Thornton Macauley^1
1St. Vincent's Hospital Melbourne

Background: In Australia, use of FISH testing for high-risk primary and secondary cytogenetic abnormalities (HRSCA) is well-established in PCM, and Medicare-rebated once per lifetime¹, despite HRSCA also being acquired at relapse. With development of risk-adapted, targeted therapies against these lesions^2,3, benefit may exist in FISH testing at relapse.

Methods: Retrospective cohort study of PCM patients who had FISH testing at a statewide cytogenetics service at diagnosis and at one or more relapses between 01/09/2020-01/09/2023. Testing must have included IGH break-apart and dual-fusion FISH probe testing on a diagnostic bone marrow aspirate specimen, and CDKN2C/CKS1B and TP53/NF1 dual-colour probe testing on both diagnostic and relapse specimen/s. Prevalence and acquisition rates were quantified.

Results: Of 101 eligible patients identified, 12.9% acquired HRSCA at relapse: gain(1q21) 5.9%, del(17p13) 2.0%, del(1p32) 2.0%. 3 patients synchronously acquired multiple HRSCA. 51.5% of patients had one or multiple HRSCA at PCM diagnosis. The primary cytogenetic abnormality of IGH rearrangement was seen in 53.5% of patients. Clone size changes when persisting at relapse were positive, except in del17p cases. 

Conclusion: Acquisition of new HRSCA occurs at PCM relapse. Portending poorer prognosis when detected, this study supports the need for FISH testing at relapse and review of Medicare funding.

 

References:

1. Item 73370 | Medicare Benefits Schedule [Internet]. [cited 2024 Jun 16]. Available from: https://www9.health.gov.au/mbs/fullDisplay.cfm?type=item&q=73370&qt=ItemID

2. Mina R, Musto P, Rota-Scalabrini D, Paris L, Gamberi B, Palmas A, et al. Carfilzomib induction, consolidation, and maintenance with or without autologous stem-cell transplantation in patients with newly diagnosed multiple myeloma: pre-planned cytogenetic subgroup analysis of the randomised, phase 2 FORTE trial. Lancet Oncol. 2023 Jan 1;24(1):64–76.

3. Li J, Stagg NJ, Johnston J, Harris MJ, Menzies SA, DiCara D, et al. Membrane-Proximal Epitope Facilitates Efficient T Cell Synapse Formation by Anti-FcRH5/CD3 and Is a Requirement for Myeloma Cell Killing. Cancer Cell. 2017 Mar 13;31(3):383–95.