Age should not be a limiting factor in choosing ASCT

Two articles published in January 2017 address the issue of patient age when choosing Autologous Stem Cell Transplant (ASCT). Dhakal B. et al. from the Division of Hematology/Oncology, Medical College of Wisconsin, USA, published their study in Clinical Lymphoma, Myeloma and Leukemia, and Huang LW et al. from Duke University Medical Center, Durham, NC, USA, published their findings in Hematology Oncology.

Key Findings

Huang LW et al.

• Retrospective study of 340 fit patients (pts) with MM who had undergone ASCT
• Hypothesis: PFS of older patients was non-inferior to that of younger patients after ASCT
• Null hypothesis: PFS hazard ratio (HR) for a 5-year increase in age was ≥1.05; alternative (non-inferiority) hypothesis was that HR was ≤1
• Observed HR = 0.94 (95% confidence interval [CI] 0.86-1.03); null hypothesis rejected since CI upper bound >1.05
• PFS in older patients was at least as good as in younger patients
• Cannot reject analogous null hypothesis for OS: HR = 1.06 (95% CI 0.94-1.19)
• Toxicity similar across ages and transplant-related mortality minimal
• Pts that received maintenance therapy: 28% <65 vs 45% ≥65
• ASCT prolongs PFS equally well in older vs younger adults

Dhakal B et al.

• Compared outcome of 191 pts receiving AHCT (autologous hematopoietic stem cell transplantation) from 2000-2015 in 2 different age groups: >70 years, n = 105 and ≤ 50 years, n = 86
• Primary endpoints: overall survival (OS), progression-free survival (PFS), and non-relapse mortality
• Pts ≤ 50 years had better performance status and lower comorbidity index; most older pts received melphalan (140 to 180 mg/m²)
• Median follow-up: ≤ 50 years = 33 months (range, 2-164 months) vs > 70 years = 22.5 months (range, 3-133 months) (P = 0.02)
• PFS rate at 1 year: ≤ 50 years = 60% (95% CI, 46%-72%); > 70 years = 58% (95% CI, 45%-69%)
• OS rate at 1 year: ≤ 50 years = 92% (95% CI, 84%-96%); > 70 years = 85% (95% CI, 76%-91%)
• Age had no effect on survival with multivariate analysis: P = 0.82
• Pts with high-risk cytogenetics: HR = 2.2 (95% CI, 1.06-4.6; P =0.04) had worse overall mortality
• Worse PFS strongly associated with high-risk cytogenetics: HR = 1.2; 95% CI, 1.1-3.5; P = 0.004; no disease response or progressive disease at transplantation: HR = 5.0; 95% CI, 1.8-13.5; P = 0.02

The conclusion from both studies is that age should not be a limiting factor when considering the modality of AHCT, and that fit and healthy patients of any age could benefit.

Abstract

Huang LW et al.

We retrospectively studied 340 fit patients with multiple myeloma (MM) who underwent autologous stem cell transplantation (ASCT). We hypothesized that progression-free survival (PFS) of older patients was non-inferior to that of younger patients after ASCT. Our null hypothesis was that the PFS hazard ratio (HR) for a 5-year increase in age was ≥1.05; the alternative (non-inferiority) hypothesis was that the HR was ≤1. The observed HR was 0.94 (95% confidence interval [CI] 0.86-1.03); since the CI upper bound was <1.05, we reject the null hypothesis and conclude that PFS in older patients was at least as good as in younger patients. We cannot reject an analogous null hypothesis for overall survival (HR 1.06 [95% CI 0.94-1.19]), since the CI upper bound >1.05. Toxicity was similar across ages and transplant-related mortality was minimal. 28% of subjects <65 versus 45% of those ≥65 received maintenance therapy. In summary, ASCT prolongs PFS equally well in older vs. younger adults. Although we cannot exclude maintenance as a confounder, these data support ASCT for fit seniors with MM.

Abstract 

Dhakal B et al.

Background

In the novel and pre–novel agent era, high-dose therapy, followed by autologous hematopoietic cell transplantation (AHCT), has been shown to prolong survival in patients with multiple myeloma (MM) in randomized trials. However, these trials only included patients aged ≤ 65 years. Given that the median age at diagnosis is 66 years, it is important to know the outcomes of AHCT in older patients. Similarly, definite outcomes of AHCT in very young patients (aged < 50 years) are also lacking because they represent a very small proportion of patients in clinical trials.

Materials and Methods

We analyzed a consecutive cohort of patients with MM receiving AHCT from 2000 to 2015 in 2 different age groups, older (> 70 years) and younger (≤ 50 years), and compared the outcomes. The primary objectives were to assess overall survival, progression-free survival (PFS), and nonrelapse mortality in these 2 groups.

Results

Of the 191 patients, 86 were young (age ≤ 50 years) and 105 were old (age > 70 years). The younger patients had better performance status and a lower comorbidity index, and most of the older patients had received a melphalan dose of 140 to 180 mg/m². The median follow-up period for the young group was 33 months (range, 2-164 months) compared with 22.5 months (range, 3-133 months) in the old group (P = .02). The PFS rate at 1 year was 60% (95% confidence interval [CI], 46%-72%) for the young group and 58% (95% CI, 45%-69%) for the old group. The overall survival rate at 1 year was 92% (95% CI, 84%-96%) for the young group and 85% (95% CI, 76%-91%) for the old group. On multivariate analysis, age did not have any effect on survival (P = .82); however, the patients with high-risk cytogenetics (hazard ratio [HR], 2.2; 95% CI, 1.06-4.6; P = .04) had worse overall mortality. High-risk cytogenetics (HR, 1.2; 95% CI, 1.1-3.5; P = .004) and no disease response or progressive disease at transplantation (HR, 5.0; 95% CI, 1.8-13.5; P = .02) were significantly associated with worse PFS.

Conclusion

Age should not be a limiting factor in considering the modality of AHCT. However, younger patients might also benefit from additional novel treatment approaches in the setting of clinical trials, given their similar outcomes with the older patients in our study.