Intensive Chemotherapy Group Research Articles

Efficacy of haploidentical allogeneic hematopoietic cell transplantation following two courses of venetoclax and azacytidine therapy in patients over 55 years old with acute myelogenous leukemia.

The combination of venetoclax (VEN) and azacytidine (AZA) has demonstrated potential in achieving rapid and effective remissions in elderly patients with acute myeloid leukemia (AML). Allogeneic hematopoietic stem cell transplantation is a promising potential cure for high-risk AML, as VEN-based therapies have a worse prognosis in elderly patients. This study aimed to assess the efficacy of sequential haploidentical HSCT following two courses of VEN and AZA therapy in patients with AML aged 55 years and older. We conducted a retrospective study on AML patients aged 55 to 70 years who received intensive chemotherapy or two courses of VEN/AZA therapy, followed by haplo-HSCT based on disease risk degree, measurable residual disease status and patient's preference. Between January 2019 and December 2023, 141 newly diagnosed AML patients received initial treatment with intensive chemotherapy or VEN/AZA therapy. Among them, 64 patients received haplo-HSCT, while 77 did not. The 1-year over survival (OS) and relapse-free survival (RFS) of patients who received haplo-HSCT were significantly higher than those who did not receive haplo-HSCT (P<0.05). Among patients who received transplantation, there was no significant difference in 1-year OS and RFS between the VEN/AZA and intensive chemotherapy groups: 76.3% vs 69.3% (P = 0.367) for OS, and 74.5% vs 69.7% (P = 0.473) for RFS. High-risk ELN stratification and the presence of ≥4 gene mutations were associated with lower OS and RFS in both univariate and multivariate analysis. AML patients over 55 years of age who received haplo-HSCT after two courses of VEN/AZA therapy had outcomes similar to those who received haplo-HSCT after intensive chemotherapy, suggesting that two courses of VEN/AZA therapy as a bridge to halpo-HSCT are feasible for patients over 55 years old.

Analysis of Treatment Patterns and Outcomes in Patients Ages 60-74 in the Post-Venetoclax Era

Introduction Clear standards of care exist for patients with AML under the age of 60 who are eligible for intensive chemotherapy (IC), as well as for patients over the age of 75 or who are unfit for IC. Fit patients between the ages of 60-74 have historically been understudied, but have lower rates of remission and increased rates of toxicity with intensive regimens compared to younger individuals with AML. We sought to evaluate treatment patterns and outcomes in this patient group. Methods We performed a single-center, retrospective analysis of consecutive patients ages 60 through 74 years at the time of their AML diagnosis who received frontline therapy between April 2018 and September 2022. Low intensity therapy (LIT) regimens included combinations of a hypomethylating agent, low dose cytarabine, venetoclax, cladribine, and/or targeted agents. IC regimens included an anthracycline and higher-dose cytarabine-based regimens (≥1g/m 2) +/- targeted agents. Clinical and genomic data including patient demographics, laboratory results including bone marrow pathology and mutational data, treatment responses, and allogeneic hematopoietic stem cell transplantation (HCT) data including conditioning regimen and donor type (when applicable) were abstracted from the medical record. Minimal residual disease (MRD) status was assessed by multi-parameter flow cytometry with a sensitivity of 0.02%. The statistical analysis was performed using R 1. Results 143 patients were included in the analysis; 47 (33%) received front line IC, and 96 (67%) received LIT. Baseline characteristics are shown in Table 1. Patients receiving IC were younger, more likely to be female, and more likely to have a favorable ELN risk stratification 2, but otherwise balanced. The percentage of patients receiving IC remained the same in each calendar year. Patients in the IC and LIT groups had similar rates of complete remission (CR; 70% vs 70%, respectively, p = 0.96). Among those achieving CR, 22 (67%) patients in the IC group achieved MRD-negativity vs. 35 (52%) in the LIT group (p = 0.17). The median duration of remission was 9 months in the IC group and 12 months in the LIT group (p = 0.17). The median overall survival (OS) was 17 months for IC and 15 months for LIT (p = 0.16). For patients harboring FLT3-ITD, IDH1, IDH2, or TP53 mutations, there was no difference in OS based on receipt of either IC or LIT, nor was there any difference in OS according to ELN 2022 risk category. A significantly higher proportion of patients who received IC underwent HCT (68% vs 42%, p = 0.003). In both groups, OS was significantly longer for patients who received HCT. Treatment-related mortality (TRM) was comparable in each group, with 5 (11%) and 8 (8%) deaths in IC vs. LIT, respectively. The median number of days hospitalized within the first 60 days after induction therapy was notably different at 32 days for IC and 5.5 days for LIT (p < 0.00001), with 34 (35%) LIT patients who had 0 days of hospitalization post-induction compared to IC patients who universally were hospitalized as part of their induction treatment plan. Conclusion In our cohort, patients with AML between the ages of 60-74 had comparable rates of CR, MRD negativity, duration of response, and overall survival whether treated with IC or LIT, with no difference when stratified by mutational status or ELN risk. Intensively-treated patients were younger and more likely to receive HCT but both groups had an OS benefit from HCT. Our data suggest that in the era of novel agents such as venetoclax, less intensive induction strategies may be appropriate for IC-eligible patients between the ages of 60-74. References 1R Core Team (2021). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. https://www.R-project.org/. 2Döhner H, Wei AH, Appelbaum FR, Craddock C, DiNardo CD, Dombret H, Ebert BL, Fenaux P, Godley LA, Hasserjian RP, Larson RA, Levine RL, Miyazaki Y, Niederwieser D, Ossenkoppele G, Röllig C, Sierra J, Stein EM, Tallman MS, Tien HF, Wang J, Wierzbowska A, Löwenberg B. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood. 2022 Sep 22;140(12):1345-1377. doi: 10.1182/blood.2022016867. PMID: 35797463.

Real-World Comparison of Venetoclax-Based Treatment Versus Intensive Chemotherapy As Bridging to Allogeneic Stem Cell Transplantation in MDS-IB2 Patients

Background Allogeneic stem cell transplantation (alloSCT) is the cornerstone therapy for myelodysplastic syndromes with increased blasts-2 (MDS-IB2). However, the optimal induction therapy before transplantation remains unclear. Herein, we compared our single-center experience of non-intensive Venetoclax (Ven)-based regimens versus standard intensive chemotherapy (IC) as bridging to alloSCT in MDS-IB2 patients. Methods We have performed an observational, retrospective, single-center study. All patients were at least 18 years of age, had newly diagnosed, previously untreated MDS-IB2 based on the 5 th edition of the WHO diagnostic criteria, were considered transplant-eligible at diagnosis, and had received either Ven-based therapies or IC for induction. All patients provided informed consent for data collection. The Ven-based regimens were either Ven14+Aza7 (Venetoclax 400mg/d on days 1-14 with Azacitidine 75mg/m 2 on days 1-7) or ACTIVE (Venetoclax 600mg/d on days 1-14, Cytarabine 20mg/m 2 on days 1-10 and Actinomycin D 12.5mcg/kg on days 1-3). IC regimens were 7+3 or FLAG-Ida. After 1 or 2 cycles of induction therapy transplant-eligible responders proceeded to alloSCT. We evaluated baseline characteristics, IPSS-M, IPPS-R values, CR, CRh and marrow CR (mCR) rates, time to ANC>1x10 9 and PLT>100x10 9 recovery, CTCAE v5.0 grade 3-5 non-hematological adverse events, overall survival (OS) and day-30 mortality. Results Detailed baseline characteristics are summarized in Table 1. 18 patients (13 female) had received Ven-based therapies and 15 patients (7 female) had undergone IC. The median age was 59 (27-71) in comparison to 56 (24-66) in Ven and IC patients, respectively (p=0.104). The median ECOG value was 1 (0-2) in the Ven group and was significantly higher compared to 0 (0-2) in the IC cohort (p=0.042). The median IPSS-R and IPSS-M values were 6.5 (5.5-10) and 2.19 (0.78-4.73) compared to 7.25 (4.5-10) and 3.15 (0.93-4.52) in Ven and IC patients, respectively (p=0.746, p=0.79). The mCR rate was 82% in Ven patients compared to 87% in the IC group (p=0.741). The CR+CRh rates were 59% and 73% in Ven and IC groups, respectively (p=0.396). Sixty-three percent of Ven patients were allotransplanted compared to 73% in the IC group (p=0.526). Grade 3-5 non-hematological toxicity was lower in the Ven group compared to the IC patients (44% vs 87%, p=0.013). The median times to neutrophil and platelet recovery were 44 (4-165) and 34 (21-94) days compared to 30 (21-110) and 32 (21-36) days in the Ven and IC groups, respectively (p=0.285, p=0.775). The median OS was 15.1 months (3.2-22.1) and 13 months (6.7-40.3) in the Ven and IC groups, respectively (p=0.637). Survival data are shown in Figure 1. The day-30 mortality rate was 11% in the Ven group compared to 7% in the IC patients (p=0.663). Conclusions We did not observe significant differences between low-intensity Ven-based regimens and IC in terms of responses, overall survival, and number of transplanted patients in this high-risk MDS-IB2 cohort. Non-hematological grade 3-5 toxicity was lower in Ven-treated patients. Our real-life, single-center results should be interpreted with caution.

Outpatient Low-Dose Venetoclax Plus Azacitidine Vs. Intensive Chemotherapy for Newly Diagnosed Fit Patients with Acute Myeloid Leukemia in a Limited Resource Setting

Introduction: venetoclax plus azacitidine (Ven/Aza) is the standard-of-care in patients with newly diagnosed acute myeloid leukemia (AML) who are unsuitable candidates for intensive chemotherapy (IC), prompting questions related to whether it should be used for candidates fit for IC (FIT). Access to novel agents in low- and middle-income countries (LMIC) is limited, however, in a previous phase 2 study (NCT05048615), we demonstrated that using venetoclax concomitantly with strong CYP3A4 inhibitors like itraconazole could be a practical approach to reduce the venetoclax dose and diminish treatment-related costs without compromising treatment response. We sought to compare FIT patients for IC with newly diagnosed AML who received either low-dose Ven/Aza or traditional IC as first-line treatment to evaluate survival outcomes in LMIC. Methods: we retrospectively included all newly diagnosed adult patients with AML suitable for IC treated in our center from August 2016 to March 2023. Since the COVID-19 pandemic, we have used Ven/Aza as a standard first-line therapy in an effort to reduce early mortality and to allow outpatient induction for all patients with AML. Low-dose Ven/Aza was administered as follows: venetoclax 100 mg QD fixed dose plus itraconazole 100 mg BID for 21 days per cycle, and azacitidine 100 mg SC fixed dose QD or 7 days, 1-2 cycles. IC patients received 7+3 or intermediate dose cytarabine plus 3 days of mitoxantrone. Consolidation with intermediate dose cytarabine was given following remission in both groups. Baseline characteristics were registered and compared. We evaluated induction complications, complete response (CR/CRi), 30 and 60-day early death (ED), allogeneic hematopoietic stem cell transplantation (HCT), event-free survival (EFS), and overall survival (OS). Multivariate Cox regression for OS was performed. Results: 83 patients were included, the median age at diagnosis was 44 years (IQR, 32-56), 27 received Ven/Aza (56% received 2 cycles), and 56 IC. Patients who received Ven/Aza were older, had a higher risk disease, and had a longer time between diagnosis and treatment. Patients who received Ven/Aza had a lower incidence of febrile neutropenia, need for transfusions, and less than half required hospitalization during induction; 30- and 60-day mortality was reduced 2.4 and 3-fold in Ven/Aza vs IC although statistical significance was not reached. There were no differences in the rate of CR/CRi between groups (Table 1). After achieving CR/CRi, the IC group had a higher incidence of being relapsed however the median EFS was not different with 7.7 months (95% CI 5.9-9.6) for Ven/Aza vs. 8.5 months (95% CI 6.6-10.5) for IC (p=0.53). Median OS was 10 months (95% CI 5.8-14.1) for Ven/Aza vs 9 months for IC (95% CI 6.6-11.3) (p=0.33) (Figure 1). Patients who received Ven/Aza followed by HCT had the best outcomes with a 2-year OS of 80% vs. 35.5% of those who received IC plus HCT. An OS landmark analysis for patients alive at or beyond 5 months (median time from diagnosis to HCT) showed prolonged survival in HCT vs. not transplanted patients (16 vs 11 months, p=0.035), irrespective of their induction arm. In the multivariate analysis, HCT (HR 0.05, 95% CI 0.007-0.5) and a need for cytoreduction (HR 8.7, 95% CI 1.2-59.6) were the only predictors of OS. Conclusion: in this single-center study, AML patients treated in a limited resource setting with low-dose Ven/Aza had similar complete response and survival to IC with reduced complications and shorter hospital stay, despite being older with higher risk disease. This induction treatment is a low-cost but effective option in a LMIC environment and could be considered an alternative option, even in suitable candidates for IC, especially with access to HCT.

Prognostic value of European LeukemiaNet 2022 criteria and genomic clusters using machine learning in older adults with acute myeloid leukemia.

This study aimed to validate the new European Leukemia Net (ELN) 2022 criteria for genetic risk stratification in older adults with acute myeloid leukemia (AML) and to determine the most likely set of clusters of similar cytogenetic and mutation properties correlated with survival outcomes in three treatment groups: intensive chemotherapy (IC), hypomethylating agents (HMA) alone, and HMA plus venetoclax (HMA/VEN). The study included 279 patients (aged ≥60 years) who received IC (N=131), HMA (N=76), and HMA/VEN (N=72) between July 2017 and October 2021. No significant differences were observed in survival among the groups according to ELN 2022 risk stratification. Unsupervised hierarchical clustering analysis identified nine genomic clusters (C1-9) with varying survival outcomes depending on treatment type. For example, C4 (predominant for core binding factor-AML) displayed a favorable prognosis in the IC group, but not in the HMA or HMA/VEN groups. The HMA/VEN group had better outcomes than the HMA group in many clusters (C1, 2, 3, and 5); however, the addition of VEN to HMA or IC did not improve the survival outcomes compared with those of HMA alone in C7 and C9 (predominant for -5, del(5q), -7, -17/abn(17p), complex karyotypes, and mutated TP53). The study highlights the limitations of ELN genetic risk stratification in older adults with AML. It emphasizes the need for a more comprehensive approach that considers co-occurring somatic mutations to guide treatment selection in older adults with AML.

Clinical outcome of therapy-related acute myeloid leukemia patients. Real-life experience in a University Hospital and a Cancer Center in France.

t-AML occurs after a primary malignancy treatment and retains a poor prognosis. To determine the impact of primary malignancies, therapeutic strategies, and prognostic factors on clinical outcomes of t-AML. A total of 112 adult patients were included in this study. Fifty-Five patients received intensive chemotherapy (IC), 33 non-IC, and 24 best supportive care. At t-AML diagnosis, 42% and 44% of patients presented an unfavorable karyotype and unfavorable 2010 ELN risk profile, respectively. Among treated patients (n = 88), 43 (49%) achieved complete remission: four out of 33 (12%) and 39 out of 55 (71%) in non-IC and IC groups, respectively. With a median follow-up of 5.5 months, the median overall survival (OS) and disease-free survival (DFS) for the whole population were 9 months and 6.3 months, respectively, and for the 88 treated patients 13.5 months and 8.2 months, respectively. Univariate analysis on OS and DFS showed a significant impact of high white blood cells (WBC) and blast counts at diagnosis, unfavorable karyotype and ELN classification. Multivariate analysis showed a negative impact of WBC count at diagnosis and a positive impact of chemotherapy on OS and DFS in the whole population. It also showed a negative impact of previous auto-HCT and high WBC count on OS and DFS and of IC on OS in treated patients which disappeared when we considered only confounding variables (age, previous cancers, marrow blasts, and 2010 ELN classification). In a pair-matched analysis comparing IC treated t-AML with de novo AML, there was no difference of OS and DFS between the two populations. We showed, in this study that t-AML patients with unfavorable features represented almost half of the population. Best outcomes obtained in patients receiving IC must be balanced by known confounding variables and should be improved by using new innovative agents and therapeutic strategies.

Prognostic Value of Genomic Clusters Using Machine Learning in Older Adults with AML

Background: Older adults with AML have a decline in performance statues and acquired comorbidities compared to younger patients. Treatment intensity and outcomes were varied according to those factors. Various studies tried to classify genetic landscapes to predict outcomes in AML patients. However, those were mostly for younger patients treated with intensive chemotherapy. Machine learning (ML) is useful for classifying large data by calculating each data and subtracting characteristics. Given the limited data of genomic classification for older adults with AML, we analyzed genetic landscapes using ML in the context of treatment intensity. Methods: Unsupervised hierarchical clustering method was used to determine the most likely set of clusters according to cytogenetic/mutation properties at AML diagnosis. Patient selection criterion for this analysis were set as follows; (a) elderly (60 years or older) AML patients who were diagnosed in Seoul St. Mary's Hospital between Jul 2017 and Oct 2021, (b) having available information on chromosome and gene mutation at diagnosis and (c) treated with either intensive chemotherapy (IC), hypomethylating agents (HMA), or HMA plus Venetoclax (HMA/VEN). Patients who received best supportive care only were not included in this study. Results: A total of 279 patients who met inclusion criteria were selected and their median age at diagnosis was 68 years (range 60-). As first-line treatment, 131 patients received IC (47.0%), 76 patients received HMA only (27.2%), and 72 patients were treated with HMA/VEN (25.8%). After a median follow up of 22.5 months, the median overall survival (OS) in the three groups were 22.7, 8.8, and 12.0 months, respectively (p<0.001). We applied the ELN2022 risk stratification to these 3 different treatment groups. For IC group, there was no survival difference between favorable, intermediate, and adverse groups (44 months, 23.1 months, 14.9 months p=0.255). In addition, HMA groups (p-value =0.903) and HMA/VEN group (p-value = 0.805) did not showed survival differences according to risk groups by ELN2022. Next, we conducted hierarchical clustering analysis in a total cohort, which was found to be best classified into 8 clusters by indices for determining the number of clusters. The dominant cytogenetic features of each cluster are demonstrated as follows. The cluster 1(C1) was a group that IDH1 and TP53 mutations were mostly proportioned; C2 was RNA splicing gene dominant (U2AF1 or SRFS2 mutations); C3 was ASXL1 and complex karyotype dominant; C4 was DNA methylation dominant (DNMT3A or TET2 mutations); C5 was NPM1 dominant; C6 was FLT3 mutations dominant; C7 was RUNX1-RUNX1T1 or CBFB-MYH11 fusion dominant; and C8 was abnormal karyotype [-5 or del(5q); -7;-17/abn(17p)] dominant. Thereafter, we linked these genomic clusters with survival outcomes of each treatment arm. Among the 131 patients in the IC group, C5 and C7 were identified as favorable groups while C2 and C8 were classified as adverse groups. On the other hand, in the HMA group, C3 and C5 were allocated to favorable groups and C7 and C8 as adverse. In the HMA/VEN group, C2 and C6 showed favorable survival outcomes while C1 and C7 showed poorer outcomes. Interestingly, we found that an allocation of each genomic cluster to three distinguished (favorable, intermediate, adverse) prognostic groups was changed by the treatment types and survival outcomes of each cluster was substantially different according to different treatment arms. The groups of C1, C5, and C7 which included the HMA/VEN adverse group showed no differences in OS between HMA and HMA/VEN groups, while IC showed better outcomes (HMA vs. HMA/VEN vs. IC, 9.6 vs 9.2 vs 40.5 months, p<0.001). Among the groups of C2, C4, C6, and C8, the patients showed similar median OS between intensive chemotherapy and HMA/VEN, but both treatments showed better outcomes than HMA only (HMA vs HMA/VEN vs IC, 5.5 vs 17.2 vs 17.4 months, p<0.001). In addition, groups C2 and C4 had better median survival by DAC/VEN therapy than other kinds of treatment. (HMA vs HMA/VEN vs IC, 8.2 vs 17.5 vs Not reached, p=0.039). Conclusion: This study suggests that genomic clustering by unsupervised ML could identify genomic groups by co-occurrence patterns having different survival outcomes according to each treatment modality, thus potentially guiding treatment selection in older adults with AML. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

AML-190 Targeted Therapy for R/R FLT3-Positive Acute Myeloid Leukemia is as Effective as Salvage Intensive Chemotherapy but Less Toxic and With Better Long-Term Results

Patients with FLT3-mutated acute myeloid leukemia (AML) have a poor prognosis. The choice of the most optimal therapy is an actual problem. To compare the efficacy, safety, and survival rates of salvage intensive chemotherapy (IC) and targeted therapy in patients with FLT3-mutated relapsed/refractory (R/R) AML. A retrospective study was conducted, which included patients with FLT3-mutated R/R AML. Patients received IC (FLAG±Ida) or gilteritinib (as monotherapy or in combination with venetoclax, azacitidine). All patients received inpatient treatment. The study included 24 patients (12 women, 12 men) with a median age of 42 years (18-83 years); 54.2% (13/24) had relapsed and 45.8% (11/24) had refractory AML. Of the 13 relapsed patients, 8 (61.5%) had early relapse. Thirteen patients received IC and 11 patients received gilteritinib (5 as monotherapy, 2 in combination with venetoclax, 4 in combination with venetoclax and azacitidine). Some patients received salvage IC therapy; others received gilteritinib therapy. Overall response rates (CR, CRMRD-; CRi, MFLS) did not differ significantly between the two groups (63% in the gilteritinib group and 60% in the IC group). The median time to remission was shorter in the IC group than in the gilteritinib group (0.8 vs. 1.5 months, respectively). There was no early mortality in the gilteritinib group; in the IC group, it was 23% (3/11). Serious adverse events were more common in the IC group than in the gilteritinib group (61.5% vs. 18.1%, respectively, P=0.032). In the gilteritinib group, more patients underwent allogeneic bone marrow transplantation (BMT) (77.7% vs. 58.3%). The overall survival and relapse-free survival were longer in the gilteritinib group than in the IC group (20.4 vs. 15.3 months; 7.9 vs. 3.37 months, respectively). Gilteritinib therapy is comparable in efficacy to salvage IC in patients with FLT3-mutated R/R AML but has been shown to be safer and have better survival rates. Gilteritinib is an optimal bridge therapy to allogeneic BMT.

P566: IMPACT OF FRONTLINE INDUCTION APPROACH ON POST-STEM CELL TRANSPLANT (SCT) OUTCOMES IN OLDER ADULTS WITH NEWLY DIAGNOSED ACUTE MYELOID LEUKEMIA (AML)

Background: A hypomethylating agent plus venetoclax (VEN) is standard of care for older, unfit patients (pts) with newly diagnosed AML. However, the optimal induction regimen for older pts with AML who are adequately fit for SCT is not well-established. Aims: We investigated the post-SCT outcomes of older adult pts with newly diagnosed AML based on the intensity of the induction regimen received. Methods: This is a retrospective analysis of pts ≥60 years (yr) of age with newly diagnosed AML who received allogeneic SCT after achieving first remission (CR, CRi or MLFS) between 9/2012 and 7/2021 at our cancer center. Out of 127 pts, 44 pts received intensive chemotherapy (IC) without VEN as induction therapy, 36 pts received low-intensity therapy (LIT) without VEN, and 47 pts received LIT with VEN. Overall survival (OS), relapse-free survival (RFS), cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) after SCT were compared among the groups. Results: The baseline characteristics of the groups are shown in Table 1. Pts in the IC cohort was significantly younger (median age of 63 yrs) than pts who received LIT with or without VEN (median age of 68 yrs, p<0.01). Pts in the IC group were more likely to have ECOG PS of 0 (34%) as compared to those who received LIT (14%, p=0.07). Most pts had adverse ELN cytomolecular risk on presentation (43% in IC, 50% in LIT without VEN, and 55% in LIT with VEN). The median numbers of cycles prior to SCT were 3 in all groups. Pts in LIT without VEN group were more likely to receive matched unrelated donor (75%) than those in the LIT with VEN (49%) and IC groups (50%) and were less likely to receive a haploidentical SCT (3% vs. 17% and 14%, respectively). Pts in LIT with VEN group were more likely to receive reduced-intensity conditioning (92%) prior to SCT, compared with 53% and 58% in the IC and LIT without VEN groups, respectively (p<0.01). HLA matching was well-balanced in 3 groups. The majority of pts were in CR/CRi prior to SCT (100% in the IC group, 95% in the LIT without VEN group, and 92% in the LIT with VEN group), while the rest of pts achieved MLFS. MRD negativity prior to SCT was achieved in more pts treated with IC (77%) or LIT with VEN (66%), compared with LIT without VEN (49%). For the entire cohort, the median follow-up was 37 months (mos) post-SCT. Post-SCT outcomes are shown in Figure 1. The 2-yr OS was highest in the LIT with VEN group (73%) when compared with the IC or LIT without VEN groups (58% and 44%, respectively); OS was statistically superior with LIT with VEN compared with LIT without Ven (p=0.02) and there was a trend towards superior OS compared with IC (p=0.17). 2-yr RFS was also superior in the LIT with VEN group (62%) as compared with the IC or LIT without VEN groups (54% and 42%, respectively). 2-yr CIR was highest in LIT without VEN group (36%), and was similar in the LIT with VEN (19%) and IC groups (18%). 2-yr NRM was highest in IC group (27%) as compared with the LIT with VEN (11%) and LIT without VEN groups (22%) (p=0.02 for IC vs. LIT with VEN). Image:Summary/Conclusion: LIT with VEN resulted in comparable—and possibly superior—outcomes compared with IC in SCT eligible patients ≥60 yrs with newly diagnosed AML. Despite the older age and worse PS of the LIT with VEN group, their post-SCT NRM was lower than those who received IC, which translated to numerically superior OS. These results support LIT with VEN as an effective and tolerable induction strategy in older SCT-eligible pts with newly diagnosed AML.

PB1845: ACUTE MYELOID LEUKEMIA IN THE ELDERLY: A MULTICENTER EXPERIENCE IN COLOMBIA, ON BEHALF OF ACHO’S RENEHOC INVESTIGATORS

Background: The overall survival (OS) of acute myeloid leukemia (AML) decreases as age increases among patients. There are clinical and biological differences in AML in older patients. Even with actual treatments, 70% of patients older than 65 years will die of their disease within 1 year of diagnosis. Aims: Our aim was to characterize the elderly patients (>65 years old) with acute myeloid leukaemia (AML), who were attended in 13 health institutions in Colombia, from 2009 to 2021, including RENEHOC (online platform) and PETHEMA date base (Spanish Program for Hematology Treatments). Methods: An ambispective registry of elderly AML patients, treated in approved centers over the last 12 years. Descriptive statistics were used for patient’s demographic and clinical characteristics. The Kaplan-Meier method was used to assess RFS and OS. Results: A total of 175 patients were included. 54,86% were male and the median age at diagnosis was 73 years old. Most of the patients were classified according to the Eastern Cooperative Oncology Group (ECOG) as ECOG 0-1 (52,7%), ECOG 2 (25 %) and ECOG > 2 (22.3%). 24,26% presented as secondary AML, from these 34% had previous history of myelodysplasic syndrome. At presentation, fever was the main symptom (39,16), followed by bleeding (18,56%). The most frequent comorbidities were hypertension in 20% and diabetes in 9,4%. 24.34% of the patients had one comorbidity while 21.6% of the population had 3 or more. For treatment: 32,9% of the patients received hypomethylating agents, 23,2% received intensive chemotherapy with cytarabine and idarrubicine, 14,1 % had FLUGA (fludarabine low dose and cytarabine) and supportive therapy in 16,7% of the patients. After induction, complete remission (CR) was achieved in 16,9% of patients; CR with incomplete hematologic recovery (Cri) in 7% and 20,9% had primary refractory disease. Mortality during in induction therapy was 12,9%. The median age of patients in the intensive chemotherapy group was 66 years old (66-70), with ECOG 0-2 in 63,8%. The OS was 36.1% (95%CI: 27.0%–45%) at 1 year and 0 % at 5 years of follow-up, the relapse-free survival (RFS) was 38.3 % (95%CI: 27.4%- 49.1%) at 1 year and 0% at 5 years. According to the ECOG. the OS at 1 year was 50,9 % (95%CI: 36.1%–63.9%) for patients with ECOG <2, while the OS at 1 year was 22.7% (95%CI: 12.7%–34.4%) for ECOG >2 with p<0.001. Image:Summary/Conclusion: Management of AML in older patients remains a medical challenge, not only because of the age, but also because older adults are more likely to have impaired functional status and comorbidities that limit treatment options. More refined assessments tools and scales are needed to differentiate between fit and fragile older adults. This multicenter report analyzing real world data from AML patients in Colombia confirmed the impact of clinical factors: age, ECOG on OS and RFS. Challenges includes access to newer treatments with novel, targeted and less intensive therapies. Keywords: acute myeloid leukemia, survival, elderly

A retrospective comparison of salvage intensive chemotherapy versus venetoclax-combined regimen in patients with relapsed/refractory acute myeloid leukemia (AML)

Background:Evidence that a venetoclax (VEN)-combined regimen is effective in relapsed/refractory acute myeloid leukemia (R/R AML) is emerging. However, it is unknown how VEN-combined low intensity treatment compares to intensive chemotherapy (IC) in medically fit patients with R/R AML.Methods:We compared AML patients who received IC (n = 89) to those who received a VEN in combination with hypomethylating agents or low dose cytarabine (VEN combination) (n = 54) as their first- or second-line salvage after failing anthracycline-containing intensive chemotherapy.Results:The median age was 49 years, and significantly more patients in the VEN combination group were in their second salvage and had received prior stem cell transplantation (SCT). Overall response rates including CR, CRi, and MLFS were comparable (44.0% for IC vs. 59.3% for VEN combination, p = 0.081), but VEN combination group compared to IC group tended to show lower treatment related mortality. The rate of bridging to SCT was the same (68.5%), but the percentage of SCT at blast clearance was significantly higher in the VEN-combined group (62.3% vs. 86.5%, p = 0.010). After median follow-up periods of 22.5 (IC) and 11.3 months (VEN combination), the median overall survival was 8.9 (95% CI, 5.4-12.4) and 12.4 months (95% CI, 9.5-15.2) (p = 0.724), respectively.Conclusion:VEN combination provides a comparable anti-leukemic response and survival to salvage IC, and provide a bridge to SCT with better disease control in medically-fit patients with R/R AML.

Long-Term Survival after Intensive Chemotherapy or Hypomethylating Agents in AML Patients Aged 70 Years and Older: A Large Patient Data Set Study from Dataml, SAL and Pethema European Registries

Long-Term Survival after Intensive Chemotherapy or Hypomethylating Agents in AML Patients Aged 70 Years and Older: A Large Patient Data Set Study from Dataml, SAL and Pethema European Registries

Comparison of Salvage Intensive Chemotherapy Versus Venetoclax Combined Regimen in Patients with Relapsed/Refractory Acute Myeloid Leukemia (AML)

▪Introduction: Venetoclax (VEN) combined regimen received FDA approval for newly diagnosed elderly or unfit acute myeloid leukemia (AML) patients. Recently, with increasing use as off-label for relapsed or refractory setting in real practice, the evidence that the regimen is potentially effective in R/R AML is emerging. However, there is no answer to the question how VEN combined treatment compares to intensive chemotherapy (IC) in R/R AML when the patients were intended to be cured with bridging to stem cell transplantation (SCT) after either of these treatments.Methods: Adult AML patients (age ≥18 years) who were refractory to or relapsed after anthracycline plus cytarabine induction were subjected to this analysis. As a group of interest, R/R AML patients who received VEN combined regimen were screened first, and we found a total of 54 corresponding patients between Feb 2020 and Jan 2021. As a comparison, we searched historical controls who were treated with salvage IC during the past two years, revealing a total of 89 patients between Jan 2018 and Jan 2020. Patients analyzed here received VEN-combination or IC as their first or second-line salvage therapy.Results: Overall, the median age was 49 years (range, 18 to 72), and the patients of first line salvage (n=125, 87.4%) were more included. When comparing IC and VEN-combination groups, there were no differences in age, sex, ELN risk groups, cytogenetics, disease type or mutation status. However, more patients in VEN-combination group were in their second line salvage setting (IC vs VEN-combination; 5.6% vs 24.1%, p<0.001) and had received prior SCT (13.5% vs 38.5%, p<0.001). The percentage of patients who had CR, CRi and MLFS were 39.3%, 6.0%, and 0.0% in IC group, and were 40.7%, 11.1%, and 7.4% in VEN group, yielding an overall response rate of 45.2% and 59.3%, respectively (p=0.108). Regarding the bridging to SCT, patients who underwent allo-SCT after salvage therapy were 69.7% in IC and 68.5% in VEN-combination group (p=0.886), of whom 62.9% (IC) and 86.5% (VEN-combination) of patients achieved either CR, CRi or MLFS at SCT (p=0.012). Of note, the median time to SCT were shorter in patients who received VEN-combined regimen (median, 103 days) compared to patients receiving IC (median, 139 days) (p=0.012). The median OS without censoring at the time of SCT were 334 days (95% CI, 198-469) and 381 days (95% CI, 345-416) in IC and VEN-combination group, respectively (p=0.592), after a median follow up period of 685 days and 345 days. VEN-combined regimen was significantly superior to IC in achieving response (p=0.031, OR=2.980 [95% CI 1.105-8.033]) and showed trend towards better survival (p=0.059, HR=0.454 [95% CI 0.200-1.030]) among the patients of fist-line salvage setting only, although significant differences were not shown in overall patients.Conclusion: These findings suggest that VEN-combined treatment is a feasible option for R/R AML and could be chosen over salvage IC in R/R AML based on its anti-leukemic response, bridging to SCT with disease control and survival, which were comparable to IC in overall patients and were tended to be superior in patients of first salvage setting only. DisclosuresKim: AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AIMS Biosciense: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; AML-Hub: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BL & H: Research Funding; BMS & Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Boryung Pharm Co.: Consultancy; Daiichi Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Handok: Consultancy, Honoraria; LG Chem: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria; Pintherapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi Genzyme: Honoraria, Speakers Bureau; SL VaxiGen: Consultancy, Honoraria; VigenCell: Consultancy, Honoraria. Lee: Alexion, AstraZeneca Rare Disease: Honoraria, Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure:venetoclax use in R/R AML: off label use

Outcomes Are Similar Following Allogeneic Hematopoietic Stem Cell Transplant for Newly Diagnosed Patients Who Received Venetoclax + Azacitidine Versus Intensive Chemotherapy

Background: Venetoclax-based therapy regimens are now FDA-approved for treatment of acute myeloid leukemia (AML) in older patients or those unfit to tolerate intensive chemotherapy (IC). Remission rates are high at 60-70% but relapses do frequently occur. Outcomes for newly-diagnosed patients who receive venetoclax-based therapies and proceed to a potentially curative allogeneic stem cell transplant (SCT) have largely been unreported. In the current study we compare outcomes of patients who received SCT following either IC or venetoclax + azacitidine (ven/aza) at the University of Colorado Hospital.Methods: Patients 18 years or older who received SCT in first remission of AML between 2010-2020 were included in the analysis. Patients were stratified into the IC arm if they initially received a backbone of cytarabine and an anthracycline; some patients in this cohort received IC in combination with other targeted agents. Patients who received ven/aza as first-line therapy followed by SCT were grouped in a separate cohort. Demographic and clinical information - including flow cytometry-based (MCF) MRD - was extracted from the electronic medical record.Comparisons of demographic and clinical variables between IC and ven/aza groups were made with t-test, Chi-squared, or Fisher's exact test depending on the nature of the variable. Relapse-free (RFS) and overall (OS) survival were calculated from the day of SCT to the respective endpoint or last documented follow-up using log-rank statistics. Finally, a Cox proportional hazards model was used to assess the interplay between variables pre- and post-SCT. P-values <0.05 were considered significant.Results: We identified 179 patients who received SCT for AML in first remission. Of these patients, 151 received IC and 28 received ven/aza prior to SCT. Patients in the ven/aza group had higher median age than those in the IC group, as well as a higher proportion with adverse ELN genetic risk scoring. Patients in the ven/aza group received less intensive conditioning regimens. Sex, rates of MCF MRD negativity pre-BMT, incidence of severe acute or chronic GVHD, and causes of death were not significantly different between the two groups. There was no difference between the two groups in post-transplant RFS or OS (Figure 1). In a multivariate Cox model of pre-transplant variables predicting OS, the only factor that achieved significance was pre-SCT MCF MRD; the induction regimen was not a multivariate factor. Negative MCF MRD going into SCT was associated with decreased likelihood of relapse, GVHD, and death, respectively.Conclusions: In our cohort of AML patients receiving SCT, we found that ven/aza as a pre-transplant therapy yielded equivalent post-transplant outcomes compared to IC, in a population of older age and with higher ELN genetic risk. MCF MRD pre-SCT was confirmed as a key prognostic factor for post-SCT outcome. These findings support ongoing use of ven/aza as a first line therapy for elderly patients with AML as well as its exploration as a candidate therapy for younger patients. [Display omitted] DisclosuresPollyea: Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other; Aprea: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kiadis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Syndax: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Agios: Other, Research Funding; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Teva: Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Curis, Servier: Other; Pfizer: Research Funding; Syros: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Other: advisory board; Foghorn: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Honoraria, Other: advisory board; Jazz: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: advisory board.

Different Treatment Approaches to Blast Phase-Myeloproliferative Neoplasms

Different Treatment Approaches to Blast Phase-Myeloproliferative Neoplasms

Patients with Acute Myeloid Leukemia on Non-Intensive Therapy: Applicability of the European Leukemia Net Risk Classification

BACKGROUNDThe revised genetic risk classification established by the European Leukemia Net (ELN) in 2017 stratifies patients diagnosed with acute myeloid leukemia (AML) into 3 prognostic categories (favourable, intermediate, and adverse) based on cytogenetic and molecular characteristics.The ELN classification is widely accepted in AML patients despite the fact that validation studies were performed in participants who received exclusively first-line treatment with intensive chemotherapy. For this reason, it is not well established whether the ELN risk groups are applicable to patients on non-intensive first-line treatment.OBJECTIVES- To describe and compare baseline characteristics at diagnosis between patients with AML treated with intensive and non-intensive therapy.- To assess whether the ELN prognostic classification is applicable in these subgroups of patients.METHODSWe retrospectively analysed patients with newly diagnosed AML admitted to our center between 2007 and 2020. Patients with acute promyelocytic leukemia (M3), patients younger than 18 years old and/or patients who received exclusively supportive treatment were excluded. Demographic and clinical data, disease characteristics at diagnosis and first-line treatment were collected. Cytogenetic and molecular characteristics were used to classify patients in ELN risk groups.RESULTSOf the total of patients (n=218), one hundred and fifty-six (71.6%) received intensive chemotherapy treatment, while 62 (28.4%) were treated with non-intensive strategies. Idarubicin and cytarabine based schemes regimens (IA) were administered in most patients (98.6%) who received intensive treatment while the rest received fludarabine based regimens. One patient (0.6%) was treated with danurubicin and cytarabine liposome (CPX-351). Fifty-four (87%) patients treated with non-intensive regimens received hypomethylating agents, mostly azacitidine. Five patients (8%) were treated with venetoclax in combination with a hypomethylating agent.Table 1 shows the characteristics at diagnosis in both groups of patients. Patients who received intensive chemotherapy were younger and had higher leukocyte count, LDH values and a higher percentage of blasts in peripheral blood and bone marrow with a median of 40% and 62% blasts respectively. On the other hand, patients under non-intensive treatment more frequently presented a past history of hemopathy and a higher percentage of bone marrow dysplasia.Regarding ELN stratification significant differences were found between both groups. Patients who received aggressive chemotherapy vs patients who did not, were classified in low (28% vs. 7%), intermediate (36% vs. 58%) and high risk (36% vs. 35%) respectively (Figure 1).At the end of the follow-up, 41% of the patients who had received intensive therapy were alive while only 6.5% of the patients who had received non-intensive treatment were alive. Significant differences in survival were observed between both groups (p<0.01); with 1-year overall survival (OS) of 65.8% for intensive therapy group and 49.6% for non-intensive therapy group.In the intensive chemotherapy group, significant differences in survival were observed according to ELN risk stratification (p<0.01), with 5-year OS of 55%, 29% and 23.9% for low, intermediate and high-risk groups respectively. For low-risk patients, median OS was not reached while it was 20 months for the intermediate risk group and 12.2 months for the high-risk group.However, in patients receiving non-intensive therapies, there were no significant differences in survival among different prognostic categories (p=0.06). In this group, 1-year OS was 25%, 57.6% and 40.7% and median OS was 2.1, 14.8 and 10.1 months for low, intermediate and high-risk groups respectively. See Figure 2.CONCLUSIONS:As validated in previous trials, ELN classification constitutes an adequate prognostic marker for patients with newly diagnosed AML treated with intensive chemotherapy. In our series, this classification does not appear to be a good predictor of survival for patients diagnosed with AML who initiated non-intensive treatments. Further validation in prospective studies are needed to better classify this growing subgroup of patients in clinical practice. [Display omitted] DisclosuresMartín-Rojas: Celgene-BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees. Font Lopez: Pfizer: Membership on an entity's Board of Directors or advisory committees; GILEAD: Membership on an entity's Board of Directors or advisory committees; CELGENE-BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees. Kwon: Novartis, Celgene, Gilead, Pfizer: Consultancy, Honoraria.

AML-225: Outcome with Intensive Chemotherapy vs Hypomethylating Agent-Based Induction Strategies in Patients Older Than 70 Years with Newly Diagnosed, Favorable-Risk Acute Myeloid Leukemia

<h3>Context:</h3> Real-world evidence is lacking regarding the effectiveness of intensive and non-intensive induction strategies in elderly patients with favorable-risk acute myeloid leukemia (AML). <h3>Objectives:</h3> To estimate the rates of complete remission (CR), CR+ CR with incomplete count recovery (CRi), and overall survival (OS) in patients receiving intensive chemotherapy (IC) and hypomethylating agent (HMA)-based induction regimens. <h3>Design:</h3> In this retrospective study, clinical and genomic data were collected by review of records of eligible patients treated at Moffitt Cancer Center. Statistical analyses were performed using SPSS. <h3>Patients:</h3> Elderly (age > 70 years) patients with newly diagnosed, favorable-risk (ELN 2017) AML. <h3>Main Outcomes Measures:</h3> CR, CR+ CRi, OS. <h3>Results:</h3> Out of total 53 patients, 36 (68%) received IC, and 17 (32%) received HMA-based induction regimen. Median age at diagnosis was 74 years (range 70–85). Core binding factor (CBF) abnormalities were detected in 47% patients; 28% had secondary AML. Median blast count was significantly higher in patients receiving IC <i>vs</i> HMA (58% <i>vs</i> 32%, p=0.01). Predominant induction regimen was "7+3" (86%) in the IC group and azacytidine alone (n=11) in HMA cohort. Rate of composite CR (CR+ CRi) was significantly better at 69% (50% CR) in the IC group, compared to 35% (24% CR) with HMA (p=0.01). Six patients on IC and 1 on HMA had early (<30 d) induction-related mortality. Both groups had comparable relapse rates (overall 34%). Median OS was 24.7 months in IC <i>vs</i> 17.5 months in the HMA group, trending toward statistical significance (p=0.058). Overall, 23% patients in the IC group were alive at 5 years, compared to 7% with HMA. In patients with CBF-AML (n=25), median OS was not reached for IC <i>vs</i> 23 months with HMA (p= 0.076); CBF-AML was an independent predictor of survival in the study population. Six patients (3 post-relapse) from the IC group underwent allogeneic stem cell transplant. <h3>Conclusions:</h3> Elderly favorable-risk AML patients had a significantly better composite CR rate on induction treatment with IC than with HMA, with a trend toward improved OS with IC-based induction. A multicenter study with a larger sample size is ongoing to address this question further.

AML-297: Ten-Day Decitabine with Venetoclax vs Intensive Chemotherapy in Relapsed or Refractory Acute Myeloid Leukemia: A Propensity Score-Matched Analysis

Context: Relapsed/refractory (R/R) acute myeloid leukemia (AML) has poor outcomes. While lower-intensity venetoclax-containing regimens are standard for older/unfit patients with newly diagnosed AML, it is unknown how such regimens compare to intensive chemotherapy (IC) for R/R AML. Objective: To compare outcomes of R/R AML treated with 10-day decitabine and venetoclax (DEC10-VEN; NCT03404193) vs IC-based regimens Design: This was a retrospective study. Propensity scores derived from baseline characteristics were used to match patients treated with DEC10-VEN and IC to minimize bias. Patients and Setting: Sixty-five patients in the DEC10-VEN cohort were matched to 130 IC recipients treated at the University of Texas MD Anderson Cancer Center. The median ages for the DEC10-VEN and IC groups were 64 and 58 years, respectively, and baseline characteristics were balanced between the two cohorts. Interventions: DEC10-VEN comprised of decitabine for 10-days and venetoclax 400 mg daily (DiNardo et al. Lancet Haematol. 2020.) IC-based regimens included idarubicin with cytarabine (IA), with or without cladribine (CLIA), clofarabine (CIA), or fludarabine (FIA or FLAG-IDA), with or without additional agents. Main Outcome Measures: Response rates per ELN 2017 criteria, rate of negative MRD by flow cytometry, early mortality, safety, event-free survival (EFS), and overall survival (OS). Results: DEC10-VEN conferred significantly higher responses compared to IC, including higher overall response rate (60% vs 36%, odds ratio [OR]: 3.28, p Conclusions: DEC10-VEN represents an appropriate salvage therapy and may offer better responses and survival compared to IC in adults with R/R AML. Funding: NCI CCSG CA016672, R01CA235622.

Ten-day decitabine with venetoclax versus intensive chemotherapy in relapsed or refractory acute myeloid leukemia: A propensity score-matched analysis.

Relapsed/refractory (R/R) acute myeloid leukemia (AML) has poor outcomes. Although lower-intensity venetoclax-containing regimens are standard for older/unfit patients with newly diagnosed AML, it is unknown how such regimens compare with intensive chemotherapy (IC) for R/R AML. Outcomes of R/R AML treated with 10-day decitabine and venetoclax (DEC10-VEN) were compared with IC-based regimens including idarubicin with cytarabine, with or without cladribine, clofarabine, or fludarabine, with or without additional agents. Propensity scores derived from patient baseline characteristics were used to match DEC10-VEN and IC patients to minimize bias. Sixty-five patients in the DEC10-VEN cohort were matched to 130 IC recipients. The median ages for the DEC10-VEN and IC groups were 64 and 58 years, respectively, and baseline characteristics were balanced between the 2 cohorts. DEC10-VEN conferred significantly higher responses compared with IC including higher overall response rate (60% vs 36%; odds ratio [OR], 3.28; P < .001), complete remission with incomplete hematologic recovery (CRi, 19% vs 6%; OR, 3.56; P = .012), minimal residual disease negativity by flow cytometry (28% vs 13%; OR, 2.48; P = .017), and lower rates of refractory disease. DEC10-VEN led to significantly longer median event-free survival compared with IC (5.7 vs 1.5 months; hazard ratio [HR], 0.46; 95% CI, 0.30-0.70; P < .001), as well as median overall survival (OS; 6.8 vs 4.7 months; HR, 0.56; 95% CI, 0.37-0.86; P = .008). DEC10-VEN was independently associated with improved OS compared with IC in multivariate analysis. Exploratory analysis for OS in 27 subgroups showed that DEC10-VEN was comparable with IC as salvage therapy for R/R AML. DEC10-VEN represents an appropriate salvage therapy and may offer better responses and survival compared with IC in adults with R/R AML.

Hypomethylating Agents Versus Intensive Chemotherapy in Elderly Patients (Age ≥ 70) with Acute Myeloid Leukemia with High White Blood Cell Count

▪BackgroundAcute myeloid leukemia (AML) is primarily a disease of older adults, with 40-50% of patients ≥ 70 years old at diagnosis. Optimal frontline therapy for elderly AML patients remains controversial. Intensive chemotherapy (IC) is often favored in those AML patients who present with leukocytosis (P-AML), yet the evidence to support this practice as opposed to lower intensity therapy is scarce. We aimed to investigate the outcomes of older patients with P-AML based on treatment choice of intensive chemotherapy (IC) vs hypomethylating agents (HMA).MethodsWe retrospectively analyzed 983 elderly AML patients (age ≥ 70 years) treated at Moffitt Cancer Center between 1995 and 2016. Patients with prior exposure to HMA for non-AML diagnoses were excluded. We focused on P-AML patients, defined as baseline WBC ≥ 10x109/L, who received initial therapy with either: intensive chemotherapy (IC) (defined as daunorubicin/cytarabine or equivalent) or hypomethylating agents (HMA) (azacitidine (AZA) or decitabine (DEC)). Age, type of AML, history of antecedent hematologic disease, cytogenetics (per European LeukemiaNet (ELN) criteria), Eastern Cooperative Oncology Group (ECOG) performance status, Charlson comorbidity Index (CCI), complete blood counts and myeloblast percentage at time of diagnosis were obtained for each patient. Kaplan-Meier analysis was performed to calculate overall survival (OS) and the log-rank test was used to determine significance where a p-value of 0.05 was defined as significant. Fisher's exact t-test, hazard ratios (HR) and confidence interval (CI) were calculated using GraphPad Prism v7.03. Univariate and multivariate analysis for the baseline characteristics and type of therapy were performed using SPSS v24.0 to determine prognostic impact.ResultsWithin the entire cohort of older AML patients, we identified 156 who were treated with either HMA (n=41) or IC (n=115). Baseline characteristics of these patients are described in Figure 1A. Significant baseline differences in age, hemoglobin, WBC, ELN cytogenetic category, marrow blast %, and CCI score were observed between the HMA and IC groups. Most notably, the HMA group were older (median age 77 yrs vs 74 yrs, p=0.0037), had a higher incidence of poor-risk cytogenetics (36.6% vs 7%), and were more likely to have CCI score ≥ 3 (29.3% vs 8.7%).Median time of initial treatment was 4.3 months (range: 0.10-70.0 months) in the HMA group compared to 0.5 months (range: 0.33-1.90months) in the IC group. Median OS of the entire group was 7.85 mo. Median OS in the HMA-treated patients was superior to IC treated patients (13.7 mo vs. 5.1 mo, HR 0.63, 95% CI 0.443 - 0.886, p=0.0082) (Figure 1B). The 12 month survival rate was 55.0% in the HMA group and 31.0% in the IC group (p=0.0082). Fifty-two (33%) patients achieved CR/CRi. There was no difference in CR/CRi rates between HMA or IC treated cohorts (30.0% vs. 34.8%, p=0.6983). Rate of relapse upon achievement of CR/CRi was not statistically significant between HMA and IC cohort (41.7% vs. 62.5%, p=0.3181). The 30-day mortality rate was lower in the HMA group compared to the IC group (7.3% vs 24.4%, p=0.0217).Univariate analysis identified treatment type (p<0.0001), cytogenetic risk category (p <0.0001), and ECOG performance status (p<0.0001) as significant prognostic factors for OS. Multivariate analysis identified IC treatment (HR 2.01, 95% CI 1.24-3.26, p=0.005) and poor ECOG performance status (HR 4.30, 95% CI 1.182-15.659, p=0.027) as independent negative predictors of OS.ConclusionsElderly patients (age ≥ 70) with proliferative AML appear to achieve a survival advantage with HMA-based frontline therapy compared to IC, despite a disproportionately higher incidence of traditionally adverse prognostic features (poor-risk cytogenetics, high CCI score) in the HMA group. The reasons for this observation are unclear, but could relate to a higher early death rate with IC or biologic/molecular features that induce greater sensitivity to HMAs, which should be studied in future analyses. Although this study was limited by small size and retrospective nature, our findings cast doubt on the notion that intensive therapy should be the standard frontline approach in elderly patients proliferative/high WBC AML. [Display omitted] DisclosuresSallman:Celgene: Research Funding. Padron:Incyte: Honoraria, Research Funding. Komrokji:Novartis: Honoraria, Speakers Bureau; Celgene: Honoraria. Lancet:Biopath, Biosight, Boehringer Ingelheim, Celator/Jazz, Celgene, Janssen, Karyopharm Therapeutics, and Novartis: Consultancy; Pfizer: Other: Institutional research funding.