Allogeneic Hematopoietic Stem Cell Transplantation in Older Patients with Acute Myeloid Leukemia: Analysis of Outcomes and Contemporary Trends Spanning 10 Years

Abstract

Background: Allogeneic hematopoietic stem cell transplantation (SCT) is a highly effective consolidation strategy in acute myeloid leukemia (AML). Non-myeloablative and reduced-intensity (NMA/RIC) conditioning regimens have expanded the use of SCT to older patients (pts) (age ≥ 60 years). Age alone no longer appears to be a barrier for successful SCT, with reported 3-year overall survival (OS) rates in the 45-50% range (Maakaron 2022). Methods: We conducted a retrospective study spanning 10 years to evaluate SCT-related outcomes in older AML. All pts ≥ 60 years presenting to our institution with newly-diagnosed (ND) AML were included. Acute promyelocytic leukemia (APL) was excluded. Median OS and relapse-free survival (RFS) were calculated using the Kaplan Meier method. A landmark analysis was performed to evaluate time-to-event endpoints in pts who underwent SCT in first response compared to those who did not. Results: Between 7/19/2012 and 11/17/2021, we identified 1073 pts ≥ 60 years with ND-AML. The median age at diagnosis was 71 years (range 60-94), 622 (58%) were male, 189 (18%) had prior myelodysplastic/myeloproliferative neoplasm, and 220 (21%) had therapy-related AML. ELN 2017 risk was favorable in 215 (20%), intermediate in 234 (22%), and adverse in 538 (50%) pts (86 with data missing). Most pts (84%) were treated with low-intensity (LOW) regimens. Only 16% were treated with intensive (INT) chemotherapy (intermediate or higher dose cytarabine). Venetoclax (VEN) was included in 34% of the regimens. The CR/CRi rate was 60% in the overall cohort. The CR/CRi rate was 74%, 48%, and 72% in pts treated with INT, LOW, and LOW + VEN therapies, respectively. The median OS and RFS were 11.2 and 10.6 months for the full cohort, respectively. The rate of referral to the SCT service was 38% (413/1073) and increased over time (31% in 2012-2013, 52% by 2020-2021). This occurred in parallel to increasing rates of CR/CRi (53% in 2012-2013, 66% by 2020-2021), likely reflecting increased efficacy of VEN-containing regimens in the later years. We identified 198/1073 pts (18%) who underwent SCT at some point during therapy, 152/198 (77%) in first response (CR/CRi/MLFS) after frontline therapy, and 46/198 (23%) following one or more salvage regimens. Of all ND-AML pts, the SCT rate was 37%, 10%, and 22% in pts treated with INT, LOW, and LOW + VEN, respectively. The rate of undergoing SCT increased over time (15% in 2012-2013, 27% by 2020-2021). Clinical/SCT characteristics for the pts who underwent SCT are shown in table 1. The rate of grade 3/4 acute graft-vs-host disease (GVHD) was 11% and 19% of pts experienced chronic GVHD of any grade. Following SCT, 24% of pts experienced relapse of AML and 21% died without disease relapse. The 100-day mortality following SCT was 13%. We then performed a landmark analysis (using median time to SCT [4.3 months] as the landmark) comparing pts undergoing SCT in first response following frontline therapy at our institution (n=139) to responding pts who did not receive SCT in first response and who were alive and without relapse at the landmark (n=353). Both the median OS (31.0 vs 18.9 months, p=0.0208, figure 1) and median RFS (23.2 vs 10.0 months, p<0.0001) were superior in the pts who underwent SCT compared to those who did not. Pts undergoing SCT in first response were younger (median age 66 vs 72 yrs) and had better performance status (PS 2-4 in 10% vs 22%) compared to no-SCT pts. Distribution of ELN risk categories and best response (CR/CRi/MLFS) were similar in the SCT and no-SCT groups. In pts who responded to initial therapy and were referred for SCT, but ultimately did not undergo SCT in first response (n=161), the most common documented reasons for forgoing SCT were social reasons (pt preference, financial/insurance/caregiver issues) in 29%, disease relapse in 29%, being deemed unfit due to comorbidities in 22%, active uncontrolled infections in 11%, and other reasons in 11%. An adequate donor was documented in 66% of these pts. Conclusions: Our results support the use of SCT as a consolidative strategy in older AML pts. Pts who undergo SCT have superior OS and RFS compared to those who do not. However, fewer than 20% of pts undergo the procedure mostly due to inadequate disease control, comorbidities, and a variety of social reasons. Recent trends indicate higher rates of SCT referral and completion as more effective anti-leukemic therapies are allowing a greater proportion of older AML pts to undergo SCT. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal