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.
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