Clinical Characteristics and Outcomes in Patients with Multiple Myeloma and CKS1B Gene Gain/Amplification after Autologous Stem Cell Transplantation

Background: The gain/amplification of the CKS1B gene that is located on chromosome 1q21 is a predictor of poor outcome in multiple myeloma (MM). However, there are little data in the literature on the characteristics and outcomes of patients with this cytogenomic marker. Historically, median PFS after auto-HCT for all patients with multiple myeloma is 24-30 months in patients transplanted in 1^st remission and 12-16 months in patients transplanted for relapsed disease. We wanted to compare the outcomes of patients with CKS1B amplification with the historical data.

Methods: This is a single-center retrospective analysis of patients with MM, who received high-dose chemotherapy and autologous hematopoietic stem cell transplantation (auto-HCT) at our institution between 2011 and 2014. We identified 64 patients, 8.2% of 777 auto-HCT performed during this period, who had CKS1B gain/amplification on FISH studies, or chromosome 1q21 gain on conventional cytogenetics. The primary objective was to describe the clinical characteristics and outcome of these patients, including progression-free (PFS) and overall survival (OS).

Results: Median age at auto-HCT was 60.4 years (range 34-79). Median interval between diagnosis and auto-HCT was 7.4 months (range 3.7-143). The ISS stage at diagnosis was available in 54 patients, 24 (39%) of whom had stage 3 disease. Ten out of 44 patients (23%) with available lactic dehydrogenase (LDH) levels at diagnosis had higher than normal levels. Besides the CKS1B gain/amplification, concurrent high-risk cytogenomic markers detected were: monosomy/deletion 13 in 32 (50%), del 17/17p in 8 (12.5%) and del 1p in 7 patients (11%). Fifty-six (88%) patients had received bortezomib-based induction or salvage therapy before auto-HCT. Thirty-five (55%) patients were in 1^st remission while 29 (45%) patients had relapsed disease at auto-HCT. Prior to auto-HCT 3 (5%) patients were in complete remission (CR), 17 (27%) in very good partial remission (VGPR) and 29 (45%) were in partial remission (PR). Seven patients (11%) had progressive disease at auto-HCT. After at least 90 days post auto-HCT, 7 (11%) patients achieved a CR, 24 (37.5%) a VGPR, 20 (31%) a PR, with an overall response rate of 80%. One-hundred-day and 1-year treatment-related mortality were both 0%. After a median follow up of 5.7 moths, 18 (28%) pts had started maintenance treatment, 15 (83%) of these with lenalidomide. Median PFS was 10.7 months and median OS has not yet been reached. Median PFS was 13.3 months for patients transplanted in 1^st remission and 8.3 months for patients transplanted after a relapse (p=0.005). Median OS has not yet been reached whether the patients were transplanted in 1^st remission or after a relapse.

Conclusion: This analysis confirms CKS1B gene gain/amplification as a marker for poor PFS outcomes after stem cell transplantation. Patients with CKS1B gain/amplification are likely to have additional high-risk chromosomal abnormalities, and a shorter PFS whether transplanted in 1^st remission or for relapsed disease.