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Intensity of Consolidation Pre-Transplant Shows No Difference in Outcomes in Older AML

No difference in relapse-free survival or non–relapse mortality was seen with intensive vs non-intensive consolidation chemotherapy regimens prior to allogeneic hematopoietic stem cell transplantation in elderly patients over the age of 60 with acute myeloid leukemia in first complete remission.

Consolidation Therapy AML | Image Credit: © Rubbina - stock.adobe.com

Intensity of Consolidation Therapy in AML |

Image Credit: © Rubbina - stock.adobe.com

No difference in relapse-free survival (RFS) or non–relapse mortality (NRM) was seen with intensive vs non-intensive consolidation chemotherapy regimens prior to allogeneic hematopoietic stem cell transplantation in elderly patients over the age of 60 with acute myeloid leukemia (AML) in first complete remission (CR1), according to findings from a retrospective analysis that were presented at the 2023 SOHO Annual Meeting.

At a median follow-up of 52.2 months, the 2-year RFS rate was 51% with intensive therapy vs 50% with non-intensive therapy, showing no difference in outcome between the type of consolidation chemotherapy (P =.546). A trend toward worse NRM was reported with intensive therapy, possibly related to complications such as infections, with a 2-year rate of 27% vs 16% with non-intensive treatment (P =.564). However, the difference was not statistically significant.

“The main takeaway from this study is that there is no impact of intensive vs non-intensive consolidation before hematopoietic stem cell transplantation in AML over 60 years old in CR1,” lead study author Yosr Hicheri, MD, of the Department of Clinical Hematology at the Institut Paoli Clamettes in Marseille, France, said in a presentation of the data. “However, the study does have several limitations, including missing molecular data in nearly one-third of patients, the lack of measurable residual disease, and the absence of detailed analysis of post-transplant complications.”

Prior analyses have shown conflicting data regarding the benefit of intensive vs non-intensive consolidation in elderly populations, Hicheri explained. As such, investigators set out to conduct a retrospective analysis over 10 years, from 2007 and 201, using the institution’s local Allograft database. Investigators included 130 patients over the age of 60 years in CR1 who underwent allogeneic stem cell transplant. A total of 68 patients had received non-intensive therapy consisting of low-dose cytarabine or azacytidine and 62 had received intermediate- or high-dose cytarabine.

Regarding baseline characteristics, the median overall age at transplant was 64 years (range, 60-72). Most patients had de novo AML (78%) as compared with secondary AML (22%). Most patients had intermediate- (38%) or adverse-risk (30%) disease per European LeukemiaNet 2017 criteria; 6% and 26% of patients had favorable risk and missing data, respectively. Most patients (73%) had undergone transplant within 6 months of diagnosis and had received matched unrelated donor/mismatched unrelated donor (42%) or sibling (37%) donor transplant. Conditioning regimens were largely reduced intensity (70%) or myeloablative (30%).

Additional results indicated that there was no difference in overall survival between the 2 cohorts, with 2-year rates of 52% with intensive therapy vs 58% with non-intensive therapy (P =.729).

In a multivariate analysis, unfavorable cytogenetic risk was associated with worse RFS, with a 2-year rate of 34% compared with 56% in patients with intermediate or favorable cytogenetic risk (P =.01).

Moreover, no difference in the rate of graft-vs-host-disease (GVHD) was reported based on consolidation regimen. Acute GVHD occurred in 44% of patients who received intensive therapy vs 50% of those who received non-intensive treatment (P =.45). Chronic GVHD occurred less frequently but at similar incidence between the intensive and non-intensive cohorts (16% vs 12%, respectively; P =.27).

“We now know that there’s no benefit of intensive chemotherapy. New drugs such as FLT3 inhibitors, CPX-351 [Vyxeos], and inhibitors of IDH have strongly modified the landscape of AML therapeutics. Venetoclax [Venclexta] [plus] azacytidine followed by stem cell transplant results in an excellent outcome and likely improves outcome over maintenance therapy in newly diagnosed AML patients older than 60,” Hicheri stated. “The development of nonmyeloablative haploidentical stem cell transplant with peripheral blood cell and post-transplant cyclophosphamide is [also] very well tolerated and allowed long-term survival in elderly patients with AML or myelodysplastic syndrome. [We] now have 4 powerful tools for maintenance therapy after allogeneic stem cell transplant to maintain response.”

Hicheri concluded by highlighting an ongoing phase 2 study (NCT04968015) in which elderly patients with AML in CR1 following treatment with idarubicin, cytarabine, and lomustine will be randomly assigned to 6, 28-day cycles of treatment with venetoclax plus cytarabine or idarubicin and cytarabine. The primary end point is 2-year RFS, and patients will be followed for a period of 5 years.

Reference

Hicheri Y. Impact of consolidation chemotherapy intensity before allogeneic hematopoietic stem cell transplantation in elderly patients with acute myeloid leukemia. Presented at: Society of Hematologic Oncology 2023 Annual Meeting; September 6-9, 2023; Houston, TX.

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