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    Singh, Charanpreet; Panakkal, Vandana; Sreedharanunni, Sreejesh; Jandial, Aditya; Jain, Arihant; Lad, Deepesh; Prakash, Gaurav; Khadwal, Alka; Malhotra, Pankaj

    Clinical lymphoma, myeloma and leukemia, 08/2022, Volume: 22, Issue: 8
    Journal Article

    The presence of 2 or more high-risk cytogenetic abnormalities on FISH characterizes patients as Double/Triple Hit Myeloma (DH/THM). This entity has poorer outcomes, though data from the real-world setting is scarce. We retrospectively analyzed all MM patients presenting to our hospital over 3 years to study the clinical characteristics and outcomes with DH/THM. Fifty-five (19.2%) of 285 newly-diagnosed MM patients had DH/THM. The most common cytogenetic abnormality was increased copies of chromosome 1q (53 patients, 96.4%)- 22 patients had 3 copies, and 31 patients had 4 or more copies. The most common cytogenetic combination was IgH-FGFR3 translocation, increasing 1q copy number (28 patients; 50.9%). The disease was characterized by aggressive presentation, with 9 patients (16.4%) dying in the first month after diagnosis, and 7 patients (12.7%) dying in the second month. Only 22 patients (40%) achieved a VGPR or better with therapy. The Median EFS and OS for the cohort were 8 months and thirteen months, respectively. On multi-variate analysis, renal failure and plasma cell leukemia were associated with increased mortality risk, while achievement of VGPR or better was associated with better survival. Our findings suggest that multiple myeloma patients with double/triple hit cytogenetics on FISH have aggressive presentations, high early mortality, and poor outcomes. These patients may benefit from more aggressive regimens and better supportive care. Double-Hit and Triple-Hit cytogenetics in Multiple Myeloma is associated with poor outcomes; however, real-world data is scarce. Our study highlights the aggressive presentation and dismal prognosis of this subgroup of patients in a real-world setting, confirming its “ultra-high-risk” behavior.