Overall and complete response rates as potential surrogates for overall survival in relapsed/refractory multiple myeloma

• Published in: Future oncology (London, England) Vol. 19; no. 6; pp. 463 - 471
• Main Authors: Daniele, Patrick, Mamolo, Carla, Cappelleri, Joseph C, Bell, Timothy, Neuhof, Alexander, Tremblay, Gabriel, Musat, Mihaela, Forsythe, Anna
• Format: Journal Article
• Language: English
• Published: England Future Medicine Ltd 01.02.2023
• Subjects: Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Dexamethasone - therapeutic use; Humans; multiple myeloma; Multiple Myeloma - drug therapy; overall response rate; overall survival; relapsed refractory; Remission Induction; response; surrogate endpoint; multiple myeloma; relapsed refractory; OS; response; surrogate end point; overall survival; overall response rate
• ISSN: 1479-6694; 1744-8301; 1744-8301
• DOI: 10.2217/fon-2022-0932

The correlation between response and survival has not been well-studied in relapsed or refractory multiple myeloma (RRMM). A systematic literature review of Medline, Embase and Cochrane databases (2010–06/2020) and relevant congresses (2018–2020) was performed to identify randomized clinical trials in RRMM reporting median overall survival (mOS), progression-free survival and response endpoints. The relationship between mOS and response endpoints was analyzed using Pearson’s product-moment correlation. A total of 81 records for 65 original studies, representing 12,827 patients were included. The correlation was moderate for mOS with overall response rate (Pearson r = 0.79), very good partial response (r = 0.73) and duration of response (r = 0.78); all were statistically significant. In linear regression models, estimated mOS gain was 0.48, 0.47 and 1.94 months per percentage point of overall response rate, very good partial response and complete response, respectively (all p < 0.001). Significance was maintained after adjustment for age, relapsed versus refractory multiple myeloma and study year. The analysis was limited by small sample sizes and inconsistent reporting of study-level covariates. These findings support short-term response-based endpoints as surrogates to survival in RRMM. Treatments for multiple myeloma may not work for every patient and the cancer may come back. In clinical trials, it is difficult to find out how well new treatments work in allowing patients to live longer. This is especially true when patients have advanced disease that has returned or has not responded to treatment. How well a patient responds to treatment (i.e., has a decreased extent of disease) could indicate whether the drug will help the patient live longer, but the relationship between response to treatment and survival is not fully understood. We conducted a systematic review and meta-analysis to better understand how response rates and survival are related. A systematic review collects all the published research on a specific subject, and a meta-analysis is a statistical method that creates a single finding from several separate studies. This study found a moderate relationship between how long patients live after receiving treatment for multiple myeloma and their response to treatment. This would allow response-to-treatment data from clinical trials to be used to predict better survival and show the drug can help patients. Potential surrogate? Overall response rate, very good partial response and duration of response were all shown to have a significant, moderate correlation with overall survival among relapsed or refractory multiple myeloma patients.