Polatuzumab Vedotin in Combination Treatment of Patients with R/R DLBCL

Clinical Studies with Polatuzumab Vedotin

Data presented in poster form at the ASH congress were based on extended follow-up of participants from two clinical trials. These included patients with DLBCL pre-treated with more than one line of previous therapy who could not undergo allogeneic HSCT. The phase Ib study evaluated the administration of pola-BR. The phase II study GO29356 was randomized and compared treatment with pola-BR to treatment with rituximab and bendamustine (BR) alone. The median follow-up duration was 46 months for the phase Ib study and 30 months for the phase II study. The median number of prior therapy lines was 2.

Efficacy

Phase Ib Study

In this study, which included 6 patients, 4 were alive at the time of data cutoff for this analysis, and 2 had discontinued treatment and died of disease progression. Three patients responded to treatment and remained in remission without further therapy. Their treatment response lasted a median of 44.6 months (range 28.9–44.6 months). The median progression-free survival (PFS) was 24.3 months. Overall survival (OS) could not yet be determined.

Phase II Study

In the study, 40 patients were treated with the pola-BR combination. A sustained response (complete or partial remission at least twice consecutively) was observed during the study in 19 (48%) patients. No association was found between sustained response lasting ≥ 12 months and clinical characteristics or the number of prior therapy lines in these patients. At the time of data cutoff, 31 patients had discontinued treatment. Fifteen patients died due to disease progression, and 10 due to an adverse event. A control group included 40 patients treated with the BR combination alone. A persistent therapeutic response was observed in 7 (18%) patients, and treatment was discontinued in 38 patients from this group. Nineteen of them died of disease progression, and 10 died due to adverse events. The median PFS in the pola-BR group compared to the BR group was 7.5 vs. 2.0 months (p < 0.0001), and median OS was 12.4 vs. 4.7 months (p = 0.0011).

Combined Analysis

Pooling data from both studies showed that the pola-BR regimen resulted in a sustained treatment response in 38% of patients for ≥ 12 months, and in 29% of patients for ≥ 24 months.

Safety of the Drug

The most common side effect in the pola-BR group was peripheral neuropathy, observed in 40% of patients. It was of maximum grade 2 intensity and mostly temporary. Secondary malignancy occurred in 4% of patients treated with pola-BR and in 5% of patients treated with BR. Both groups had similar frequencies of viral and bacterial infections.

Conclusion

Both studies demonstrated significantly better overall survival and progression-free survival in patients treated with the pola-BR regimen compared to the BR regimen. No new safety risks were identified. Polatuzumab vedotin in combination with the BR regimen has been approved by the U.S. Food and Drug Administration (FDA) and represents an effective treatment option for patients with relapsed or refractory DLBCL.

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Source: Sehn L. H., Matasar M. J., Flowers C. R. et al. Polatuzumab Vedotin Plus Bendamustine with Rituximab in Relapsed/Refractory Diffuse Large B-Cell Lymphoma: Updated Results of a Phase Ib/II Randomized Study. Poster 4081. 61^st ASH Annual Meeting, Orlando, Florida, 2019 Dec 9.