In an analysis reported in a letter to the editor in The New England Journal of Medicine, Palmer et al identified evidence that polatuzumab vedotin-piiq–containing regimens were preferentially effective among patients with diffuse large B-cell lymphoma (DLBCL) with activated B cell (ABC) vs germinal center B cell (GCB) as the cell of origin.
Study Details
As described by the investigators, the phase III POLARIX study recently showed that polatuzumab vedotin combined with rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) significantly improved progression-free survival vs rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in previously untreated patients with DLBCL. Progression-free survival events had occurred in 24% vs 31% of patients (hazard ratio [HR] = 0.73, 95% confidence interval [CI] = 0.57–0.95, P = .0177). The study supported the April 2023 approval of polatuzumab vedotin together with R-CHP in this setting.
The current analysis evaluated the differential efficacy of polatuzumab vedotin–containing regimens based on the cell of origin in studies in patients with DLBCL.
Key Findings
In five studies performed prior to POLARIX that involved patients with relapsed or refractory DLBCL, polatuzumab vedotin–containing regimens produced objective responses in a significantly greater proportion of patients with ABC vs GCB tumors (P < .001); the probability of response ranged from 25% to 50% for GCB tumors vs 50% to 80% for ABC tumors.
As stated by the investigators, data from POLARIX presented at the U.S. Food and Drug Administration Oncologic Drugs Advisory Committee meeting showed a significant benefit of Pola-R-CHP among patients with ABC tumors: the hazard ratio for disease progression, relapse, or death for Pola-R-CHP vs R-CHOP was 0.34 (95% CI = 0.13–0.85), and the hazard ratio for death was 0.27 (95% CI = 0.06–1.26) among these patients. Among patients with GCB tumors, the hazard ratio for disease progression, relapse, or death was 1.18 (95% CI = 0.75–1.84), and the hazard ratio for death was 1.64 (95% CI = 0.87–3.07).
Pooled analysis of the POLARIX trial and a randomized phase II trial evaluating the addition of polatuzumab vedotin to bendamustine/rituximab in the relapsed/refractory setting showed that the benefit of polatuzumab vedotin was significantly greater among patients with ABC vs GCB tumors; a difference by a factor of 3.8 in the hazard ratio for disease progression, relapse, or death and a difference by a factor of 5.0 in the hazard ratio for death were observed (P < .001 for both comparisons).
The investigators concluded: “These findings indicate that the modest overall benefit with respect to progression-free survival in the POLARIX trial arises from a large benefit in non-GCB tumors, diluted by no benefit in GCB tumors. Pola-R-CHP appears to be remarkably beneficial for ABC DLBCL. Conversely, GCB DLBCL may more appropriately continue to be treated with R-CHOP….”
Ash A. Alizadeh, MD, PhD, of Stanford University School of Medicine, is the corresponding author of The New England Journal of Medicine article.
Disclosure: For full disclosures of the study authors, visit nejm.org.
