Clinical Outcomes of Multiple Myeloma Patients with TP53 Gene Deletion after Autologous Stem Cell Transplantation: The MD Anderson Cancer Center Experience

Introduction

 Deletion of TP53 gene mapped to 17p13, which can be identified by conventional cytogenetics or fluorescent in situ hybridization (FISH), is associated with poor outcome in multiple myeloma (MM), even after the introduction of novel agents and the use of high-dose chemotherapy and autologous (auto) or allogeneic (allo) hematopoietic stem cell transplantation (HCT). Here we report the outcomes of patients (pts) with TP53 deletion (del) on FISH studies who underwent an auto- or allo-HCT at our institution.

Methods

We identified 39 pts with MM who had TP53 del on FISH studies prior to HCT at our institution between 2008 and 2014, and compared their outcomes to a matched control group (CG) (n=117) without TP53 del who were treated during the same time period. Matching was based on age and response to the last therapy prior to HCT.

Results

Patient characteristics are summarized in the attached Table. The ISS stage at diagnosis was available for 27 pts in the TP53 group (TP53 Grp), 52% of whom had stage III disease. Most pts in the TP53 Grp had received a proteasome inhibitor (PI) (95%) or an immune modulatory agent (IMiD) (72%) prior to HCT. The response to last therapy was either stable or progressive disease in 36% of patients in both groups. The median follow-up intervals were 16 and 26 months (m) for the TP53 Grp and CG, respectively. The median overall survival (OS) in the TP53 Grp was 21 m vs 57 m in the CG; 2-year OS in the TP53 Grp was 46% vs 86% in the CG (both, P< 0.001). Median progression-free survival (PFS) in the TP53 Grp was 8.5 m vs 28 m in the CG; 2-year PFS in the TP53 Grp was 18% vs 56% in the CG (both, P< 0.001). Three of the five pts in the TP53 Grp who received an allo-HCT relapsed post-HCT, and none died of non-relapse causes. In the TP53 Grp, univariate analysis identified a trend toward a higher risk of disease progression in pts who underwent HCT with relapsed disease (HR=2.4, 95% CI 0.99-5.8, P=0.053). Otherwise, age, response prior to HCT, time from diagnosis to HCT, ISS stage, allo vs auto HCT, conditioning regimen, cytogenetics, and prior exposure to PI or IMiD were all non-significant factors. On multivariate analysis for the entire cohort, p53 del (HR=3.2, 95% CI 1.9-5.3, P<0.001) and relapsed disease at HCT (HR 2.2, 95% CI 1.3-3.6, P=0.002) were independent factors associated with a higher risk of early progression.

Conclusions

In the era of PI, IMiD, and HCT, TP53 del remains a poor prognostic factor in MM. Relapsed disease at the time of HCT was associated with a higher risk of progression. Novel approaches and perhaps early allogeneic HCT require evaluation in this high-risk population.

	TP53 Grp	CG
Median age, years (range)	58 (34-69)	58 (31-79)
Sex (M/F)	24/15	62/55
Disease Status at time of HCT, %
Relapse	64	42
Other	36	58
HCT Type, %
Auto	87	97
Allo	13	3
Diagnosis to HCT >12 months, %	46	42
Maintenance therapy, %	59	62