P-161: Ultra-high-risk prognostic significance of double and triple hit myeloma

Abstract

<h3>Background</h3> Association of any of 2 or ≥3 specific high-risk chromosomal abnormalities (HR-CA: t(4;14), t(14;16), t(14;20) and +1q21) in multiple myeloma (MM) characterizes double or triple hit MM. <h3>Aims</h3> The aim of study was to evaluate prognostic significance of iFISH findings of double and triple hit MM on the course of disease. <h3>Methods</h3> The study analysed iFISH findings, clinical and laboratory characteristics of 502 newly diagnosed, transplant ineligible patients (pts, 259 male; 243 female, mean age 62yrs, range 35-85yrs) during period 2009-2021. According to the MM type, IgG MM was found in 297pts (60.4%), IgA in 100 (20.3%), BJ in 88 (17.9%), IgD in 5pts (1.0%) and IgM and non-secretory disease was found at 1pts each (0.2%). The clinical stage (CS, Durie-Salmon) III was confirmed in 397pts (79.6%); II 73pts (14.6%); and I with symptomatic disease 29pts (5.8%). The ISS score 1 had 135pts (28.7%), ISS2 112pts (23.8%), and 224pts (47.6%) had ISS3. Revised ISS score 1 (R-ISS1) was found in 100pts (21.8 %); R-ISS2 in 254pts (55.5%), and R-ISS3 in 104pts (22.7%). Renal impairment had 160pts (32%). Treatment with thalidomide (Thal) based chemotherapy (HT) was applied in 254pts (50.7%); bortezomib (Bz) based HT in 186pts (37.1%), while 56pts (11.2%) were treated with conventional HT. <h3>Results</h3> Finding of double and triple hit MM was identified in 21pts (6.8%): 17pts with double; 4pts with triple hit MM (12 male, 9 female, mean age 65yrs, range 44-81yrs). The IgG MM was present in 11pts, IgA in 5pts, and BJ in 5pt. Majority, 17pts were in III CS, and 4pts in II CS. The ISS3 score had 14pts, ISS2 5pts, ISS1 2pts, while R-ISS3 was found in 12pts, and R-ISS2 in 9pts. The overall treatment response (ORR, ≥PR) was significantly lower in pts with double and triple hit MM in comparison to the other MM patients (61.9% vs. 78.2%, p=0.018). The average PFS of patients with double and triple hit MM was significantly shorter in comparison to other MM patients, (17.0m vs. 48.0m; Log Rank=12.471, p<0.01); as well as the average OS of patients with double and triple hit MM (18.0m vs. 64.0m; Log Rank=10.593, p<0.01). Univariate Cox regression analysis pointed out the age (p<0.01), elevated LDH (p<0.01), R-ISS score (p<0.01) and presence of double and triple hit MM (p<0.01), as the major prognostic factors with impact on the OS of myeloma patients. Furthermore, the multivariate analysis confirmed major prognostic significance of age (p=0.02) and double and triple hit myeloma (p<0.01) for the OS. <h3>Conclusion</h3> Presence of double and triple hit myeloma indicates ultra high-risk course of disease, consequently indicating necessity of intensive treatment approach with new treatment modalities.