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Outcomes following biochemical or clinical progression in patients with multiple myeloma.

Almost all patients with multiple myeloma (MM) eventually relapse, either asymptomatically or with end-organ damage. However, it remains unclear if initiating therapy at the time of biochemical progression (BP) improves the outcomes, compared with therapy initiation at the clinical progression (CP) stage. Here, we retrospectively assessed 1347 relapsed MM patients. Most progressions were BP (60.4%); 39.6% had CP. The most prevalent symptoms at relapse were: new/evolving bone disease (80.9%), anemia (38.0%) and renal failure (12.7%). Patients with BP had longer median time from 2nd line to next treatment compared to CP (17.0 vs 9.6 months, p<0.001) as well as longer median overall survival from 1st relapse (59.4 vs 26.2 months, p<0.001). Male sex (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.02-2.18; p=0.04), plasma cell labeling index (PCLI) ≥2% (OR 1.58, 95% CI 1.02-2.45, p=0.04) and extramedullary disease at diagnosis (OR 1.84, 95% CI 1.08-3.13. p=0.03) were associated with higher risk of CP, whereas very good partial remission or better had decreased risk of CP (OR 0.62, 95% CI, 0.43-0.91, p=0.02). To conclude, patients with CP have inferior post-progression outcomes compared to patients with BP. Patients with deeper response to first line therapy are less likely to develop CP. The presence of a specific CRAB symptom at diagnosis predicts for the development of similar CRAB symptom at relapse.