Clinical Efficacy and Safety Evaluation of Isazomib Based Combination Regimen for Multiple Myeloma First-Line Therapy
Authors: Bai Yan , Gao Yuhuan , Liu Lihong , Diao Lanping , Wu Xiaolin , Yin Shaoning , Zhang Huilai , Huang Chen 
Published: December 2024

INTRODUCTION
Multiple myeloma (MM) is a hematological malignancy characterized by abnormal clonal proliferation of plasma cells in the bone marrow, resulting in uncontrolled growth and secretion of large amounts of monoclonal immunoglobulin. Currently, Isazomib-based combination regimens are primarily utilized as second and third-line therapies following Bortezomib treatment. Despite demonstrating significant advantages in clinical efficacy and safety, adverse reactions caused by Bortezomib still occur, necessitating further clinical studies.
AIM
The aim of this study was to assess the clinical effectiveness and safety of a combination therapy regimen that includes Isazomib during the first-line chemotherapy in MM patients.
METHOD
We collected clinical data of 38 patients with multiple myeloma who received a combination regimen with an initial dose of 4mg of Isazomib as first-line therapy at the Department of Hematology, the Fourth Hospital of Hebei Medical University from August 2021 to July 2024. Through regular follow-up and International Myeloma Working Group (IMWG) efficacy evaluation criteria, patients' treatment response was evaluated. The patients were evaluated by EQ-5D health score questionnaire. The adverse reactions and drug toxicity of 38 patients during the treatment were collected. Kaplan-Meier method was used to measure the survival curves of 38 patients, univariate analysis was performed, and Cox regression model was used to evaluate multiple prognostic factors.
RESULTS Therapeutic Efficacy: The total response rate (ORR) of 38 MM patients was 78.9% (30/38), including 10 CR, 11 VGPR, and 9 PR. PD rate was 13.2% (5/38), among which 1 progression case was fracture after falling without taking medication for 3 months, 3 cases were due to poor compliance and economic reasons. There were 28 patients (73.6%) adopted one treatment regimen from the beginning to the end of statistics, including 18 patients with IRD regimen, whose ORR rate was 77.8% (14/18), 1 patient with ICAD regimen, whose ORR rate was 100% (1/1), 3 patients with IR regimen, whose ORR rate was 100% (3/3). 3 patients with ICD regimen, whose ORR rate was 100% (3/3) ,1 case of ID scheme (not evaluated), and 1 case of IAD scheme (not evaluated). There were 10 patients who changed the regimen during treatment, including 4 patients with improvement, 2 patients with disease progression,1 patient with transplantation. The 1 -, 2 - and 3-year survival probabilities were 96.3% (95%CI: 89.4%-1), 96.3% (95%CI: 89.4%-1), and the 1 -, 2 - and 3-year progression-free survival probabilities were 90.2% (95%CI: 80.1%-1), 84.2% (95%CI: 70.3%-1), 72.1% (95%CI: 50.7%-1) respectively. Median OS and median PFS were not reached. 37 patients used Isazomib consistently and 1 patient changed to Bortezomib due to increasing creatinine. Eq-5q health score evaluations are as follows: 89.3% of the patients reported no difficulty in moving around, 89.3% reported no difficulty in self-care, 85.7% reported no difficulty in daily activities, 71.4% reported no pain or discomfort, 75.0% reported no anxiety or depression, and the rest of the patients reported mild symptoms.Safety Assessment: 38 patients were generally well tolerated and experienced no major safety concerns after receiving Isazomib combination regimen. Hematological toxicity was observed in 6 cases of leukopenia, 9 cases of thrombocytopenia, and 26 cases of anemia (17 cases were mild). Non-hematological adverse events were mainly comprised of 2 cases of diarrhea, 6 cases of nausea, 2 cases of vomiting, 1 case of fatigue, 1 case of fever, 1 case of dizziness, and 2 cases of rash. One case of grade 1 peripheral neuropathy was reported, with the main symptom being paresthesia in the extremities.Kaplan-Meier and Cox regression models showed that “LDH level” and “sex” were adverse factors affecting OS and PFS in 38 MM patients respectively.
CONCLUSION
This study is a retrospective analysis, and although the number of cases included is limited and there are regional variations as well as significant baseline differences, the overall objective response rate (ORR) is favorable. Additionally, the safety and tolerability profile of the all-oral regimen is satisfactory, with anemia being the main adverse event observed. Therefore, the use of Isazomib in combination with other first-line drugs can enhance treatment adherence and ultimately improve patient survival.