POLATUZUMAB VEDOTIN PLUS BENDAMUSTINE AND RITUXIMAB OR OBINUTUZUMAB IN RELAPSED/REFRACTORY FOLLICULAR LYMPHOMA OR DIFFUSE LARGE B-CELL LYMPHOMA: UPDATED RESULTS OF A PHASE 1B/2 STUDY
Author(s): ,
Matthew Matasar
Affiliations:
Memorial Sloan Kettering Cancer Center,New York,United States
,
Alex F. Herrera
Affiliations:
City of Hope,Duarte,United States
,
Manali Kamdar
Affiliations:
University of Colorado,Denver,United States
,
Amitkumar Mehta
Affiliations:
Department of Medicine,University of Birmingham,Birmingham,United States
,
Sarit Assouline
Affiliations:
Jewish General Hospital,Montreal,Canada
,
Isabelle Fleury
Affiliations:
Department of Hematology,Maisonneuve-Rosemont Hospital and University of Montreal,Montreal,Canada
,
Tae Min Kim
Affiliations:
Seoul National University Hospital,Seoul,Korea, Republic Of
,
Won Seog Kim
Affiliations:
Samsung Medical Center,Seoul,Korea, Republic Of
,
Francesc Bosch
Affiliations:
Hospital Universitari Vall d'Hebron,Barcelona,Spain
,
John Radford
Affiliations:
Manchester Academic Health Science Centre,The University of Manchester and the Christie NHS Foundation Trust,Manchester,United Kingdom
,
Christopher R. Flowers
Affiliations:
Winship Cancer Institute of Emory University,Atlanta,United States
,
Lilian Bu
Affiliations:
Roche,Shanghai,China
,
Wan-Jen Hong
Affiliations:
Genentech, Inc.,South San Francisco,United States
Laurie H. Sehn
Affiliations:
BC Cancer Agency,Vancouver,Canada
EHA Library. Matasar M. Jun 24, 2017; 181755; S468
Matthew Matasar
Matthew Matasar
Contributions
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Abstract

Abstract: S468

Type: Oral Presentation

Presentation during EHA22: On Saturday, June 24, 2017 from 16:30 - 16:45

Location: Hall C

Background

Transplant ineligible patients (pts) with relapsed/refractory (R/R) FL or DLBCL have poor outcomes.  Polatuzumab vedotin (pola) is an antibody drug conjugate that targets delivery of the microtubule inhibitor MMAE to cells expressing CD79b.  Pola + rituximab (R) previously showed promising responses in R/R FL and DLBCL.  Adding bendamustine (B) to pola-R and substituting obinutuzumab (G) for R could improve outcomes. We report updated results from the Phase 1b/2 (P1b/2) study evaluating pola + BR or BG in R/R FL and DLBCL and the expansion cohorts evaluating pola + BG in R/R FL and DLBCL (ClinicalTrials.gov NCT02257567).

Aims

The primary aim is to assess safety and tolerability of pola + BR/BG in R/R FL and DLBCL. Secondary aims include assessing safety and efficacy of pola + BG in an expansion cohort.

Methods
All pts provided informed consent to participate in the study and were treated with pola (1.8 mg/kg) + B (90 mg/m2) and R (375 mg/m2) or G (1000 mg) every 28 days (FL) or 21 days (DLBCL) for 6 cycles. Responses were assessed by modified Lugano 2014 criteria after 3 cycles, end of treatment (tx), and every 6 months for 2 years during follow-up (fu).

Results

As of 14 Nov 2016, 65 pts were enrolled: 24 pts (12 FL, 12 DLBCL) in P1b and 41 pts (20 FL and 21 DLBCL) in P2.  In safety evaluable pts, FL pts (N=32) were median age of 63 yr (37-86), 82% ECOG 0-1 and 6% ECOG 2, 44% FLIPI1 3-5, 78% Stage III/IV,  2 (1-7) median lines of prior tx, 38% refractory to last tx, 13% prior transplant (BMT). DLBCL pts (N=32) were median age 66 (30-86), 88% ECOG 0-1 and 13% ECOG 2, 59% IPI 3-5, 75% Stage III/IV, 2 (1-7) median lines of prior tx, 82% refractory to last tx, 3% prior BMT.
Among 64 pts who received ≥1 dose, the adverse events (AEs) that occurred in >20% of pts were: fatigue (67%), nausea (54%), diarrhea (54%), vomiting (42%), pyrexia (39%) and constipation (39%).  As expected, grade (Gr) 3/4 cytopenias were common: neutropenia (34% FL, 28% DLBCL), thrombcytopenia (16% FL, 13% DLBCL), anemia (6% FL, 9% DLBCL). Tx emergent neuropathy occurred in 19/64 (30%) of pts, with 1 Gr 3 event, and led to pola discontinuation in 1 pt, dose reduction in 2 pts, and interruption in 1 pt.
In FL, 75% (24/32) had Gr 3/4 AEs and 41% (13/32) had serious AEs (SAEs). The only SAE occurring in ≥10% was infection (22%). The most common Gr 3/4 non-heme AEs were infection (16%) and hypokalemia (9%). AEs led to study tx discontinuation in 6 pts. B was stopped in 2 pts due to Gr 3 thromboctyopenia.  Of 4 deaths: 2 were PD and 2 were Gr 5 AEs, 1 tx related (PML), 1 tx unrelated. In DLBCL, 88% (28/32) had Gr 3/4 AEs and 63% (20/32) had SAEs.  Most common Gr 3/4 non-heme AEs were febrile neutropenia (13%), fatigue (13%), and diarrhea (13%).  SAEs occurring in ≥10% of pts were infection (33%) and pyrexia (22%).  AEs led to study tx interruption in 19 pts and discontinuation in 8 pts.  There were 13 deaths: 9 PD, 4 AE (all unrelated to tx).
Responses by modified Lugano 2014 criteria are shown in Table1.
Median duration of response (DoR) for FL P1b pts was 16 months (mo)(median fu 14.5 mo). Median DoR for FL P2 (median fu 6.5 mo) and DLBCL P1b/2 (median fu 13.7 mo P1b, 6.4 mo P2) have not been reached.

Conclusion
Updated evaluation of pola + BR shows promising durable responses and an acceptable safety profile in heavily pre-treated R/R FL and DLBCL pts. Safety and efficacy data will be updated at the time of presentation.

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

Keyword(s): Targeted therapy, Relapsed lymphoma, Obinutuzumab, Non-Hodgkin's lymphoma

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