P-327: Hyposecretory Progression Pattern Indicates Inferior Survival of Multiple Myeloma

Introduction: Almost all MM patients will eventually progress and relapse either asymptomatically or with end-organ damage. At progression patients always present different features with different levels of M protein and plasma cells in bone marrow (BMPC). Interestingly, some patients who are secretory MM types at diagnosis show higher BMPC percentage but lower M protein when PD. The recognition of this subgroup is still unclear.We evaluated the effect of different progression patterns on the survival according to M protein and BMPC percentage.

Methods: We analyzed baseline and progression features of 211 patients between January 1, 2013 to June 1, 2021 in our hospital. We classify the PD patterns as 3 groups according to the M protein and clonal PCs in bone marrow: a. hyposecretory progression (HypoP) means > 10% increase of the absolute percentage of BMPCs but serum M-protein increase < 5g/L; b. extramedullary progression (EMP) means appearance of a new extramedullary lesion; c. classic progression (ClaP) means any one or more of the other PD criteria according to IMWG criteria. HRCA is defined as the presence of t (4;14), t (14;16) or del (17p) by FISH. Time from the first relapse to death as overall survival after relapse (rel-OS).

Results: We retrospectively analyzed 12 patients (5.7%) and 30 (14.2%) patients who met the new definition of HypoP and EMP, respectively, and 169 (80.1%) patients can be classified as ClaP group. Interestingly, different to other 2 groups, female patients shared more percentage (66.7%) and IgA (50.0%) as well as light chain (41.7%) were the two most common M protein types in HypoP group. As for the clinical features, HypoP patients were more likely to suffer from hypercalcemia, renal dysfunction and lower serum M protein level both at diagnosis and progression. Also, there were more percentage patients in EMP (50.0% and 53.3%) and HypoP (41.7% and 66.7%) presenting HRCA both at diagnosis and progression. The median follow-up is 42.9m (7.8-99.7m). Patients in ClaP and EMP groups experienced similar PFS whereas HypoP patients had significantly shorter median PFS (P=0.001, 20.6m vs. 22.8m vs. 12.9m). We also found that compared to ClaP and EMP groups, patients with HypoP feature had inferior median OS (P < 0.001, 68.4m vs. 47.2m vs. 25.9m) and rel-OS (P < 0.001, 31.2m vs. 16.6m vs. 8.9m). Besides, a Cox-regression multivariate analysis showed ISS-III (HR 0.471, 95% CI 0.312-0.712; P=0.001), higher LDH (HR 0.519, 95% CI 0.310-0.869, P=0.04), EMP (HR 0.547, 95% CI 0.331-0.904. P=0.019) and HypoP (HR 0.241, 95% CI 0.107-0.543. P=0.001) were associated with shorter OS.

Conclusions: In conclusion, our results indicate that the patients at progression presenting increased BMPC but lower M protein are inclined to have aggressive features such as hypercalcemia, renal dysfunction and lower serum M protein level both at diagnosis and progression. Also, the hyposecretory progression pattern is a valuable indicator of inferior survival compared to other progression patterns.