Abstract Aims Studies have shown that bortezomib retreatment is effective in relapsed/refractory multiple myeloma (MM). The observational, prospective electronic VELCADE ® OBservational Study (eVOBS) study assessed bortezomib‐based therapies for patients with MM in everyday practice. Here, we report on those patients receiving retreatment with bortezomib. Methods Consenting adults scheduled to receive bortezomib for MM were enrolled at 162 sites across Europe, Canada, Brazil, Russia, and Turkey between 2006 and 2010. Retrospective data on prior therapies and prospective observational data after bortezomib initiation were captured electronically at baseline, after every bortezomib cycle, and every 12 weeks after discontinuation or progression. Investigator‐assessed responses and adverse events (AEs) were evaluated. Results Ninety‐six of 873 patients enrolled to eVOBS received bortezomib as first retreatment for progressive disease during the prospective observation period. Median age was 62 years, 53% were male, and median number of prior therapies at retreatment was 4. Overall, 41% of patients initiated bortezomib retreatment in combination with dexamethasone, 16% in combination with lenalidomide, and 21% received monotherapy. Rate of partial response or better (≥PR) was 75% at initial bortezomib therapy, including 44% complete response (CR)/near CR (nCR); at retreatment, ≥PR rate was 46%, including 15% CR/nCR. Median progression‐free survival was 11.4 months (95% confidence interval [CI]: 9.1‐12.7) from start of initial bortezomib treatment and 6.4 months (95% CI: 4.4‐7.2) from start of retreatment. Median overall survival from start of retreatment was 17.6 months (95% CI: 14.4‐23.5). Of the 96 patients retreated with bortezomib, 77% reported an AE. Peripheral neuropathy during bortezomib retreatment occurred in 49% of patients, including 10% grade 3/4. Conclusion These data suggest that retreatment with bortezomib is a feasible option for patients with relapsed/refractory MM.
Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: The treatment of Multiple Myeloma (MM) has changed dramatically over the past two decades with the introduction of new drugs, including immunomodulators (thalidomide, lenalidomide, pomalidomide), proteasome inhibitors (bortezomib, carfilzomib, ixazomib) and anti-CD38 monoclonal antibodies (daratumumab). Aims: This study aimed to estimate the survival of patients with a first diagnosis of MM. Methods: This retrospective observational cohort study was carried out in the general population using data from 2 hematological malignancies registers (Gironde, Côte-d’Or) and included all new adult patients diagnosed with MM between 2008 and 2015. Patients were followed from diagnosis until death/end of study in December 2020, allowing a follow-up period of at least 5 years for each patient included. Time to next treatment (TTNT), progression-free survival (PFS), and overall survival (OS) were estimated using the Kaplan-Meier method. Net survival defined as the observed survival if cancer was the only possible cause of death, was also estimated. Results: The analysis was carried out on 1166 patients included. The median age was 74 years (Q1-Q3; 63-82 years) with a slightly unfavorable M/F gender ratio of 1.1. In this cohort, 923 patients (79%) had initiated treatment. Bortezomib, thalidomide and/or lenalidomide were used in first line of therapy in most cases (n=825/923, 89% of patients in 2015 vs 80% in 2008). Overall, the median follow-up time was 4.9 years, 52% of patients had died, and 1% (n=11) was lost in follow-up. Median OS for treated patients was 4.9 years (95% confidence interval [CI]:4.6, 5.3). Median OS was worse in the subgroup of patients who didn’t have a stem cell transplantation (SCT) versus those who did (3.6 vs 9.8 years), and in elderly patients (≥80 years) compared with patients <65 (2.1 vs 9.8 years). The estimated 5-year net survival was 55% for the entire cohort of treated patients and was higher among patients treated more recently (58% in 2015 vs 45% in 2008). Median PFS was 2.3 years (95% CI: 2.1, 2.4) for the entire cohort of treated patients. Median TTNT from first line to second line of therapy was 1.9 years (95% CI; 1.7, 2.1) and decreased in older patients: it was 2.6 years (95% CI: 2.3, 2.9) in patients <65 years, 2.1 years (95% CI; 1.7, 2.3) in those aged between 65 and 79, and 1.1 years (95% CI: 0.9, 1.3) in patients aged ≥80. Summary/Conclusion: These results provide important information on the efficacy of MM treatments available in France during the study period. Consistent with the 2021 published INCa data showing the 5-year net survival improved between 1995 and 2015, particularly in the youngest patients, and is expected to continue to improve in the coming years. Keywords: Treatment, Multiple myeloma, Real world data
The wide heterogeneity in multiple myeloma (MM) outcome is driven mainly by cytogenetic abnormalities. The current definition of high-risk profile is restrictive and oversimplified. To adapt MM treatment to risk, we need to better define a cytogenetic risk classification. To address this issue, we simultaneously examined the prognostic impact of del(17p); t(4;14); del(1p32); 1q21 gain; and trisomies 3, 5, and 21 in a cohort of newly diagnosed patients with MM.Data were obtained from 1,635 patients enrolled in four trials implemented by the Intergroupe Francophone du Myélome. The oldest collection of data were used for model development and internal validation. For external validation, one of the two independent data sets was used to assess the performance of the model in patients treated with more current regimens. Six cytogenetic abnormalities were identified as clinically relevant, and a prognostic index (PI) that was based on the parameter estimates of the multivariable Cox model was computed for all patients.In all data sets, a higher PI was consistently associated with a poor survival outcome. Dependent on the validation cohorts used, hazard ratios for patients in the high-risk category for death were between six and 15 times higher than those of patients in the low-risk category. Among patients with t(4;14) or del(17p), we observed a worse survival in those classified in the high-risk category than in those in the intermediate-risk category. The PI showed good performance for discriminating between patients who died and those who survived (Harrell's concordance index greater than 70%).The cytogenetic PI improves the classification of newly diagnosed patients with MM in the high-risk group compared with current classifications. These findings may facilitate the development of risk-adapted treatment strategies.
