Sequential Therapy
Therapy with IMIDs®
IMIDs in Relapsed-
Refractory Multiple Myeloma Patients
Tommasina Guglielmelli1, Sara Bringhen2, Alfredo Berruti1, Francesca Gay2,
Federica Cavallo2 Vittorio Montefusco3 Mariella Genuardi2 Eugenio Piro4
Federica Cavallo2, Vittorio Montefusco3, Mariella Genuardi2, Eugenio Piro ,
Maria T. Petrucci5, Tommaso Caravita6, Massimo Offidani7, Paolo
Corradini3, Mario Boccadoro2, Giuseppe Saglio1, Antonio Palumbo2
1University of Turin and San Luigi Hospital, Orbassano; 2University of Turin and San Giovanni Battista
Hospital, Turin; 3Istituto Nazionale Tumori, Milan; 4Division of Hematology,
gy Catanzaro; 5University La
Sapienza, Rome; 6University Tor-Vergata, Rome; 7Ematologia, Polo Ospedaliero Universitario, Ospedali
Riuniti di Ancona, Ancona; Italy
Disclosures
· TG, SB, MTP, TC, MO, PC, and AP have received honoraria from
Janssen Cilag and Celgene.
· FC has received honoraria from Celgene.
· MB has received honoraria from Janssen Cilag, Celgene, and
Novartis.
· GS has received honoraria from Celgene,
g
Novartis, and Bristol-
Myers Squibb.
· AB, FG, VM, MG, and EP have no conflicts of interest to disclose.
BACKGROUND
·
Lenalidomide is structurally related to thalidomide and was designed
to overcome some of the adverse events of
of thalidomide
thalidomide and provide
more potent inhibition of tumor necrosis factor-alpha.
·
Lenalidomide remains active in patients with multiple myeloma (MM)
who have previously been treated with thalidomide.1,2
who have previously been treated with thalidomide.
·
At present, no data are available on the efficacy of thalidomide in
patients previously exposed to lenalidomide.
OBJECTIVE
·
To evaluate the efficacy of the sequential use of lenalidomide and
thalidomide in patients with relapsed and refractory MM.
METHODS
Patients who received lenalidomide
·
A total of 118 MM patients received lenalidomide treatment and were
categorized as follows:
patients with no previous thalidomide exposure (T0) (n = 24)
thalidomide-sensitive patients (TS) (n = 20) (at least a PR during
thalidomide exposure)
thalidomide-resi t
s
t
an pati
tients (TR) (n = 74) (progressive disease during
thalidomide treatment post response)
·
10 patients in T0 group received Melphalan, Prednisone and Lenalidomide
(MPR)
() at diagnosis while all other patients received lenalidomide-
dexamethasone as salvage therapy (Table 1).
·
The median prior lines of therapy in T0, TS, and TR groups were 1 (range 0
3), 2 (range 15), and 3 (range 16), respectively.
Patients who received thalidomide
·
16 patients received thalidomide-dexamethasone treatment during
lenalidomide exposure (TD g
(group)
12 patients received MPR at diagnosis, 3 and 1 patients lenalidomide-
dexametasone, lenalidomide-doxorubicin-dexametasone at relapse
·
All patients had progressive disease during lenalidomide treatment.
METHODS
Outcome measures
·
Response to treatment was assessed according to International
Myeloma Working
Working Group (IWG) uniform response criteria
criteria with
with the
the
addition of minimal response 3
Dex, dexamethasone; Len, lenalidomide; Thal, thalidomide.
RESULTS
T0= no thal
TS=thal sensitive
TR=thal resistant
CR, complete response; ORR, overall response rate; OS, overall survival; NR, not
reached; TTP, time to progression.
· The response rates in 16 patients treated with lenalidomide first and
then with th
thalidomide-dt
dexame h
thasone are describ
ib d
e in T b
a l
ble 3.
· Median TTP and OS was similar in TR versus TD patients (P = 0.5
and P = 0.9, respectively).
PR, partial response; MR, minimal response; NR, no response
No previous thalidomide
P=0.03
Thalidomide sensitive
P=0.0001
P=0.01
Thalidomide resistant
No previous thalidomide
Thalidomide sensitive
P=0.02
Thalidomide resistant
P=0.5
P=0.9
CONCLUSIONS
·
Therefore, thalidomide following lenalidomide may be an
appropriate treatment option for
for patients with
with relapsed/refractory
relapsed/refractory
MM.
·
TTP was similar in thalidomide-resistant patients treated with
lenalidomide and lenalidomide-resistant patients treated
treated with
thalidomide: 7 months.
·
In patients with relapsed-refractory MM, the efficacy of lenalidomide
following thalidomide treatment,
treatment, and thalidomide following
following
lenalidomide treatment is similar.
References
1. Dimopoulos M, et al. N Engl J Med. 2007;357:2123-32.
2. Weber
Weber DM, et al. N Engl
Engl J Med
Med. 2007;357:2133-42.
3. Durie BG, et al. Leukemia. 2006;20:1467-73.
Presented at the 51st meeting of the American Society of Hematology, New Orleans, LA, USA,
December 58, 2009.
Acknowledgments
The authors received editorial support from Celgene Corporation.