How Much Has the Overall Survival of Multiple Myeloma Patients Improved after the Incorporation of New Drugs in the First Line of Treatment in Real-World Experience (RWE)?

Introduction.

The gradual introduction of numerous therapeutic advancements over the last two decades in the treatment of patients with multiple myeloma (MM) has contributed to a significant improvement in overall survival (OS), although it remains an incurable disease. This study aims to analyze the evolution of overall survival in multiple myeloma patients treated at our hospital from 2000 to the present and the impact following the incorporation of various drugs into first line treatment regimens, compared to chemotherapy treatments.

Materials and Methods.

We conducted a single-center retrospective observational study, including all multiple myeloma patients diagnosed between January 1st, 2000, and December 31st, 2022, and treated at the University Hospital of Jerez de la Frontera, which serves as a representative intermediate-level hospital reflecting common clinical practice in our country.

Patients were divided into three calendar periods (2000-2007, 2008-2015, 2016-2022) and two groups (candidates and non-candidates for autologous hematopoietic progenitor transplantation) to analyze the evolution of overall survival (OS). Subsequently, we analyzed the incorporation of proteasome inhibitors (PIs), immunomodulators (IMiDs), and anti-CD38 monoclonal antibodies in the first-line treatment, either as single agents or in combination, compared to the use of chemotherapy treatments. The corresponding approval from the ethics committee has been obtained. For the statistical analysis, the R statistical software (v4.3.3; R Core Team 2021) was used.

Results.

420 myeloma patients were included in the study, with a median age of 64 years. Median survival steadily improved from 50.72 months (33.88 - 73.22; 95% CI) in 2000-2007 to 72.46 months (57.5 - 98.2; 95% CI) in 2008-2015, and has not yet been reached in the 2016-2022 cohort (p= 0.008). OS improved in all age groups, even in older patients. The improve in the OS was more dramatic in the trasplant elegibily patients. The group of patients who underwent autologous transplantation had a median overall survival of 132.66 months (113.32 - 150.98; 95% CI) compared to 38.81 months (31.57 - 51.61; 95% CI) in the non-transplanted patients.

Regarding the incorporation of new therapies in induction treatment, all drug classes showed a significant increase in survival compared to chemotherapy. The median OS increased from 56.7 months in the chemotherapy group to 78.8 months in the proteasome inhibitor (PI) group (p=0.03), 99.4 months in the immunomodulator (IMiD) group (p=0.00002), and the median survival was not reached in the anti-CD38 group (p=0.002). It is noteworthy that only 50.8% of patients used PIs in the first line in combination with other new drugs, while this percentage increase to 86% in the case of IMIDs and to 100% in the case of anti-CD38. This is likely the reason why, in separate analyses of patient groups undergoing and not undergoing autologous transplantation, only IMiDs and anti-CD38 agents achieved statistical significance, underscoring the important role of drug combinations.

Conclusions.

In our patient cohort, an increase in overall survival is observed in each time period and in both groups of patients (transplanted and non-transplanted), although the differences are more pronounced in the group of patients undergoing transplantation. The incorporation of proteasome inhibitors, immunomodulators and anti-CD38 showed significant differences in terms of overall survival, particularly when used in combination. The main limitation of our study is that we did not analyze the incorporation of different drug classes in subsequent lines of treatment. However, it is an established axiom in the field of multiple myeloma to use the best drugs in the earliest phases.

No relevant conflicts of interest to declare.