Phase 2 trial of ixazomib in patients with relapsed multiple myeloma not refractory to bortezomib.
This phase 2 trial was designed to evaluate ixazomib, an orally bioavailable proteasome inhibitor, in patients with myeloma who have limited prior exposure to bortezomib. Thirty-three patients with relapsed multiple myeloma were enrolled. Ixazomib was given at 5.5 mg weekly for 3 of 4 weeks. Dexamethasone was added for lack of a minor response (MR) by end of cycle 2 or lack of a partial response (PR) by end of cycle 4 or for disease progression at any time. Median age was 69 years; patients had a median of two prior therapies (range 1-7). A grade 3 or 4 adverse event considered at least possibly related to drug was seen in 19 (59%) and 6 (19%) patients, respectively. The most common adverse events were thrombocytopenia, fatigue, nausea and diarrhea. Dexamethasone was initiated in 22 (67%) patients, 17 for not reaching the desired response and 5 for progression. Response (⩾PR) to single agent was seen in five patients within four cycles of therapy including three patients with PR, one patient with complete response (CR) and one patient with stringent CR. Six additional patients with either an MR (2) or SD (4) achieved a PR after addition of dexamethasone, translating to an overall response rate of 34%.
Division of Hematology, Mayo Clinic, Rochester, MN, USA.
S K
SK
Kumar
Department of Biostatistics, Mayo Clinic, Rochester, MN, USA.
B
B
LaPlant
Division of Hematology and Oncology, Mayo Clinic, Jacksonville, FL, USA.
V
V
Roy
Division of Hematology and Oncology, Mayo Clinic, Scottsdale, AZ, USA.
C B
CB
Reeder
Division of Hematology, Mayo Clinic, Rochester, MN, USA.
M Q
MQ
Lacy
Division of Hematology, Mayo Clinic, Rochester, MN, USA.
M A
MA
Gertz
Department of Biostatistics, Mayo Clinic, Rochester, MN, USA.
K
K
Laumann
Division of Hematology, Mayo Clinic, Rochester, MN, USA.
M A
MA
Thompson
Division of Hematology, Mayo Clinic, Rochester, MN, USA.
T E
TE
Witzig
Division of Hematology, Mayo Clinic, Rochester, MN, USA.
F K
FK
Buadi
Division of Hematology and Oncology, Mayo Clinic, Jacksonville, FL, USA.
C E
CE
Rivera
Division of Hematology and Oncology, Mayo Clinic, Scottsdale, AZ, USA.
J R
JR
Mikhael
Division of Hematology and Oncology, Mayo Clinic, Scottsdale, AZ, USA.
P L
PL
Bergsagel
Division of Hematology, Mayo Clinic, Rochester, MN, USA.
P
P
Kapoor
Division of Hematology, Mayo Clinic, Rochester, MN, USA.
L
L
Hwa
Division of Hematology and Oncology, Mayo Clinic, Scottsdale, AZ, USA.
R
R
Fonseca
Division of Hematology and Oncology, Mayo Clinic, Scottsdale, AZ, USA.
A K
AK
Stewart
Division of Hematology and Oncology, Mayo Clinic, Jacksonville, FL, USA.
A
A
Chanan-Khan
Division of Hematology, Mayo Clinic, Rochester, MN, USA.
S V
SV
Rajkumar
Division of Hematology, Mayo Clinic, Rochester, MN, USA.
A
A
Dispenzieri
D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001896:Boron Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D005998:Glycine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality; D012008:Recurrence; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001896:Boron Compounds; C548400:ixazomib; D003907:Dexamethasone; D005998:Glycine