Abstract
Background：
During the past decade, bortezomib, lenalidomide and dexamethasone (VRd) followed by lenalidomide maintenance has become one of the most effective first-line regimens in multiple myeloma (MM) and been recommended by many guidelines. However, when disease relapses after VRd induction and lenalidomide maintenance, further generation of proteasome inhibitors or immunomodulator drugs, or agents with different mechanism should be considered. Pomalidomide, a new-generation oral immunomodulator drug, can overcome lenalidomide resistance and has better efficacy and safety in MM patients. Pomalidomide has a synergistic effect with proteasome inhibitor and dexamethasone, which has been proved more effective than pomalidomide and dexamethasone dual-drug regimen in relapsed or refractory MM (RRMM) patients (Richardson, et al. Lancet Oncol 2019). The overall response rate (ORR) of lenalidomide retreatment is only 54% (Sumit, et al. Blood 2011). A convenient and safe pan-oral regimen, ixazomib, pomalidomide and dexamethasone (IxaPd) is expected to improve the efficacy and survival in RRMM patients. The purpose of this study is to evaluate the efficacy and safety of IxaPd regimen in RRMM patients who have received lenalidomide in China.
Study Design and Methods:
This multi-center open-label, single-arm study (NCT04989140) will enroll patients with measurable M protein who have received 1 to 3 prior lines of therapy (including lenalidomide) with documented disease progression during or after their most recent treatment. Patients aged ≥18 years with Eastern Cooperative Oncology Group Performance Status 0-2, expected overall survival (OS) ≥3 months, and who provide informed consent will be eligible. Patients with prior exposure to pomalidomide, ixazomib and those intolerant/refractory to bortezomib will be excluded.
Eligible 60 patients will be enrolled in this IxaPD regimen. Clinical and laboratory parameters will be recorded at baseline. Cytogenetic abnormalities are tested via fluorescence in situ hybridization (FISH) in CD138 sorted myeloma cells. Ixazomib 4 mg on days 1, 8 and 15 every 28 days, pomalidomide 4mg qd day 1-21 every 28-day, dexamethasone 40 mg (20 mg for patients >75 years of age) every week will be administrated. Treatment will continue until disease progression or unacceptable toxicity. Drug doses will be adjusted or withdrawn according to the degree of toxicities. The primary endpoint is progression free survival (PFS), the secondary endpoints include OS, time to next treatment (TTNT), ORR, safety. Patients are stratified into subpopulation on the basis of cytogenetic abnormalities, prior treatment lines and exposure drugs, ect. PFS, OS and TTNT were analyzed by Kaplan-Meier survival plot. Response will be evaluated according to International Myeloma Working Group (IMWG) 2016 criteria, and done at baseline and each cycle from 1-5, then every other cycle till cycle 13, and every three cycles till cycle 28 if the subjects do not relapse. Patients who reach complete response (CR) need to perform a minimal residual disease (MRD) test via next‐generation flow (NGF) .
Conclusion:
This is the first prospective clinical study to examine the efficacy and safety of pan-oral IxaPd regimen for RRMM in Chinese patients.
Disclosures
Research sponsor: CHIATAI TIANQING PHARMACEUTICAL GROUP.
No relevant conflicts of interest to declare.
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