Association of Morbid Progression With Overall Survival Among Patients With Multiple Myeloma: Validation of the Progression-free Survival Endpoint

• Published in: Clinical lymphoma, myeloma and leukemia Vol. 21; no. 5; pp. 345 - 354.e4
• Main Authors: Rosenberg, Aaron S., Facon, Thierry, Parikh, Kejal, Chung, Weiyuan, Srinivasan, Shankar, Kotey, Stanley, Tuscano, Joseph
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2021
• Subjects: Aged; Aged, 80 and over; Anemia; Female; Humans; Hypercalcemia; Hypercalcemia - etiology; Male; Middle Aged; Multiple Myeloma; Multiple Myeloma - mortality; Multiple Myeloma - physiopathology; Progression; Progression-Free Survival; Renal insufficiency; Hypercalcemia; Progression; Renal insufficiency; Anemia; Multiple Myeloma
• ISSN: 2152-2650; 2152-2669
• DOI: 10.1016/j.clml.2020.12.021

Multiple myeloma (MM) is an incurable malignancy, marked by end-organ damage that is frequently irreversible. Progressive disease (PD) can be defined as morbid PD, associated with new-onset hypercalcemia, renal insufficiency, anemia, or lytic bone lesions (CRAB symptoms), or as asymptomatic biochemical progression. The frequency of morbid versus asymptomatic PD and its effect on survival is unknown. Our aim was to determine the incidence of morbid PD, and to evaluate if this influences survival. Data from 2 phase III trials of transplant-ineligible patients with newly diagnosed MM were included in a post hoc analysis. Of 2082 patients enrolled, 1243 (59.7%) experienced PD. At first progression, 543 (43.7%) patients had morbid PD; 12 (2.2%) had hypercalcemia, 271 (49.9%) had renal insufficiency, 370 (68.1%) developed anemia, and 79 (14.5%) developed new or enlarged bone lesions. A total of 700 (56.3%) patients had asymptomatic PD. Patients with morbid PD had worse second progression-free survival (PFS) versus patients with asymptomatic biochemical PD (median second PFS, 11.5 months vs. 20.0 months; hazard ratio, 1.63; 95% confidence interval, 1.43-1.85; P < .0001) and worse overall survival (OS) (median OS, 23.2 months vs 39.3 months; hazard ratio, 1.51; 95% confidence interval, 1.30, 1.74; P < .0001). Morbid PD occurs frequently and is associated with inferior second PFS and OS. As CRAB symptoms may not reverse with therapy, morbid PD is a meaningful event, and its association with a shortened PFS adds validity to PFS as a relevant endpoint in patients with MM. •Morbid PD in MM can cause end-organ damage.•Morbid PD in MM is associated with poor PFS and OS.•Patients with MM require routine monitoring to identify signs of end-organ damage. The effect of morbid versus asymptomatic progressive disease (PD) on survival in multiple myeloma is unknown. A post hoc analysis of 2 phase III trials (N = 2082) showed that 43.7% and 56.3% of patients had morbid or asymptomatic PD, respectively. Morbid PD was associated with inferior progression-free survival and overall survival, and is a clinically meaningful event in multiple myeloma.