Contributions
Abstract: S242
Type: Oral Presentation
Session title: Stem cell transplantation - Clinical
Background
Relapse remains the main cause of treatment failure after allogeneic stem cell transplantation (HSCT) for acute myeloid leukemia (AML) in first complete remission (CR1). The antileukemic activity of myeloablative conditioning is often counterbalanced by an age-dependent increase in non-relapse mortality (NRM). For AML patients >40 years, fludarabine plus a reduced dose of TBI (8Gy) (FluTBI) has yielded favorable long-term outcomes (CIR 30%, NRM 13%; Fasslrinner F et al., Lancet Haematology 2018). Similar data have been obtained with flu plus treosulfan (FT), which is being increasingly used due to its low NRM (Beelen DW et al., Lancet Haematology 2020).
Aims
As no direct comparison of these two conditioning regimens has yet been conducted, we assessed antileukemic activity and safety of FluTBI and FT (30, 36 or 42 mg/m2) in patients with AML transplanted in CR1.
Methods
This retrospective analysis of data from the EBMT registry included 754 AML (617 FT, 137 FluTBI) patients aged >40 years who underwent a first HSCT in CR1 from 2009-2019. Allografts were from matched siblings (MSD) or 10/10 HLA-matched unrelated donors (MUD). Using propensity score matching, 115 FluTBI patients were pair-matched with 115 FT (exact matching for donor, sAML, adverse cytogenetics and nearest neighbor for age, time diagnosis-HSCT, female to male, Karnofsky performance score (KPS) and in vivo T cell depletion).
Results
Patient characteristics were well balanced in the FluTBI and FT groups with respect to age (median 55.2 [40.1-70.7] vs 54.9 [40.4-74.9] years, KPS <90% (22.6 vs 23.5%), sAML (13% each), adverse cytogenetics (15.7% each), female donor to male recipient (19.1% vs 17.4%) and time from diagnosis to HSCT (median 3.8 (range, 1.8-16.2) vs 4.5 (1.7-16.2) months). An identical proportion of patients in both groups received grafts from MSD (61.7%) and MUD (38.3%). Graft versus host disease (GVHD) prophylaxis was predominantly cyclosporine A (CSA) and methotrexate (85.2 vs 73.9%) or CSA and mycophenolate mofetil (8.7 vs 18.3%), respectively. Additional in vivo T cell depletion with ATG was given in 52.2% and 53.9% of patients, respectively. Median follow-up is 42.4 months (range, 31.5-53.8) in the FluTBI and 23.2 months (20.4-32.7) in the FT group (p=0.14). All but one patient in each group engrafted. FluTBI was associated with a significantly lower relapse incidence (CIR) of 18.3 vs 34.7%, p=0.018, HR 0.51 (95% CI, 0.29-0.89), but higher NRM of 16.8 vs 5.3%, p=0.02, HR 3.0 (1.19-7.59). Infection was the leading cause of death following FluTBI (n=12/38, 31.6%), followed by AML (10/26.3%), GVHD (6/15.7%), interstitial pneumonia (4/10.5%) and secondary malignancy (2/5.3%). In the FT group, 33 patients died, 15 from AML (45.5%), 7 from GVHD (21.2%), and 3 from infection or multiorgan failure (9.1% each), respectively. There was no statistically significant difference between FluTBI and FT in the CI of acute GVHD II-IV (22.8 vs 20.7%; HR 1.05), GVHD III-IV (6.2 vs 9.0%; HR 0.59), chronic GvHD (42.6 vs 47.5%; HR 0.81) or extensive chronic GVHD (16.8 vs 19.6%; HR 0.76). At 2 years, leukemia-free and overall survival were similar in the FluTBI and FT groups (64.9 vs 60.0%, HR 0.84 (0.54-1.31) and 66.9 vs 67.8%, HR 1.08 (0.67-1.75), respectively, with favorable GVHD-free and relapse-free survival in both groups (50.3 vs 45.6%; HR 0.83 [0.58-1.17]).
Conclusion
Outcomes in LFS, OS and GRFS did not differ between FluTBI and FT. Relapse was lower while NRM higher with FluTBI which may indicate a more intense conditioning.
Keyword(s): AML, Conditioning, Stem cell transplant, Total body irradiation
Abstract: S242
Type: Oral Presentation
Session title: Stem cell transplantation - Clinical
Background
Relapse remains the main cause of treatment failure after allogeneic stem cell transplantation (HSCT) for acute myeloid leukemia (AML) in first complete remission (CR1). The antileukemic activity of myeloablative conditioning is often counterbalanced by an age-dependent increase in non-relapse mortality (NRM). For AML patients >40 years, fludarabine plus a reduced dose of TBI (8Gy) (FluTBI) has yielded favorable long-term outcomes (CIR 30%, NRM 13%; Fasslrinner F et al., Lancet Haematology 2018). Similar data have been obtained with flu plus treosulfan (FT), which is being increasingly used due to its low NRM (Beelen DW et al., Lancet Haematology 2020).
Aims
As no direct comparison of these two conditioning regimens has yet been conducted, we assessed antileukemic activity and safety of FluTBI and FT (30, 36 or 42 mg/m2) in patients with AML transplanted in CR1.
Methods
This retrospective analysis of data from the EBMT registry included 754 AML (617 FT, 137 FluTBI) patients aged >40 years who underwent a first HSCT in CR1 from 2009-2019. Allografts were from matched siblings (MSD) or 10/10 HLA-matched unrelated donors (MUD). Using propensity score matching, 115 FluTBI patients were pair-matched with 115 FT (exact matching for donor, sAML, adverse cytogenetics and nearest neighbor for age, time diagnosis-HSCT, female to male, Karnofsky performance score (KPS) and in vivo T cell depletion).
Results
Patient characteristics were well balanced in the FluTBI and FT groups with respect to age (median 55.2 [40.1-70.7] vs 54.9 [40.4-74.9] years, KPS <90% (22.6 vs 23.5%), sAML (13% each), adverse cytogenetics (15.7% each), female donor to male recipient (19.1% vs 17.4%) and time from diagnosis to HSCT (median 3.8 (range, 1.8-16.2) vs 4.5 (1.7-16.2) months). An identical proportion of patients in both groups received grafts from MSD (61.7%) and MUD (38.3%). Graft versus host disease (GVHD) prophylaxis was predominantly cyclosporine A (CSA) and methotrexate (85.2 vs 73.9%) or CSA and mycophenolate mofetil (8.7 vs 18.3%), respectively. Additional in vivo T cell depletion with ATG was given in 52.2% and 53.9% of patients, respectively. Median follow-up is 42.4 months (range, 31.5-53.8) in the FluTBI and 23.2 months (20.4-32.7) in the FT group (p=0.14). All but one patient in each group engrafted. FluTBI was associated with a significantly lower relapse incidence (CIR) of 18.3 vs 34.7%, p=0.018, HR 0.51 (95% CI, 0.29-0.89), but higher NRM of 16.8 vs 5.3%, p=0.02, HR 3.0 (1.19-7.59). Infection was the leading cause of death following FluTBI (n=12/38, 31.6%), followed by AML (10/26.3%), GVHD (6/15.7%), interstitial pneumonia (4/10.5%) and secondary malignancy (2/5.3%). In the FT group, 33 patients died, 15 from AML (45.5%), 7 from GVHD (21.2%), and 3 from infection or multiorgan failure (9.1% each), respectively. There was no statistically significant difference between FluTBI and FT in the CI of acute GVHD II-IV (22.8 vs 20.7%; HR 1.05), GVHD III-IV (6.2 vs 9.0%; HR 0.59), chronic GvHD (42.6 vs 47.5%; HR 0.81) or extensive chronic GVHD (16.8 vs 19.6%; HR 0.76). At 2 years, leukemia-free and overall survival were similar in the FluTBI and FT groups (64.9 vs 60.0%, HR 0.84 (0.54-1.31) and 66.9 vs 67.8%, HR 1.08 (0.67-1.75), respectively, with favorable GVHD-free and relapse-free survival in both groups (50.3 vs 45.6%; HR 0.83 [0.58-1.17]).
Conclusion
Outcomes in LFS, OS and GRFS did not differ between FluTBI and FT. Relapse was lower while NRM higher with FluTBI which may indicate a more intense conditioning.
Keyword(s): AML, Conditioning, Stem cell transplant, Total body irradiation