Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma

1. Polatuzumab vedotin in combination with bendamustine and rituximab yielded higher complete response rates than bendamustine and rituximab alone.

Evidence Rating Level: 1 (Excellent)

Diffuse large B-cell lymphoma (DLBCL) is often curable, but a portion of patients are refractory to, or relapse after, treatment with the current standard of care (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone chemoimmunotherapy). Some of these relapsed/refractory (R/R) patients are cured with autologous stem-cell transplantation (ASCT), but few options exist for patients who are ineligible for ASCT. Polatuzumab vedotin, a CD79b-targeted antibody conjugate delivering monomethyl auristatin E, a microtubule inhibitor, has demonstrated encouraging activity in this setting, thus there is impetus to combine it with CD20-targeted agents such as obinutuzumab and rituximab. These combinations were tested in the present phase Ib/II study. In the phase Ib study, the safety and efficacy of polatuzumab vedotin with bendamustine and obinutuzumab (pola-BG) and polatuzumab vedotin with bendamustine and rituximab (pola-BR) was evaluated in 6 and 6 patients with R/R DLBCL who are inelibible for ASCT, respectively. In the randomized, controlled phase II portion, an expansion cohort evaluating pola-BG (21 patients) and a randomly assigned cohort (80 patients; 40 per treatment arm) comparing pola-BR with BR alone, were studied to determine the complete response (CR) rate of pola-BR versus BR as measured by PET-CT. Researchers found that the phase Ib/II pola-BG cohort (n = 27) had a CR rate of 29.6% and a median OS of 10.8 months (median follow-up, 27.0 months). In the randomized cohort (pola-BR and BR groups), pola-BR patients had a significantly higher CR rate (40.0% vs. 17.5%, p=0.026) and longer progression-free survival (median 9.5 vs. 3.7 months, HR 0.36, 95% CI 0.21 to 0.63, p=0.001) and overall survival (median 12.4 vs. 4.7 months, HR 0.42, 95% CI 0.24 to 0.75, p=0.002; median follow-up, 22.3 months) than BR patients. Overall, the small number of patients in the pola-BG cohort made estimation of the true CR rate difficult, but there was no indication of benefit of obinutuzumab over rituximab in this setting. Pola-BR patients had higher rates of grade 3-4 neutropenia (46.2% vs. 33.3%), anemia (28.2% vs. 17.9%), and thrombocytopenia (41% vs. 23.1%), but similar grade 3-4 infections (23.1% vs. 20.5%), as compared with the BR group. Pola-BG had a tolerable safety profile. In summary, this study supports a role for polatuzumab vedotin in combination with BR, but larger studies are required to validate the clinical efficacy of this therapeutic approach.

Click to read the study in Journal of Clinical Oncology

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