POST HOC ANALYSIS OF THE AUGMENT PHASE III RANDOMIZED STUDY OF LENALIDOMIDE PLUS RITUXIMAB (R2) VS RITUXIMAB/PLACEBO IN PATIENTS WITH RELAPSED/REFRACTORY MARGINAL ZONE LYMPHOMA
Author(s): ,
Catherine Thieblemont
Affiliations:
Hemato-Oncology, APHP, Hôpital Saint-Louis,Paris,France;Descartes University,Paris,France;Diderot University, Sorbonne Paris-Cité,Paris,France
,
John P. Leonard
Affiliations:
Meyer Cancer Center, Weill Cornell Medicine and New York Presbyterian Hospital,New York,United States
,
Marek Trneny
Affiliations:
Charles University, General Hospital,Prague,Czech Republic
,
Koji Izutsu
Affiliations:
National Cancer Center Hospital,Tokyo,Japan
,
Nathan H. Fowler
Affiliations:
University of Texas MD Anderson Cancer Center,Houston,United States
,
Xiaonan Hong
Affiliations:
Fudan University Shanghai Cancer Center,Shanghai,China
,
Huilai Zhang
Affiliations:
Tianjin Medical University Cancer Institute and Hospital,Tianjin,China
,
Fritz Offner
Affiliations:
UZ Gent,Gent,Belgium
,
Adriana Scheliga
Affiliations:
INCA Instituto Nacional De Câncer, Rio de Janeiro,Brazil
,
Grzegorz Nowakowski
Affiliations:
Mayo Clinic,Rochester,United States
,
Antonio Pinto
Affiliations:
Istituto Nazionale Tumori, Fondazione ‘G. Pascale’, IRCCS,Naples,Italy
,
Francesca Re
Affiliations:
Azienda Ospedaliero Universitaria di Parma, Parma,Italy
,
Laura Maria Fogliatto
Affiliations:
Hospital de Clinicas de Porto Alegre,Porto Alegre,Brazil
,
Phillip Scheinberg
Affiliations:
Hospital A Beneficência Portuguesa de São Paulo,São Paulo,Brazil
,
Ian Flinn
Affiliations:
Sarah Cannon Research Institute/Tennessee Oncology,Nashville,United States
,
Claudia Moreira
Affiliations:
Instituto Português de Oncologia Do Porto Francisco Gentil Epe,Porto,Portugal
,
Myron Czuczman
Affiliations:
Celgene Corporation,Summit,United States
,
Stacey A. Kalambakas
Affiliations:
Celgene Corporation,Summit,United States
,
Pierre Fustier
Affiliations:
Celgene Corporation,Boudry,Switzerland
,
Chengqing Wu
Affiliations:
Celgene Corporation,Summit,United States
John Gribben
Affiliations:
Centre for Haemato-Oncology, Barts Cancer Institute,London,United Kingdom
EHA Library. Thieblemont C. Jun 15, 2019; 266879; PS1262
Catherine Thieblemont
Catherine Thieblemont
Contributions
Abstract

Abstract: PS1262

Type: Poster Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 17:30 - 19:00

Location: Poster area

Background
Lenalidomide plus rituximab (R2) has established efficacy and a tolerable safety profile in patients with previously untreated and relapsed/refractory (R/R) indolent NHL. This includes patients with marginal zone lymphoma (MZL) who are generally treated in a similar manner to follicular lymphoma (FL).

Aims
Primary results for the AUGMENT study in R/R FL grade 1-3a and MZL showed significantly improved progression-free survival (PFS) for R2 over R/placebo in the overall population and in the subgroup analyses, with the exception of the MZL subgroup. Given the small sample size for MZL patients, post hoc analyses of baseline characteristics and univariate/multivariate analyses of PFS were conducted to examine possible explanations for these results.

Methods
The phase III AUGMENT study randomized patients 1:1 to R2 (lenalidomide PO 20 mg/day (d), d1-21/28 X12 cycles plus rituximab IV 375 mg/m2 weekly in cycle 1 and d1 of cycles 2-5) or rituximab-placebo (R/placebo; same dosing schedule). PFS by 2007 IWG (without PET) was the primary endpoint. Post hoc Cox regression models were used for univariate analysis of one risk factor and multivariate analyses including treatment arm and significant risk factors (P<0.05) from the univariate analyses.

Results
A total of 63/358 (18%) MZL patients were part of the overall study population, including n=14/16 MALT, n=9/6 splenic, and n=8/10 nodal MZL subtypes for respective R2 and R/placebo arms. Numerical differences between treatment arms for baseline demographics and disease characteristics for MZL patients favoring the R/placebo arm were: fewer R2 patients had an ECOG score of 0 (55% R2 vs 72% R/placebo), and more R2 (vs R/placebo) patients were older (≥65 y: 68% vs 59%; ≥70 y: 42% vs 38%), were refractory to the last prior regimen (13% vs 3%), had Ann Arbor stage IV disease at enrollment (65% vs 41%), high-risk MALT-IPI score (50% vs 19%), elevated LDH (29% vs 19%), B symptoms (13% vs 3%), and high tumor burden per GELF criteria (65% vs 56%). The most common grade 3/4 AEs for MZL patients receiving R2 vs R/placebo, respectively, were neutropenia (47% vs 16%), pneumonia (3% vs 13%), and leukopenia (10% vs 0). A total of 5 deaths occurred in the R2 arm (most associated with progression of disease; 2 deaths occurred early at 3 and 13 days after randomization [one prior to receiving R2 and one 2 days after treatment initiation]) and 2 in the R/placebo arm. Despite worse prognostic features, best response was improved with R2 (vs R/placebo) with ORR=65% vs 44% (P=0.13) and CR=29% vs 13% (P=0.13), although neither were statistically significant. Improved response rates did not translate into a survival advantage for R2. Median PFS for MZL patients was 20.2 mo R2 vs 25.2 mo R/placebo (HR=1.00; 95% CI, 0.47-2.13; P=1.0). Univariate analyses showed that several baseline factors were prognostic for MZL patients (P<0.05): Ann Arbor stage IV, elevated LDH, and unfit for chemotherapy (Table). Multivariate analyses adjusting for the imbalance in these 3 significant prognostic factors showed an adjusted PFS HR of 0.51 (95% CI, 0.20-1.28) favoring the R2 arm, similar to the PFS HR in the overall population (HR=0.46; 95% CI, 0.34-0.63). The univariate and multivariate analyses suggested that the imbalance in baseline prognostic factors impacted PFS results for MZL patients.

Conclusion
Overall, these findings suggest that the PFS results in MZL patients were negatively impacted by the imbalance in baseline prognostic factors and more aggressive disease in the R2 over the R/placebo arm.

Session topic: 18. Indolent and mantle-cell non-Hodgkin lymphoma - Clinical

Keyword(s): Imids, Marginal zone, Rituximab

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