POLA‐R‐CHP: POLATUZUMAB VEDOTIN COMBINED WITH RITUXIMAB, CYCLOPHOSPHAMIDE, DOXORUBICIN, PREDNISONE FOR PATIENTS WITH PREVIOUSLY UNTREATED DIFFUSE LARGE B‐CELL LYMPHOMA

Abstract

Introduction: Polatuzumab vedotin (pola) is an antibody drug conjugate containing the anti-mitotic MMAE targeting CD79b, an antigen expressed ubiquitously in DLBCL. Pola as monotherapy and in combination with anti-CD20 antibodies demonstrated encouraging efficacy in r/r DLBCL (Palanca-Wessels, 2015; Morschhauser, 2014). The initial dose-escalation portion of this multicenter, open-label Ph Ib/II study of pola in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (pola-R-CHP) showed an acceptable safety profile and established a recommended Ph II dose of pola at 1.8 mg/kg (Bartlett, 2015). We report updated safety and efficacy results for the Ph II dose in 45 previously untreated DLBCL patients (pts) (ClinicalTrials.gov NCT01992653). Methods: Five pts of the dose escalation phase and the 40 pts of the expansion phase were included in this analysis. All had newly diagnosed DLBCL and were treated with pola at 1.8 mg/kg and R-CHP at standard doses every 21 days for 6 or 8 cycles. Investigator assessments for anti-tumor activity were performed according to IWG 2007 following 4 cycles and at the end of study treatment (EOT). Results: All 45 pts received at least one dose of study drug. The median age was 69 years; 93% were >60 years, 33% ECOG >1, 82% Stage III/IV, and 78% IPI 3-5. Of the 29 pts with cell of origin (COO) status by digital gene expression, 11 (38%) were ABC, 14 (48%) were GCB, while 4 (14%) were unclassified. Forty patients completed 6 or 8 cycles (23 and 17 pts respectively). All pts experienced at least one AE. Grade (Gr) 3/4 AEs occurred in 58%, and one pt experienced a Gr 5 atrial fibrillation. Gr 3/4 neutropenia and febrile neutropenia (FN) occurred in 27% and 11%. Serious adverse events (SAEs) were reported in 17 pts (38%) including 3 FN, and 2 each of neutropenia, pneumonia, pulmonary embolism and influenza A. Peripheral neuropathy (PN) occurred in 18 (40%) patients. Among these pts with PN, 12 were Gr 1, 4 were Gr 2, and 2 were Gr 3. All Gr 2/3 PN attributed to pola occurred at C5 or later. Four pts discontinued pola early for the following reasons: Gr 5 atrial fibrillation (after C2, not attributed to pola by investigator), E. coli UTI (C5), worsening essential tremor (C3), PN (C7). During treatment, 6 pts had dose reductions in pola and 1 pt had cyclophosphamide and doxorubicin dose reductions. ORR by PET at EOT was 91%; 78% had a CR and 13% PR. 3 pts progressed and 1 was unevaluable. In the COO determined population, CR was 91% in ABC and 86% in GCB pts. At the data cutoff of November 4, 2016 with a median study duration of 9.5 months, (range 1.3-28 months), only 1 pt had a disease progression in follow up. Conclusions: Pola at 1.8 mg/kg in combination with R-CHP in 1 L DLBCL has an acceptable safety profile and produced promising response rates at the end of treatment. The majority of the patients in this trial represented a poor prognosis group by age and IPI. In this context, treatment response to this regimen may warrant further exploration. Keywords: antibody-dependent cytotoxicity (ADC); diffuse large B-cell lymphoma (DLBCL); non-Hodgkin lymphoma (NHL).