From the Journals

Adding polatuzumab extends survival in relapsed/refractory DLBCL



For patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), adding polatuzumab vedotin to bendamustine and rituximab can improve complete response rates and extend overall survival, according to findings from a phase 1b/2 trial.

Adding polatuzumab decreased mortality risk by 58%, reported lead author Laurie H. Sehn, MD, of the University of British Columbia, Vancouver, and colleagues.

Laurie H. Sehn

“Patients with transplantation-ineligible [relapsed/refractory] DLBCL, including those who experienced treatment failure with [autologous stem cell transplant], have dismal outcomes with limited therapeutic options,” the investigators wrote in the Journal of Clinical Oncology. “To our knowledge, this is the first randomized trial demonstrating an [overall survival] benefit in patients with transplantation-ineligible [relapsed/refractory] DLBCL.”

In the first part of the study, 27 patients were treated with polatuzumab vedotin, bendamustine, and obinutuzumab. After a median follow-up of 27 months, this regimen returned a complete response rate of 29.6%, median progression-free survival of 6.3 months, and median overall survival of 10.8 months.

In the primary analysis, 80 patients were randomized to receive bendamustine and rituximab, with or without polatuzumab. Adding polatuzumab had a significant benefit, as 40.0% of these patients achieved a complete response, compared with 17.5% of patients who did not receive polatuzumab. After a median follow-up of 22.3 months, outcomes also were significantly improved with the addition of polatuzumab for both median progression-free survival (9.5 vs. 3.7 months) and overall survival (12.4 vs. 4.7 months).

Adding polatuzumab did come with some safety trade-offs. Rates of certain grade 3 or 4 adverse events were higher, including thrombocytopenia (41% vs. 23.1%), neutropenia (46.2% vs. 33.3%), and anemia (28.2% vs. 17.9%), while infection rates were comparable. Almost half of the patients treated with polatuzumab (43.6%) developed grade 1 or 2 peripheral neuropathy, but most cases resolved.

Combination therapy with polatuzumab, bendamustine, and rituximab “represents a novel, effective therapeutic regimen to address the unmet need of patients with transplantation-ineligible [relapsed/refractory] DLBCL,” the investigators wrote. Since just 25% of polatuzumab combination–treated patients had received prior autologous stem cell transplant, the investigators said they could not make definitive conclusions on this combination’s efficacy in the post-ASCT setting.

Additional trials involving polatuzumab in the relapsed/refractory setting are ongoing. For patients with treatment-naive DLBCL, a phase 3 trial (NCT03274492) is evaluating substitution of polatuzumab for vincristine in the R-CHOP regimen.

The study was funded by F. Hoffmann-La Roche and Genentech. The investigators reported additional relationships with AbbVie, Kite Pharma, Lundbeck, and others.

SOURCE: Sehn LH et al. J Clin Oncol. 2019 Nov 6. doi: 10.1200/JCO.19.00172.

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