A Prospective, Multinational Study of Clinical and Biological Factors Associated with Short Overall Survival in Multiple Myeloma

Introduction: Multiple myeloma (MM) is an incurable cancer, but a subset of patients can achieve long-term remission and overall survival (OS). We aimed to study the clinical and biological factors associated with short OS defined as less than 3 years.

Methods: A prospective, observational, multinational study was conducted by Australian and New Zealand (ANZ) and Asia-Pacific (APAC) Myeloma and Related Disease Registry (MRDR) from January 2013 to January 2023, across 5 countries (Australia, New Zealand, Korea, Singapore, Malaysia). Eligible patients were ≥18 years old, diagnosed with MM per International Myeloma Working Group (IMWG) criteria, received a bortezomib-containing triplet, and had at least 3 years of follow-up or had deceased within 3 years. Descriptive analysis was completed using chi-squared test for categorical variables and Wilcoxon rank-sum test for continuous variables. The Kaplan-Meier method was used for analysing OS and follow-up data. The ‘stepwise’ function in Stata was used for the forward stepwise logistic regression, with the p-value set to 0.1. All analyses were completed using Stata 16.

Results: Of the 1539 patients enrolled, majority were from ANZ (1071 and 359, respectively), with male preponderance (61.0%). Half were above 65 years old. High risk cytogenetic abnormalities, a criterion of the Revised International Staging System (R-ISS), was unknown for half of the patients (49.4%). 45.3% patients presented as ISS stage 1, 21.9% stage II, and 32.8% stage III, respectively at study entry. The most frequent front-line agent used in combination with bortezomib-based triplet was cyclophosphamide [VCd, 1380 (89.7%)], followed by thalidomide [VTd, 92(6.0%)], lenalidomide [VRd, 63 (4.1%)] and daratumumab [DVd, 4 (0.3%)]. The median follow-up was 29.9 months (95%CI: 28.3-31.8) and the median OS was 87.7 months (95%CI: 80.9-93.2). Thirty percent patients had OS<3 years. Clinical and biological factors associated with long OS (≥3 years) were compared with those <3 years (Table 1). Baseline factors associated with higher odds of short OS included age≥65, Eastern Cooperative Oncology Group performance status (ECOG PS)≥2, ISS III, lower creatinine clearance and platelet count, high LDH and poor cytogenetic abnormalities (Table 1). In a multivariate analysis, age≥65 (OR:2.50; p<0.001), ECOG≥2 (OR:2.08; p<0.001), ISS III (OR:2.48; p<0.001), t(4;14)[OR:2.04; p=0.004], t(14;16)[OR:6.33; p=0.004] and 17p deletion (OR:2.77; p=0.001) were associated with a significantly shorter OS.

Conclusion: From clinician perspective, identifying patients with an increased likelihood of shorter OS through the determination of patient- and disease-specific risk factors might be clinically relevant to facilitate better treatment decisions.