Clinical Features and Outcomes of Patients with Double-Hit/Triple-Hit Multiple Myeloma Detected at Relapse.

Introduction: mSMART classifies high-risk Multiple Myeloma patients into Double Hit and Triple Hit Myeloma (DH/THM) on the basis of the number of high-risk cytogenetic abnormalities detected. We aimed to study the clinical profile and outcomes of patients with DH/THM detected at relapse in a real-world setting. Methods: The case records of all relapsed multiple myeloma patients with DH/THM diagnosed between January 2018 and December 2020 were identified and information regarding baseline characteristics, therapy and outcomes was noted. Results: Seventeen patients were diagnosed with DH/THM at relapse during the study period. Twelve patients (70.6%) were in first relapse, while 3 patients were diagnosed at second relapse and 1 patient each at 3rd and 5th relapse respectively. The most common cytogenetic combination was IgH-FGFR3 translocation with gain of 1q (seen in 10 patients; 58.8%). Ten patients (58.8%) died within the first 2 months of diagnosis and 16 patients (94.1%) died during follow up (range 0-16 months). The most common cause of death was progressive/active disease (9 patients, 56.3%). Discussion: The outcome of DH/THM at relapse is associated with an aggressive presentation and poor outcomes in the real-world setting. These patients are candidates for early aggressive or novel therapy or clinical trials.

Presentation and Impact of Double and Triple hit Cytogenetics in Patients With Multiple Myeloma in the Real World.

INTRODUCTION: 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. PATIENTS AND METHODS: We retrospectively analyzed all MM patients presenting to our hospital over 3 years to study the clinical characteristics and outcomes with DH/THM. RESULTS: 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. CONCLUSION: 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.

The success rate of interphase fluorescence in situ hybridization in plasma cell disorders can be improved using unconventional sources of plasma cells.

BACKGROUND: Immunomagnetic cell sorting (IMCS) is a preferred technique for the enrichment of plasma cells (PC) before fluorescence in situ hybridization (FISH). Here, we share our real-world experience regarding the success rate of IMCS, its limitations, and the utility of alternate sources to obtain a successful FISH in various PC disorders. MATERIALS AND METHODS: A retrospective analysis was performed in patients with a PC neoplasm, who underwent bone marrow (BM) examination, and FISH testing over 30 months. In all cases with an unsuccessful IMCS, an attempt was made to identify the cause of failure. RESULTS: Immunomagnetic cell sorting of PCs was successful in 395/450 cases (87.8%; 77/98 cases (78.6%) with <10% PCs and 318/352 (90.3%) with ≥10% PCs in BM aspirate; P = .003). Among cases with unsuccessful IMCS (<10% PCs; n = 21 and ≥10% PCs; n = 34), an alternate source could be used successfully in 34 (62%) patients and includes air-dried trephine biopsy imprint smears (n = 28) with aggregates or sheets of PCs, fine-needle aspiration smears/biopsy from plasmacytoma (n = 5), and ascitic fluid (n = 1). 284/395 (71.9%) patients with successful IMCS and all 34 cases with an alternate source of PCs showed at least one cytogenetic abnormality on four-probe FISH. CONCLUSION: Variations in the sample quality together with significant variation in the number of PCs between BM aspirate and the trephine biopsy imprint smears/biopsy reduce the success rate of IMCS in a real-world scenario and necessitate utilization of patient-specific alternate sources of PCs like a trephine biopsy imprint or cytology smears from extramedullary sources for successful FISH testing in PC neoplasms.