In multiple myeloma (MM), deletion of TP53/17p (del17p), present in around 10% of patients, is associated with shortened survival. Lower incidence of del17p is reported in African Americans (AA) compared to European Americans (EA), alluding to possible contribution of disease biology to racial differences in outcome among AA and EA patients with MM. Our recent report of a significantly superior age-adjusted risk of death in AA compared to EA patients in the younger (<65) Veteran population also suggests that AA may have a genetic predisposition that renders them to have better therapeutic outcome or have more indolent subtypes of MM. Here we investigated the incidence and impact of del17p on outcome in AA and EA patients with MM at the VA.
We identified 2677 patients with MM from 1999 to 2017 using the VA's nationwide Corporate Data Warehouse for whom information on del17p was available. We extracted data on patients' age, race, ISS stage, therapy at induction and stem-cell transplant (SCT) utilization. Test results for del17p were extracted from lab panel and pathology reports. Our analysis is focused on patients with this data.
Of the 2677 MM patients evaluated for del17p by conventional cytogenetics and/or FISH, self-reported race information was available in 2432 patients, among which AA constituted 35.6% (867) and EA 64.4% (1565). AA had a greater proportion of younger (<65) patients compared to EA (49.48% vs 33.87%, p<0.001). Overall, among those tested, del17p was reported in 7.4% of all patients, but the incidence was significantly lower in AA compared to EA (4.73% vs 8.82%, p<0.001), largely due to the difference in incidence of del17p in younger AA vs EA (3.73% vs 8.30%, p = 0.005). The rates of del17p across different ISS stages were not significantly different, nor did ISS stage differ across race.
As expected, del17p was associated with shortened survival. In the full cohort, median survival was 2.26 years for patients with del17p and 4.27 years for those without (p<0.001). These differences were also observed within race (1.74 vs 4.95 in AA, p<0.001, 2.34 vs 4.13 in EA, p<0.001) and age groups (2.67 vs 5.49 in younger, p<0.001; 2.12 vs 3.5 in older, p<0.001).
We found no significant racial differences in survival between AA and EA patients with del17p deletion (1.74 vs 2.34, p=0.47) regardless of age category. However, importantly we noted a significant racial difference in the median survival between younger AA and EA without del17p (7.75 vs. 4.87 years, p=0.006). In contrast, in older patients without del17p we observed no significant difference in survival across race.
To understand the difference in survival between younger AA and EA without del17p, we compared ISS stage, ECOG status, and novel therapy (bortezomib, lenalidomide, and thalidomide) and SCT utilization between these groups. No significant differences were observed apart from a small difference in utilization of bortezomib in AA patients as compared to EA at induction (63.1% vs 58.3%, p = 0.029). To assess whether bortezomib utilization had any impact on survival, we compared survival among younger AA and EA without del17p after stratifying into three treatment regimens: bortezomib/dex (Vd), lenalidomide/dex (Rd), and RVd. We observed superior survival for AA as compared to EA across all three regimens (Vd: 5.82 vs 3.63 years, p=0.022; Rd: 8.15 vs 5.10, p=0.029; RVd: median not reached vs 6.95, p=0.72), suggesting that the difference in bortezomib utilization was not responsible for the observed difference in survival.
Interestingly, among 198 patients with del17p for whom the percentage of cells with deletion was reported, we observed that higher (>55%) clonality was associated with lower median survival compared to those with low clonality (5-55%) (0.97 vs 2.42, p=0.049). The difference was even more significant with a threshold of 35% (p=0.015).
Our large study identified significantly lower incidence of del17p in younger AA compared to EA. We found no racial disparity in survival among AA and EA with del17p regardless of age. In contrast, in the absence of del17p, younger AA demonstrated significantly better survival as compared to younger EA and better response to bortezomib- and lenalidomide-based doublet and triplet induction regimens, suggesting possible differences in disease biology other than del17p that may contribute to a more indolent course and increased sensitivity to therapy.
Yellapragada:Celgene: Research Funding; Novartis: Employment, Other: Spouse Employment ; BMS: Research Funding; Takeda: Research Funding. Munshi:Takeda: Consultancy; Janssen: Consultancy; Oncopep: Consultancy; Takeda: Consultancy; Oncopep: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Celgene: Consultancy; Amgen: Consultancy; Amgen: Consultancy; Abbvie: Consultancy; Abbvie: Consultancy; Adaptive: Consultancy; Adaptive: Consultancy.
Asterisk with author names denotes non-ASH members.