TY - JOUR
TI - Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma
(IKEMA): a multicentre, open-label, randomised phase 3 trial
AU - Moreau, Philippe
AU - Dimopoulos, Meletios-Athanasios
AU - Mikhael, Joseph
AU - and Yong, Kwee
AU - Capra, Marcelo
AU - Facon, Thierry
AU - Hajek, Roman
AU - and Spicka, Ivan
AU - Baker, Ross
AU - Kim, Kihyun
AU - Martinez, Gracia
AU - and Min, Chang-Ki
AU - Pour, Ludek
AU - Leleu, Xavier
AU - Oriol, Albert
AU - and Koh, Youngil
AU - Suzuki, Kenshi
AU - Risse, Marie-Laure
AU - Asset,
AU - Gaelle
AU - Mace, Sandrine
AU - Martin, Thomas
AU - IKEMA Study Grp
JO - The Lancet Neurology
PY - 2021
VL - 397
TODO - 10292
SP - 2361-2371
PB - ELSEVIER SCIENCE INC 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN - null
TODO - 10.1016/S0140-6736(21)00592-4
TODO - null
TODO - Background Isatuximab is an anti-CD38 monoclonal antibody approved in
combination with pomalidomide-dexamethasone and
carfilzomib-dexamethasone for relapsed or refractory multiple myeloma.
This phase 3, openlabel study compared the efficacy of isatuximab plus
carfilzomib-dexamethasone versus carfilzomib-dexamethasone in patients
with relapsed multiple rnyeloma.
Methods This was a prospective, randomised, open-label, parallel-group,
phase 3 study done at 69 study centres in 16 countries across North
America, South America, Europe, and the Asia-Pacific region. Patients
with relapsed or refractory multiple rnyelorna aged at least 18 years
who had received one to three previous lines of therapy and had
measurable serum or urine M-protein were eligible. Patients were
randomly assigned (3:2) to isatuximab plus carfilzomib-dexamethasone
(isatuximab group) or carfilzomib-dexamethasone (control group).
Patients in the isatuximab group received isatuximab 10 mg/kg
intravenously weekly for the first 4 weeks, then every 2 weeks. Both
groups received time approved schedule of intravenous carfilzomib and
oral or intravenous dexamethasone. Treatment continued until progression
or unacceptable toxicity. The primary endpoint was progression-free
survival and was assessed in the intention-to-treat population according
to assigned treatment. Safety was assessed in all patients who received
at least one dose according to treatment received. The study is
registered at ClinicalTrials.gov, NCT03275285.
Findings Between Nov 15,2017, and March 21,2019,302 patients with a
median of two previous lines of therapy were enrolled. 179 were randomly
assigned to the isatuximab group and 123 to the control group. Median
progression-free survival was not reached in the isatuximab group
compared with 19.15 months (95% CI 15.77-not reached) in the control
group, with a hazard ratio of 0.53 (99% CI 0.32-0-89; one-sided
p=0-0007). Treatment-emergent adverse events (TEAEs) of grade 3 or worse
occurred in 136 (77%) of 177 patients in the isatuximab group versus 82
(67%) of 122 in the control group, serious TEAEs occurred in 105 (59%)
versus 70 (57%) patients, and TEA Es led to discontinuation in 15 (8%)
versus 17 (14%) patients. Fatal TEA Es during study treatment occurred
in six (3%) versus four (3%) patients.
Interpretation The addition of isatuximab to carfilzomib-dexamethasone
significantly improves progression-free survival and depth of response
in patients with relapsed multiple myeloma, representing a new standard
of care for this patient population. Copyright (C) 2021 Elsevier Ltd.
All rights reserved.
ER -