EHA Library - The official digital education library of European Hematology Association (EHA)

POLA-R-CHP: POLATUZUMAB VEDOTIN COMBINED WITH RITUXIMAB, CYCLOPHOSPHAMIDE, DOXORUBICIN, PREDNISONE FOR PATIENTS WITH PREVIOUSLY UNTREATED DIFFUSE LARGE B-CELL LYMPHOMA
Author(s): ,
Hervé Tilly
Affiliations:
Centre Henri Becquerel,University of Rouen,Rouen,France
,
Jeff Sharman
Affiliations:
Willamette Valley Cancer Institute,Springfield,United States;US Oncology Research,The Woodlands,United States
,
Nancy Bartlett
Affiliations:
Siteman Cancer Center,Washington University School of Medicine,St Louis,United States
,
Franck Morschhauser
Affiliations:
University Hospital of Lille,Lille,France
,
Corinne Haioun
Affiliations:
Henri Mondor University Hospital,Creteil,France
,
Javier Munoz
Affiliations:
Banner MD Anderson Cancer Center,Gilbert,United States
,
Andy Chen
Affiliations:
Oregon Health and Science University,Portland,United States
,
Thierry Lamy
Affiliations:
Hematology Department,INSERM U917 / University Hospital of Rennes,Rennes,France
,
Lijia Wang
Affiliations:
Genentech, Inc.,South San Francisco,United States
,
Elicia Penuel
Affiliations:
Genentech, Inc.,South San Francisco,United States
,
Jamie Hirata
Affiliations:
Genentech, Inc.,South San Francisco,United States
,
Calvin Lee
Affiliations:
Genentech, Inc.,South San Francisco,United States
Gilles Salles
Affiliations:
South Lyon Hospital Complex,Lyon,France
(Abstract release date: 05/18/17) EHA Library. Tilly H. 06/23/17; 181393; S106
H Tilly
H Tilly
Contributions
Abstract

Abstract: S106

Type: Oral Presentation

Presentation during EHA22: On Friday, June 23, 2017 from 11:45 - 12:00

Location: Hall B

Background
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.1,2 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.3 We report updated safety and efficacy results for the Ph II dose in 45 previously untreated DLBCL patients (pts) (ClinicalTrials.gov NCT01992653).

Aims
To evaluate the safety and efficacy of pola-R-CHP as first-line treatment in patients with DLBCL.

Methods
Five pts of the dose escalation phase and the 40 pts of the expansion phase were included in this analysis. All pts provided informed consent to participate in the study. 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. 

Conclusion

Pola at 1.8 mg/kg in combination with R-CHP in 1L 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.
1. Palanca-Wessels MCA, et al. Lancet Oncol 2015; 16:704-15
2. Morschhauser F, et al. Blood 2014; 124:4457
3. Bartlett N, et al. Blood 2015; 126:2726 

Session topic: 20. Aggressive Non-Hodgkin lymphoma - Clinical

Keyword(s): Targeted therapy, Phase II, DLBCL, Antibody targeting

Abstract: S106

Type: Oral Presentation

Presentation during EHA22: On Friday, June 23, 2017 from 11:45 - 12:00

Location: Hall B

Background
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.1,2 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.3 We report updated safety and efficacy results for the Ph II dose in 45 previously untreated DLBCL patients (pts) (ClinicalTrials.gov NCT01992653).

Aims
To evaluate the safety and efficacy of pola-R-CHP as first-line treatment in patients with DLBCL.

Methods
Five pts of the dose escalation phase and the 40 pts of the expansion phase were included in this analysis. All pts provided informed consent to participate in the study. 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. 

Conclusion

Pola at 1.8 mg/kg in combination with R-CHP in 1L 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.
1. Palanca-Wessels MCA, et al. Lancet Oncol 2015; 16:704-15
2. Morschhauser F, et al. Blood 2014; 124:4457
3. Bartlett N, et al. Blood 2015; 126:2726 

Session topic: 20. Aggressive Non-Hodgkin lymphoma - Clinical

Keyword(s): Targeted therapy, Phase II, DLBCL, Antibody targeting

By clicking “Accept Terms & all Cookies” or by continuing to browse, you agree to the storing of third-party cookies on your device to enhance your user experience and agree to the user terms and conditions of this learning management system (LMS).

Cookie Settings
Accept Terms & all Cookies