LENALIDOMIDE IN RELAPSED OR REFRACTORY DIFFUSE LARGE B CELL LYMPHOMA: IS IT A VALID TREATMENT OPTION?
Author(s): ,
Patrizia Mondello
Affiliations:
Human Pathology,University of Messina,Messina,Italy
,
Normann Steiner
Affiliations:
Internal Medicine V
,
Wolfgang Willenbacher
Affiliations:
Internal Medicine V
,
Simone Ferrero
Affiliations:
Molecular Biotechnologies and Health Sciences,University of Torino,Torino,Italy
,
Alessandra Marabese
Affiliations:
Hematology & CBMT,Ospedale di Bolzano,Bolzano,Italy
,
Vincenzo Pitini
Affiliations:
Human Pathology,University of Messina,Messina,Italy
,
Salvatore Cuzzocrea
Affiliations:
Chemical, Biological, Pharmaceutical and Environmental Sciences,University of Messina,Messina,Italy
Michael Mian
Affiliations:
Hematology & CBMT,Ospedale di Bolzano,Bolzano,Italy
EHA Learning Center. Mondello P. Jun 11, 2016; 133584
Dr. Patrizia Mondello
Dr. Patrizia Mondello
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Abstract
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Abstract: P696

Type: Poster Presentation

Presentation during EHA21: On Saturday, June 11, 2016 from 17:30 - 19:00

Location: Poster area (Hall H)

Background
Diffuse large B cell lymphoma (DLBCL) is the most frequent aggressive non-Hodgkin lymphoma (NHL) in the western country. Despite its typical morphology, DLBCL is characterized by molecular heterogeneity, which can be classified by gene expression profiling (GEP) in two main subgroups based on the cell of origin, namely germinal center B cell (GCB) and activated B-cell. However, GEP is not routinely performed, which is why immunohistochemistry (IHC) is commonly used for designating these two subtypes. Because of the addiction to different oncogenic driver pathways, each subtype differs in response to drugs, leading to a distinct prognosis. In particular, the cure rate of ABC is only 40% after standard immunochemotherapy, hence novel therapeutic approaches are urgently needed. Prospective randomized studies regarding the use of lenalidomide in relapsed/refractory (R/R) DLBCL have demonstrated efficacy and feasibility of this immunomodulatory agent.

Aims
Up to now, data evaluating this drug in clinical practice are lacking. Therefore, we assessed its toxicity and efficacy in the largest R/R DLBCL real-life cohort carried out up to now.

Methods
From January 2006 to January 2015, 123 consecutive patients affected by R/R DLBCL who underwent lenalidomide monotherapy were retrospectively assessed in 3 European cancer centers.

Results
All patients received a starting dose of either 15 mg/day or 25 mg/day of lenalidomide. Response to treatment differed significantly between the two IHC subgroups:  patients with non-GCB DLBCL achieved a complete remission (CR) in 32% and a partial remission (PR) in 33% compared to 0% and 3% in the GCB group (p< 0.0001 and p=0.001). Toxicity was limited and reversible. The median follow-up was 4.5 years (range 2-108 months). The median duration of response was 4 months (range 1-10 months) and 15 months (5-23 months) in GCB and non-GCB DLBCL, respectively (p< 0.001). Patients receiving the 25 mg daily of lenalidomide had an overall superior outcome compared to those who underwent the 15 mg regimen, namely 21% achieved a CR and 23% a PR compared to 0% and 8% (p=0.007 and 0.05). Also median duration of response varied significantly between both dosing groups (10 vs 4 months; p=0.03). Overall, the median progression free survival was 34 months (range 2-108 months), ranging between 37 and 30 months according to the non-GCB and GCB DLBCL group (p< 0.0001) and between 24 and 34 months (p=0.002) according to the higher or lower lenalidomide dosing. However, overall survival was similar between the different subgroups (38 vs 41 months in non-GCB and GCB DLBCL, p=0.2; 38 vs 42 months in 15 and 25 mg/die, p= 0.4). 

Conclusion
In this real-life setting, we demonstrated that lenalidomide is a valid treatment option for R/R DLBCL with only limited and reversible toxicity. As expected, lenalidomide is more efficient in patients with non-GCB DLBCL, but responses were also observed in the other subgroup, which is why it can be considered also for GCB DLBCL. If clinically feasible, the 25mg dosing should be preferred.

Session topic: Aggressive Non-Hodgkin lymphoma - Clinical

Keyword(s): Diffuse large B cell lymphoma, Immunomodulatory thalidomide analog, Immunotherapy, Relapsed lymphoma
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