PracticeUpdate Oncology Best of 2018

CONFERENCE COVERAGE 30

Response Rates Improve SignificantlyWith Three-Drug Combination for DLBCL Adding polatuzumab vedotin to bendamustine and rituximab resulted in a significantly higher rate of

complete responses by PET scan. I n patients with diffuse large B-cell lym- phoma (DLBCL), adding polatuzumab vedotin (pola) to bendamustine and rituximab (BR) treatment resulted in a signif- icantly higher rate of complete responses by positron emission tomography (PET) and notably longer progression-free survival (PFS) and overall survival (OS) compared to BR alone. This finding held regardless of prior treatment status, new research shows. The study met its primary endpoint, demon- strating that the addition of pola to BR increased complete response rates from 15% to 40% (P = .012) at the end of treatment, as measured by PET scan and assessed by an independent review committee (IRC). No unexpected safety signals were observed with the addition of pola to BR.

In total, 80 FL and 80 DLBCL transplant-in- eligible patients were randomized 1:1 to pola 1.8 mg/kg + BR (B: 90mg/m 2 x 2 days; R: 375mg/m 2 ) or BR for 6 cycles (q28 days FL, q21 days DLBCL). Patients were stratified by duration of response to last treatment ≤12 months or >12 months. FL patients were also stratified by high vs low disease burden. For FL patients (pola+BR vs BR), median age was 65 vs 63 years, both arms had median 2 prior therapies, 41% vs 42% were refractory to last therapy, and 64% vs 37% had FLIPI 3–5. As of October 20 17, median follow up was 15 months. DLBCL charac- teristics and follow-up were previously described (Sehn, ASH 2017). No unexpected safety signals were observed with the addition of pola to BR. The most common Grade 3–4 adverse events with pola + BR compared to BR alone, respectively, were low white blood cell count (46.2% vs 35.9%), low white blood cell count with fever (10.3% vs 5.1%), low platelet count (33.3% vs 20.5%), ane- mia (25.6% vs 12.8%), and infections (17.9% vs 17.9%). Cytopenias, febrile neutropenia, and infections were the most common grade 3–5 adverse events that were higher in pola+BR vs BR in both FL and DLBCL. Seri- ous adverse effects higher in pola+BR vs BR were febrile neutropenia (FL, DLBCL) and infection (FL). Grade 5 rates were sim- ilar between treatment arms per histology: 5% (FL) and 18% (DLBCL). The complete response rate by PET scan by IRC and PFS by investigator were simi- lar between FL arms. In DLBCL, pola + BR showed significantly higher rates (P = .012), longer median for PFS by investigator (P < .0001), and OS (mOS; P = .0008). Also in DLBCL, longer PFS and OS were seen for pola + BR in second line, third line plus, relapsed, and refractory patients. Based on results from this study, pola was recently granted breakthrough ther- apy designation by the US Food and Drug Administration and PRIME (PRIority MEdicines) designation by the European Medicines Agency for the treatment of people with relapsed or refractory DLBCL.

The study is the only head-to-head com- parison of a novel targeted agent against the standard therapy in this patient popula- tion that is ineligible for stem cell transplant, Laurie H. Sehn, MD, a Clinical Assistant Professor with the BC Cancer Agency and University of British Columbia in Vancouver, said during her presentation. DLBLC is the most common subtype of non-Hodgkin lymphoma and accounts for approximately 33% cases of the disease. DLBCL is an aggressive lymphoma and it is generally responsive to frontline treatment. Relapse is common, however, and will occur in about 40% of patients. For these patients, salvage therapy options are limited and survival is short. It is estimated that about 123,000 people around the world are diag- nosed with DLBCL every year. Pola, an anti-CD79b antibody drug con- jugate, targets CD79b+ cells in B-cell non-Hodgkin lymphoma. This study reports on the combined results for safety and efficacy from the randomized r/r folli- cular lymphoma (FL) and DLBCL cohorts of a phase Ib/II study (ClinicalTrials.gov NCT02257567). The primary objective is complete response rate by PET scan 6–8 weeks after end of treatment by IRC using modified Lugano criteria (this required PET score 1–3 and negative bone marrow if positive at screening).

" …the addition of pola to BR increased complete

response rates from 15% to 40% (P = .012) at the end of treatment, as measured by PET scan and assessed

by an independent review committee.

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