Intensive Pretransplant Consolidation in Older AML Fails to Improve Results

HOUSTON -- Intensive consolidation treatment before allogeneic stem-cell transplant did not improve outcomes in older patients with acute myeloid leukemia (AML), a retrospective comparison showed.

Relapse-free survival (RFS) at 2 years was virtually identical for patients who received intensive consolidation therapy (51%) and those who did not (50%). The intensive-therapy group had a trend toward worse non-relapse mortality, but the difference did not achieve statistical significance.

Overall survival (OS) and rates of acute and chronic graft versus host disease (GVHD) also did not differ significantly between patients who received intensive or non-intensive pretransplant consolidation therapy, reported Yosr Hicheri, MD, of Institut Paoli Calmettes in Marseilles, France, at the Society of Hematologic Oncology meeting.

The focus should shift to alternative approaches to improve pretransplant status, she suggested, given the negative findings with intensive consolidation therapy. She cited four promising approaches.

"Newer drugs such as FLT3 inhibitors, CPX-351, and inhibitors of IDH have strongly modified the landscape of AML therapeutics," said Hicheri. "Venetoclax [Venclexta] with azacitidine followed by stem-cell transplant in newly diagnosed AML patients older than 60 results in excellent outcomes and likely improves outcomes over maintenance therapy. The development of nonmyeloablative haploidentical stem-cell transplant with peripheral blood cells and post-transplant cyclophosphamide is very well tolerated and leads to long-term survival in elderly patients with AML or MDS [myelodysplastic syndromes]."

A recent retrospective study emphasized the value of allogeneic stem-cell transplantation in older patients with AML. Three different analytic models showed that stem-cell transplantation significantly improved RFS and OS and that patients without transplants continued to relapse over time.

However, few studies have evaluated the role of pretransplant treatment, and results have been mixed, said Hicheri. One study did show that a history of consolidation therapy was associated with improved outcomes in patients who underwent transplant with minimal residual disease-negative status.

To add to the evidence regarding pretransplant therapy, investigators performed a retrospective analysis of patients who underwent allogeneic stem-cell transplant for AML from 2007 to 2017. The analysis was limited to patients older than 60 and in first complete remission (CR).

The analysis involved 130 patients, 68 who received intensive pretransplant consolidation therapy and 62 who received a non-intensive regimen. Patients who received non-intensive therapy were slightly older (66 vs 63), but otherwise the two groups were similar. The primary outcomes were 2-year RFS and OS following stem-cell transplant.

After a median follow-up of 52.2 months, the intensive-therapy group had a 1% absolute increase in RFS, which did not achieve statistical significance (P=0.546). The 2-year non-relapse mortality was 27% with intensive therapy and 16% with non-intensive therapy, although not a significant difference (P=0.564). The 2-year OS favored the non-intensive arm (58% vs 52%), but the difference likewise did not achieve statistical significance (P=0.729).

In a multivariate analysis, cytogenetics emerged as the key prognostic factor for 2-year RFS, which was 56% among patients with favorable or intermediate cytogenetics and 34% for patients with unfavorable cytogenetics (P=0.01). Rates of acute GVHD were 44% with intensive therapy and 50% with non-intensive therapy (P=0.45), and chronic GVHD occurred in 16% versus 12% of the two groups, respectively (P=0.27).

Hicheri acknowledged several limitations of the analysis: missing molecular data for 30% of the patients, lack of information on measurable disease, and no details about post-transplant complications.

Comment