New Alternative in the Treatment of Diffuse Large B-cell Lymphoma
For patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not suitable candidates for autologous stem cell transplantation, a wide range of treatment regimens is available. Recently, the addition of polatuzumab vedotin to rituximab and bendamustine therapy has shown promising efficacy in both registration studies and real-world clinical practice.
Treatment of Patients with Relapsed or Refractory DLBCL
The prognosis for DLBCL patients treated with immunochemotherapy is relatively good, with more than half achieving 10-year survival. Most patients are treated in the 1st line with a combination of rituximab (anti-CD20 antibody) with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Approximately 60% of patients are completely cured with R-CHOP, while about a third relapse on the treatment.
Following relapse, autologous stem cell transplantation (ASCT) is typically used if possible. Patients unable to undergo transplantation are treated with platinum-based immunochemotherapy. Recently, the polatuzumab vedotin (an anti-CD79b antibody-drug conjugate) in combination with rituximab and the alkylating cytostatic bendamustine (pola-BR regimen) has also been registered.
Pola-BR Increases Overall Survival Compared to BR
In the GO29365 registration study, the pola-BR regimen in patients pre-treated with at least one line showed a statistically significant longer median overall survival compared to bendamustine/rituximab therapy (OS: 12.4 vs. 4.4 months; hazard ratio [HR] 0.42; p = 0.0023). The median progression-free survival (PFS) was 7.5 months in the pola-BR group compared to 2 months in the BR group (HR 0.33; p < 0.0001). The safety profile of pola-BR was similar to that of BR.
Data from real-world clinical practice (retrospective studies conducted in Germany and Israel) report a median OS of approximately 7–8 months for the pola-BR regimen. In the Czech Republic, 21 patients received pola-BR within a specific treatment program, achieving an OS of 8.7 months despite having worse baseline characteristics than those in the registration study.
Incorporation of Pola-BR into the Therapeutic Algorithm
The Czech guidelines recommend using platinum-based salvage chemotherapy for relapsed DLBCL patients suitable for stem cell transplantation and proceeding with ASCT once remission is achieved. If patients respond poorly to salvage therapy, gemcitabine-based regimens or pola-BR can be used as a bridge to ASCT or CAR-T cell therapy.
For patients unsuitable for transplantation, pola-BR can be used in the 1st line after relapse, potentially as a bridge to CAR-T cell therapy or in subsequent lines of treatment after relapse on a gemcitabine regimen.
Conclusion
Approximately 10% of DLBCL patients are primarily refractory, with 30–40% relapsing after 1st line treatment. Pola-BR appears to be an effective alternative for patients with relapsed/refractory disease who are not suitable candidates for ASCT. This treatment regimen can also be used as a bridge in preparation for autologous transplantation or CAR-T therapy.
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Source: Trněný M., Janíková A., Procházka V. et al. Polivy – A New Alternative in the Treatment of DLBCL. Hot Topics in Oncology from the Perspective of Czech Doctors 2020; 5 (5): 305–309.
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