Sequential Therapy with IMID's in Relapsed-Refractory Multiple Myeloma Patients.
Authors: Guglielmelli Tommasina , Bringhen Sara , Berruti Alfredo , Gay Francesca , Cavallo Federica , Montefusco Vittorio , Genuardi Mariella , Piro Eugenio , Petrucci Maria Teresa , Caravita Tommaso , Offidani Massimo , Corradini Paolo , Boccadoro Mario , Saglio Giuseppe , Palumbo Antonio 
Published: October 2019

Abstract
Abstract 2888
Poster Board II-864

Introduction.
Lenalidomide is a thalidomide derivative with improved efficacy. Lenalidomide remains active in multiple myeloma (MM) patients despite previous thalidomide treatment. At present, no data are available on the efficacy of thalidomide in patients previously exposed to lenalidomide. The aim of this study is to evaluate the efficacy of the sequential use of these two drugs in relapsed-refractory MM patients.

Methods.
A total of 118 MM patients received lenalidomide treatment and were categorized as follows: 1) patients with no previous thalidomide exposure (T0) (n=24); 2) thalidomide sensitive patients (TS) (n=20) (at least a PR during thalidomide exposure); 3) thalidomide resistant patients (TR) (n=71) (progressive disease during thalidomide treatment). Ten patients in T0 group received MPR at diagnosis while all other patients received lenalidomide-dexametasone as salvage therapy. Median prior lines of therapy in T0, TS and TR groups was 1 (range 0-3), 2 (range 1-5) and 3 (range 1-6), respectively.
Fifteen patients received thalidomide-dexametasone treatment after lenalidomide exposure (12 patients received MPR at diagnosis and 3 patients lenalidomide-dexametasone at relapse). All patients had progressive disease during lenalidomide treatment. Response to treatment was assessed according to IMWG uniform response criteria with the addition of MR.

Results.
No statistical difference was found in the overall response rate (more than PR) between T0 and TS patients (83.3% vs 65%, p=0.18) and between TS and TR patients (65% vs 61.9%, p=0.8). Treatment with lenalidomide-dexametasone led to a significant improved overall response when compared T0 vs TR patients (83.3% vs 61.9%, p=0.04). Lenalidomide was significantly more effective in prolonging TTP in T0 with respect to TS and TR groups (median TTP not reached, P=0.0001) and also prolonged TTP in TS vs TR patients (median, 11 vs 7,5 months P=0.03). Median OS was not reached in T0 group after 48 months (P=0.09) and was similar in TS and TR groups (median 15 months, P=0.5).
In the 15 patients treated with lenalidomide first and then with thalidomide-dexametasone as salvage therapy, response rate was: 27% at least PR, 40% MR, 27% NR, 13% PD. Median TTP was 7 months (range 2-30) and median OS was not reached at 40 months.

Conclusion.
Lenalidomide is highly effective in MM patients thalidomide resistance. Thalidomide is already effective in MM patients pure resistance to lenalidomide. TTP was similar in both groups (7 months). Clinical efficacy of lenalidomide in relapsed-refractory myeloma patients already exposed to thalidomide is similar to the efficacy of thalidomide in patients already exposed to lenalidomide.

Disclosures:
Guglielmelli: Janssen Cilag: Honoraria; Celgene: Honoraria. Bringhen:Janssen Cilag: Honoraria; Celgene: Honoraria. Cavallo:Celgene: Honoraria. Petrucci:Celgene: Honoraria; Janssen Cilag: Honoraria. Caravita:Celgene: Honoraria; Janssen Cilag: Honoraria. Offidani:Celgene: Honoraria; Janssen Cilag: Honoraria. Corradini:Celgene: Honoraria; Janssen Cilag: Honoraria. Boccadoro:Janssen Cilag: Honoraria; Celgene: Honoraria; Novartis: Honoraria. Saglio:Celgene: Honoraria; Novartis: Honoraria; Bristol Myers: Honoraria. Palumbo:Celgene: Honoraria; Janssen Cilag: Honoraria.