Effectiveness and Safety of Polatuzumab Vedotin Plus an Anti-CD20 Monoclonal Antibody (Rituximab or Obinutuzumab) and Zanubrutinib in Relapsed/Refractory Diffuse Large B-Cell Lymphoma.

BACKGROUND

Approximately 30% of patients with diffuse large B-cell lymphoma (DLBCL) relapse or are refractory to first-line treatment. This study aimed to determine the effectiveness and tolerability of the combination of Polatuzumab vedotin and Zanubrutinib plus Rituximab (Pola-ZR) or Obinutuzumab (Pola-ZG) in patients with relapsed/refractory (R/R) DLBCL.

METHODS

We conducted a prospective observational study as part of our registered cohort study (NCT06203652). Patients were planned to receive six 21-day cycles of Pola-ZR/G, followed by Zanubrutinib monotherapy. The primary endpoint was to evaluate the best overall response rate (BOR), while secondary endpoints included the median progression-free survival (mPFS), safety, and complete response rate (CRR). We collected data from 73 R/R DLBCL patients who received traditional salvage therapies (TST). After propensity score matching, they were paired 1:1 with the Pola-ZR/G arm to compare the effectiveness and survival outcomes.

RESULTS

Twenty-two patients were enrolled (median age 68 years) in the Pola-ZR/G group. After a median follow-up of 16.1 months, the investigators assessed BOR; it was 70% (77.77% for Pola-ZR and 63.6% for Pola-ZG cohort), and CRR was 45% in 20 evaluable R/R patients. The mPFS was 8.3 months and was higher compared to the TST cohort. The median overall survival (OS) of the Pola-ZR/G cohort had not been reached at the time of analysis. The most common grade 3 to 4 adverse events were infections of all types and hematological toxicity.

CONCLUSION

In our study, patients derived clinical benefit after receiving Pola-ZR/G compared to TST; the regimens had a tolerable safety profile in patients with R/R DLBCL.