ADDING POLATUZUMAB VEDOTIN (POLA) TO BENDAMUSTINE AND RITUXIMAB (BR) TREATMENT IMPROVES SURVIVAL IN PATIENTS WITH RELAPSED/REFRACTORY DLBCL: RESULTS OF A PHASE 2 CLINICAL TRIAL
Author(s): ,
Laurie H. Sehn
Affiliations:
BC Cancer Agency,Vancouver,Canada
,
Manali Kamdar
Affiliations:
University of Colorado,Denver,United States
,
Alex F. Herrera
Affiliations:
City of Hope,Duarte,United States
,
Andrew McMillan
Affiliations:
Nottingham University Hospitals,Nottingham,United Kingdom
,
Christopher Flowers
Affiliations:
Winship Cancer Institute of Emory University,Atlanta,United States
,
Won Seog Kim
Affiliations:
Samsung Medical Center,Seoul,Korea, Republic Of
,
Tae Min Kim
Affiliations:
Seoul National University Hospital,Seoul,Korea, Republic Of
,
Muhit Özcan
Affiliations:
Ankara University,Ankara,Turkey
,
Marek Trněný
Affiliations:
Charles University,Prague,Czech Republic
,
Judit Demeter
Affiliations:
Semmelweis University,Budapest,Hungary
,
Mark Hertzberg
Affiliations:
Prince of Wales Hospital,Sydney,Australia
,
Gilles Salles
Affiliations:
Hospices Civils de Lyon,Université Lyon-1,Lyon,France
,
Andrew Davies
Affiliations:
Cancer Research UK Centre, Cancer Sciences Division,University of Southampton,Southampton,United Kingdom
,
Jamie Hirata
Affiliations:
Genentech, Inc.,South San Francisco,United States
,
Ji Cheng
Affiliations:
Hoffmann-La Roche,Mississauga,Canada
,
Grace Ku
Affiliations:
Genentech, Inc.,South San Francisco,United States
Matthew J. Matasar
Affiliations:
Memorial Sloan Kettering Cancer Center,New York,United States
EHA Library. Sehn L. 06/16/18; 214489; S802
Laurie Sehn
Laurie Sehn
Contributions
Abstract

Abstract: S802

Type: Oral Presentation

Presentation during EHA23: On Saturday, June 16, 2018 from 12:15 - 12:30

Location: Room A1

Background
Pola is an antibody-drug conjugate targeting CD79b+ cells in B-NHL. Early results led to FDA breakthrough therapy status and EMA PRIME designation. We now report combined results for safety and efficacy from the randomized r/r FL and DLBCL cohorts of a phase 1b/2 study (ClinicalTrials.gov NCT02257567).

Aims
The primary objective is complete response rate by PET scan (PET-CR) 6-8 weeks after end of treatment by independent review committee (IRC) using modified Lugano criteria (PET-CR required PET score 1-3 and negative bone marrow if positive at screening).

Methods
After informed consent was obtained, 80 FL and 80 DLBCL transplant-ineligible patients (pts) were randomized 1:1 to pola 1.8 mg/kg + BR (B: 90mg/m2 x 2 days; R: 375mg/m2) or BR for 6 cycles (q28 days FL, q21 days DLBCL). Pts were stratified by duration of response to last treatment ≤12 mo or >12 mo. FL pts were also stratified by high vs low disease burden.

Results
For FL pts (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 24 Oct 17, median follow up was 15 months. DLBCL characteristics and follow up were previously described (Sehn, ASH 2017). Safety: The most common grade 3–5 adverse events (AEs) that were higher in pola+BR vs BR in both FL and DLBCL were cytopenias, febrile neutropenia, and infections. Serious AEs higher in pola+BR vs BR were febrile neutropenia (FL, DLBCL) and infection (FL).  Grade 5 AE rates were similar between treatment arms per histology: 5% (FL) and 18% (DLBCL). Efficacy: PET-CR by IRC and progression-free survival (PFS) by investigator (INV) were similar between FL arms (Figure A). In DLBCL, pola+BR showed significantly higher IRC-PET-CR rates (p=0.012) and longer median (m) INV-PFS (p<0.0001) and overall survival (mOS; p=0.0008) (Figure A,B,C). Also in DLBCL, longer PFS and OS were seen for pola+BR in 2nd-line (2L), 3rd-line plus (3L+), relapsed, and refractory pts. mPFS (pola+BR vs BR in months): 2L (11.1 vs 3.7), 3L+ (6.0 vs 2.0), relapsed (11.1 vs 5.1), refractory (6.0 vs 1.9). mOS: 2L (not reached [NR] vs 5.9), 3L+ (11.5 vs 3.8), relapsed (NR, NR), refractory (11.5 vs 3.8).

Conclusion
The toxicity of pola+BR was manageable and as expected. In FL, pola+BR showed similar PET-CR rate compared to BR. Time-to-event endpoints are immature at this time due to low event rate.  In contrast, in DLBCL, pola+BR led to significantly higher PET-CR rate and notably longer PFS and OS compared to BR regardless of prior treatment status.

Session topic: 21. Aggressive Non-Hodgkin lymphoma - Clinical

Keyword(s): Diffuse large B cell lymphoma, Follicular lymphoma, Immunoconjugate, Phase II

Abstract: S802

Type: Oral Presentation

Presentation during EHA23: On Saturday, June 16, 2018 from 12:15 - 12:30

Location: Room A1

Background
Pola is an antibody-drug conjugate targeting CD79b+ cells in B-NHL. Early results led to FDA breakthrough therapy status and EMA PRIME designation. We now report combined results for safety and efficacy from the randomized r/r FL and DLBCL cohorts of a phase 1b/2 study (ClinicalTrials.gov NCT02257567).

Aims
The primary objective is complete response rate by PET scan (PET-CR) 6-8 weeks after end of treatment by independent review committee (IRC) using modified Lugano criteria (PET-CR required PET score 1-3 and negative bone marrow if positive at screening).

Methods
After informed consent was obtained, 80 FL and 80 DLBCL transplant-ineligible patients (pts) were randomized 1:1 to pola 1.8 mg/kg + BR (B: 90mg/m2 x 2 days; R: 375mg/m2) or BR for 6 cycles (q28 days FL, q21 days DLBCL). Pts were stratified by duration of response to last treatment ≤12 mo or >12 mo. FL pts were also stratified by high vs low disease burden.

Results
For FL pts (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 24 Oct 17, median follow up was 15 months. DLBCL characteristics and follow up were previously described (Sehn, ASH 2017). Safety: The most common grade 3–5 adverse events (AEs) that were higher in pola+BR vs BR in both FL and DLBCL were cytopenias, febrile neutropenia, and infections. Serious AEs higher in pola+BR vs BR were febrile neutropenia (FL, DLBCL) and infection (FL).  Grade 5 AE rates were similar between treatment arms per histology: 5% (FL) and 18% (DLBCL). Efficacy: PET-CR by IRC and progression-free survival (PFS) by investigator (INV) were similar between FL arms (Figure A). In DLBCL, pola+BR showed significantly higher IRC-PET-CR rates (p=0.012) and longer median (m) INV-PFS (p<0.0001) and overall survival (mOS; p=0.0008) (Figure A,B,C). Also in DLBCL, longer PFS and OS were seen for pola+BR in 2nd-line (2L), 3rd-line plus (3L+), relapsed, and refractory pts. mPFS (pola+BR vs BR in months): 2L (11.1 vs 3.7), 3L+ (6.0 vs 2.0), relapsed (11.1 vs 5.1), refractory (6.0 vs 1.9). mOS: 2L (not reached [NR] vs 5.9), 3L+ (11.5 vs 3.8), relapsed (NR, NR), refractory (11.5 vs 3.8).

Conclusion
The toxicity of pola+BR was manageable and as expected. In FL, pola+BR showed similar PET-CR rate compared to BR. Time-to-event endpoints are immature at this time due to low event rate.  In contrast, in DLBCL, pola+BR led to significantly higher PET-CR rate and notably longer PFS and OS compared to BR regardless of prior treatment status.

Session topic: 21. Aggressive Non-Hodgkin lymphoma - Clinical

Keyword(s): Diffuse large B cell lymphoma, Follicular lymphoma, Immunoconjugate, Phase II

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