration,” the researchers wrote. 

The safety of atezolizumab plus R-CHOP was manageable, according to the researchers. However, the combination was associated with AEs that are not typically associated with R-CHOP but are consistent with the known safety profile of atezolizumab, including elevated lipase (9.5%) and amylase (7.1%), hypothyroidism (7.1%), and pancreatitis (4.8%).

All patients had at least 1 AE, and the majority (76.2%) had a grade 3/4 AE. More than a third of patients (35.7%) discontinued the regimen due to AEs. 

Disclosures: This study was sponsored by F. Hoffmann-La Roche Ltd. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

References

1. 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. Published online October 26, 2022. doi:10.1182/bloodadvances.2022008344

2. Sehn LH, Martelli M, Trněný M, et al. A randomized, open-label, phase III study ofobinutuzumab or rituximab plus CHOP in patients with previously untreated diffuse large B-cell lymphoma: Final analysis of GOYA. J Hematol Oncol. 2020;13(1):71. doi:10.1186/s13045-020-00900-7