The Prognostic Significance of Acquired 1q22 Gain in Multiple Myeloma

• Published in: Blood 2020-11, Vol.136 (Supplement 1), p.9-10
• Main Authors: Audil, Hadiyah Y., Cook, Joselle, Greipp, Patricia, Kapoor, Prashant, Baughn, Linda B, Dispenzieri, Angela, Gertz, Morie A, Buadi, Francis K., Lacy, Martha Q., Dingli, David, Fonder, Amie, Hayman, Suzanne R., Hobbs, Miriam A., Muchtar, Eli, Siddiqui, Mustaqeem A., Gonsalves, Wilson I, Hwa, Yi L., Leung, Nelson, Go, Ronald S., Lin, Yi, Kourelis, Taxiarchis, Warsame, Rahma M, Lust, John A., Kyle, Robert A., Ketterling, Rhett P., Rajkumar, S. Vincent, Kumar, Shaji K.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2020-139093

Background: Within the heterogeneous genomic landscape of multiple myeloma (MM), clonal evolution including the acquisition of risk-defining mutations and chromosomal abnormalities is a recurrent event and can be detected by fluorescence in situ hybridization (FISH). The effects of acquired abnormalities on clinical outcomes have not been well defined. We previously reported that patients who acquired 17p deletion [del(17p)] during the course of their disease had a significantly reduced overall survival (OS) by 38 months compared to patients who did not acquire del17p (Lakshman et al 2019). Similarly, while de novo gain of the long arm of chromosome 1 (1q22 gain) is a known high-risk aberration associated with significantly shorter OS and progression-free survival (PFS) in MM, the prognostic significance of acquired 1q22 gain has not been described. The primary objective of this study was to analyze factors predictive for acquired 1q22 gain and determine its impact on survival. Methods: We identified MM patients from the Mayo Clinic Dysproteinemia Database who had at least one follow up FISH performed ≥6 months from diagnosis. The clinical characteristics, concomitant cytogenetic abnormalities, first line treatments administered, and OS were compared between patients with acquired 1q22 gain and patients who did not acquire this abnormality. The Mayo Clinic IRB approved this study. Results: A total of 1041 MM patients met the inclusion criteria. Of these, 63 patients (6.1%) had acquired 1q22 gain, defined as being negative for 1q22 gain on initial FISH at diagnosis and having this abnormality detected on subsequent FISH. Median age at diagnosis was 59 years and 56% were male. Median time to acquisition of 1q22 gain was 60 months (range 8-140 months). We identified one control patient for each case who was diagnosed within one year of the case and had a subsequent FISH performed at a similar duration from diagnosis. Patients with acquired 1q22 gain had similar baseline characteristics except for a higher proportion of high-risk (HR) FISH at diagnosis [t(4;14), t(14;16), t(14;20), and del(17p13)] when compared to controls (27% HR FISH versus 6% HR FISH; P