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Updated: Jan 30, 2026
An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
Published on: July 15, 2015
Progression with clinical features is associated with worse subsequent survival in multiple myeloma
Rajshekhar Chakraborty1, Hien D Liu2, Lisa Rybicki1
1Taussig Cancer Center, Department of Hematology and Medical Oncology, Cleveland Clinic, Cleveland, OH.
Abstract:
Response rate and survival in multiple myeloma (MM) has improved in the era of proteasome inhibitors and immunomodulatory drugs. However, most patients eventually relapse with biochemical progression (BP) alone or with clinical features of end-organ damage (CP: clinical progression), without or without extramedullary (EM) disease. We conducted a retrospective cohort study of 252 patients with MM experiencing first relapse (time, T0 ) to evaluate survival following CP with and without EM as a function of BP. Patients were divided into three groups: BP (n = 134; 53%), CP/EM- (n = 87; 35%) and CP/EM+ (n = 31; 12%). The median time from diagnosis to T0 was significantly shorter in CP/EM+ compared to CP/EM- and BP groups (13 vs 25 vs 25 months; P < 0.001). The incidence of abnormal metaphase cytogenetics at diagnosis was significantly higher in CP/EM+ compared to CP/EM- and BP groups (46% vs 18% vs 11% respectively; P < 0.001). At a median follow-up of 26 months from T0 , median overall survival was 50, 19 and 10 months for BP, CP/EM- and CP/EM+ groups, respectively (P < 0.001). On multivariable analysis, pattern of progression was a significant prognostic factor for OS (HR for CP/EM- vs BP: 3.6; CP/EM+ vs BP: 8.7 and CP/EM+ vs CP/EM-: 2.42; P < 0.001 for all comparisons), along with age at T0 . In conclusion, progression pattern is an important prognostic factor in the current era, with subsequent survival being dismal in patients with end-organ damage or EM disease at relapse. Clinical trials in relapsed MM should consider reporting patterns of progression at baseline to ensure balance between study arms.
Insights
In relapsed multiple myeloma (MM), the pattern of disease progression significantly impacts survival. Patients with clinical progression and extramedullary disease (EM) face dismal outcomes, highlighting the need for tailored clinical trial designs.
Area of Science:
- Hematology
- Oncology
- Clinical Research
Background:
- Multiple myeloma (MM) treatment has advanced with proteasome inhibitors and immunomodulatory drugs, improving response rates and survival.
- Despite advances, most MM patients eventually experience relapse, characterized by biochemical progression (BP) or clinical progression (CP) with or without extramedullary (EM) disease.
Purpose of the Study:
- To evaluate survival outcomes in patients with relapsed multiple myeloma based on the pattern of disease progression.
- To identify prognostic factors associated with different relapse patterns in MM.
Main Methods:
- Retrospective cohort study of 252 patients with MM at first relapse (T0).
- Patients categorized into three groups: biochemical progression (BP), clinical progression without EM disease (CP/EM-), and clinical progression with EM disease (CP/EM+).
- Analysis of time to relapse, cytogenetics, and overall survival (OS) from T0.
Main Results:
- The CP/EM+ group had a shorter median time from diagnosis to relapse (13 months) compared to CP/EM- and BP groups (25 months).
- Abnormal metaphase cytogenetics were more frequent in the CP/EM+ group (46%) than in CP/EM- (18%) and BP (11%) groups.
- Median OS from T0 was 50 months for BP, 19 months for CP/EM-, and 10 months for CP/EM+.
- Progression pattern, along with age at T0, was a significant prognostic factor for OS on multivariable analysis.
Conclusions:
- The pattern of disease progression is a critical prognostic factor in relapsed multiple myeloma.
- Patients with clinical progression and extramedullary disease at relapse have significantly poorer survival outcomes.
- Future clinical trials in relapsed MM should stratify patients by progression patterns to ensure balanced study arms and accurate outcome assessment.
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