AML

Key clinical point: In patients with acute myeloid leukemia (AML), in addition to the induction regimen, only mean platelet volume (MPV) at diagnosis influenced all short- and long-term outcomes. Thus, patients with higher MPV at diagnosis need careful evaluation.

Major finding: In addition to the induction regimen (odds ratio [OR] for hypomethylating agents, 15.879; 95% confidence interval [CI], 4.956-48.881), MPV (OR, 1.694; 95% CI, 1.122-2.556) was the only factor that influenced short- and long-term outcomes including achievement of complete response, overall survival, and progression-free survival.

Study details: This retrospective study included 148 adult patients with AML followed up for a median of 7.4 months.

Disclosures: No source of funding was identified. The authors declared no conflicts of interest.

Source: Tığlıoğlu M et al. Leuk Lymphoma. 2021 May 20. doi: 10.1080/10428194.2021.1929962.

Key clinical point: In patients with acute myeloid leukemia (AML), in addition to the induction regimen, only mean platelet volume (MPV) at diagnosis influenced all short- and long-term outcomes. Thus, patients with higher MPV at diagnosis need careful evaluation.

Major finding: In addition to the induction regimen (odds ratio [OR] for hypomethylating agents, 15.879; 95% confidence interval [CI], 4.956-48.881), MPV (OR, 1.694; 95% CI, 1.122-2.556) was the only factor that influenced short- and long-term outcomes including achievement of complete response, overall survival, and progression-free survival.

Study details: This retrospective study included 148 adult patients with AML followed up for a median of 7.4 months.

Disclosures: No source of funding was identified. The authors declared no conflicts of interest.

Source: Tığlıoğlu M et al. Leuk Lymphoma. 2021 May 20. doi: 10.1080/10428194.2021.1929962.

Key clinical point: In patients with acute myeloid leukemia (AML), in addition to the induction regimen, only mean platelet volume (MPV) at diagnosis influenced all short- and long-term outcomes. Thus, patients with higher MPV at diagnosis need careful evaluation.

Major finding: In addition to the induction regimen (odds ratio [OR] for hypomethylating agents, 15.879; 95% confidence interval [CI], 4.956-48.881), MPV (OR, 1.694; 95% CI, 1.122-2.556) was the only factor that influenced short- and long-term outcomes including achievement of complete response, overall survival, and progression-free survival.

Study details: This retrospective study included 148 adult patients with AML followed up for a median of 7.4 months.

Disclosures: No source of funding was identified. The authors declared no conflicts of interest.

Source: Tığlıoğlu M et al. Leuk Lymphoma. 2021 May 20. doi: 10.1080/10428194.2021.1929962.

Key clinical point: Autologous fecal microbiota transfer (AFMT) was safe and effective for gut microbiota restoration in patients with acute myeloid leukemia (AML) receiving intensive chemotherapy and antibiotics.

Major finding: After AFMT treatment, α-diversity indices returned to their initial median levels (Shannon index, P = .70; Inverse Simpson index, P = .90) and the b-diversity index showed the restoration of microbial communities, particularly for Lachnospiraceae and Ruminococcaceae families. Gut microbiota composition was preserved even after consolidation chemotherapy with high-dose cytarabine. No serious adverse events were reported, and only 3 patients experienced transient gastrointestinal symptoms.

Study details: Findings are from the phase 2 ODYSSEE trial evaluating AFMT treatment in 25 patients with AML treated with intensive chemotherapy and antibiotics.

Disclosures: This study was sponsored by MaaT Pharma. Some investigators including the lead author reported ties with various pharmaceutical companies including MaaT Pharma.

Source: Malard F et al. Nat Commun. 2021 May 25. doi: 10.1038/s41467-021-23376-6.

Key clinical point: Autologous fecal microbiota transfer (AFMT) was safe and effective for gut microbiota restoration in patients with acute myeloid leukemia (AML) receiving intensive chemotherapy and antibiotics.

Major finding: After AFMT treatment, α-diversity indices returned to their initial median levels (Shannon index, P = .70; Inverse Simpson index, P = .90) and the b-diversity index showed the restoration of microbial communities, particularly for Lachnospiraceae and Ruminococcaceae families. Gut microbiota composition was preserved even after consolidation chemotherapy with high-dose cytarabine. No serious adverse events were reported, and only 3 patients experienced transient gastrointestinal symptoms.

Study details: Findings are from the phase 2 ODYSSEE trial evaluating AFMT treatment in 25 patients with AML treated with intensive chemotherapy and antibiotics.

Disclosures: This study was sponsored by MaaT Pharma. Some investigators including the lead author reported ties with various pharmaceutical companies including MaaT Pharma.

Source: Malard F et al. Nat Commun. 2021 May 25. doi: 10.1038/s41467-021-23376-6.

Key clinical point: Autologous fecal microbiota transfer (AFMT) was safe and effective for gut microbiota restoration in patients with acute myeloid leukemia (AML) receiving intensive chemotherapy and antibiotics.

Major finding: After AFMT treatment, α-diversity indices returned to their initial median levels (Shannon index, P = .70; Inverse Simpson index, P = .90) and the b-diversity index showed the restoration of microbial communities, particularly for Lachnospiraceae and Ruminococcaceae families. Gut microbiota composition was preserved even after consolidation chemotherapy with high-dose cytarabine. No serious adverse events were reported, and only 3 patients experienced transient gastrointestinal symptoms.

Study details: Findings are from the phase 2 ODYSSEE trial evaluating AFMT treatment in 25 patients with AML treated with intensive chemotherapy and antibiotics.

Disclosures: This study was sponsored by MaaT Pharma. Some investigators including the lead author reported ties with various pharmaceutical companies including MaaT Pharma.

Source: Malard F et al. Nat Commun. 2021 May 25. doi: 10.1038/s41467-021-23376-6.

Key clinical point: In patients with acute myeloid leukemia (AML), the detection of measurable/minimal residual disease (MRD) via next-generation sequencing (NGS) after the first consolidation (MRD^2nd) might provide better prognostic insight than after the first complete response (CR) postinduction chemotherapy (MRD^1st).

Major finding: Patients with detectable MRD at either time point had a higher cumulative incidence of relapse (CIR), shorter relapse-free survival (RFS), and poorer overall survival (OS; all P less than .001). However, patients with positive MRD^1st but negative MRD^2nd had good prognosis similar to those with negative MRD at both time points (CIR, P = .140; RFS, P = .231; OS, P = .188).

Study details: Findings are from a retrospective study that analyzed 1,005 bone marrow samples serially collected at diagnosis, the first CR after induction chemotherapy, and after the first consolidation chemotherapy from 335 patients with de novo AML.

Disclosures: This study was funded by grants from the Ministry of Science and Technology (Taiwan) and the Ministry of Health and Welfare (Taiwan). Some investigators reported research funding from Celgene. Other authors declared no conflicts of interest.

Source: Tsai CH et al. Blood Adv. 2021 May 17. doi: 10.1182/bloodadvances.2020003738.

Key clinical point: In patients with acute myeloid leukemia (AML), the detection of measurable/minimal residual disease (MRD) via next-generation sequencing (NGS) after the first consolidation (MRD^2nd) might provide better prognostic insight than after the first complete response (CR) postinduction chemotherapy (MRD^1st).

Major finding: Patients with detectable MRD at either time point had a higher cumulative incidence of relapse (CIR), shorter relapse-free survival (RFS), and poorer overall survival (OS; all P less than .001). However, patients with positive MRD^1st but negative MRD^2nd had good prognosis similar to those with negative MRD at both time points (CIR, P = .140; RFS, P = .231; OS, P = .188).

Study details: Findings are from a retrospective study that analyzed 1,005 bone marrow samples serially collected at diagnosis, the first CR after induction chemotherapy, and after the first consolidation chemotherapy from 335 patients with de novo AML.

Disclosures: This study was funded by grants from the Ministry of Science and Technology (Taiwan) and the Ministry of Health and Welfare (Taiwan). Some investigators reported research funding from Celgene. Other authors declared no conflicts of interest.

Source: Tsai CH et al. Blood Adv. 2021 May 17. doi: 10.1182/bloodadvances.2020003738.

Key clinical point: In patients with acute myeloid leukemia (AML), the detection of measurable/minimal residual disease (MRD) via next-generation sequencing (NGS) after the first consolidation (MRD^2nd) might provide better prognostic insight than after the first complete response (CR) postinduction chemotherapy (MRD^1st).

Major finding: Patients with detectable MRD at either time point had a higher cumulative incidence of relapse (CIR), shorter relapse-free survival (RFS), and poorer overall survival (OS; all P less than .001). However, patients with positive MRD^1st but negative MRD^2nd had good prognosis similar to those with negative MRD at both time points (CIR, P = .140; RFS, P = .231; OS, P = .188).

Study details: Findings are from a retrospective study that analyzed 1,005 bone marrow samples serially collected at diagnosis, the first CR after induction chemotherapy, and after the first consolidation chemotherapy from 335 patients with de novo AML.

Disclosures: This study was funded by grants from the Ministry of Science and Technology (Taiwan) and the Ministry of Health and Welfare (Taiwan). Some investigators reported research funding from Celgene. Other authors declared no conflicts of interest.

Source: Tsai CH et al. Blood Adv. 2021 May 17. doi: 10.1182/bloodadvances.2020003738.

Key clinical point: In patients with acute myeloid leukemia (AML) receiving induction chemotherapy, the incidence of breakthrough invasive fungal diseases (IFDs) and consequent use of therapeutic antifungal agents were significantly lower in patients who received posaconazole prophylaxis vs. those who did not.

Major finding: The incidence of proven or probable IFDs and the need for therapeutic antifungal therapies because of IFDs were significantly lower in patients receiving posaconazole prophylaxis vs. those not receiving any prophylaxis (2.5% vs. 9.4%; P = .03). Mold infection, especially invasive aspergillosis, was the most common IFD in both groups.

Study details: Findings are from a retrospective analysis of 247 adult patients with AML who received induction chemotherapy with (n=162) or without (n=85) posaconazole prophylaxis.

Disclosures: This study was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, Republic of Korea. The authors declared no conflicts of interest.

Source: Yang E et al. Medicine (Baltimore). 2021 May 21. doi: 10.1097/MD.0000000000025448.

Key clinical point: In patients with acute myeloid leukemia (AML) receiving induction chemotherapy, the incidence of breakthrough invasive fungal diseases (IFDs) and consequent use of therapeutic antifungal agents were significantly lower in patients who received posaconazole prophylaxis vs. those who did not.

Major finding: The incidence of proven or probable IFDs and the need for therapeutic antifungal therapies because of IFDs were significantly lower in patients receiving posaconazole prophylaxis vs. those not receiving any prophylaxis (2.5% vs. 9.4%; P = .03). Mold infection, especially invasive aspergillosis, was the most common IFD in both groups.

Study details: Findings are from a retrospective analysis of 247 adult patients with AML who received induction chemotherapy with (n=162) or without (n=85) posaconazole prophylaxis.

Disclosures: This study was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, Republic of Korea. The authors declared no conflicts of interest.

Source: Yang E et al. Medicine (Baltimore). 2021 May 21. doi: 10.1097/MD.0000000000025448.

Key clinical point: In patients with acute myeloid leukemia (AML) receiving induction chemotherapy, the incidence of breakthrough invasive fungal diseases (IFDs) and consequent use of therapeutic antifungal agents were significantly lower in patients who received posaconazole prophylaxis vs. those who did not.

Major finding: The incidence of proven or probable IFDs and the need for therapeutic antifungal therapies because of IFDs were significantly lower in patients receiving posaconazole prophylaxis vs. those not receiving any prophylaxis (2.5% vs. 9.4%; P = .03). Mold infection, especially invasive aspergillosis, was the most common IFD in both groups.

Study details: Findings are from a retrospective analysis of 247 adult patients with AML who received induction chemotherapy with (n=162) or without (n=85) posaconazole prophylaxis.

Disclosures: This study was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, Republic of Korea. The authors declared no conflicts of interest.

Source: Yang E et al. Medicine (Baltimore). 2021 May 21. doi: 10.1097/MD.0000000000025448.

Measurable residual disease (MRD) in acute myeloid leukemia (AML) is both predictive and prognostic. However, the best time and method to define its prognostic role remains unclear. This month, 2 papers evaluate the role of MRD testing at different time points during therapy.

The first paper by Tsai et al studied MRD by next-generation sequencing (NGS) after induction and consolidation. The second paper by Kim et al evaluated the role of NGS MRD before and after allogeneic hematopoietic cell transplantation (allo-HCT).

The study by Tsai et al was a retrospective study that analyzed 1005 bone marrow samples serially collected at diagnosis, the first CR after induction chemotherapy (MRD^1st), and after the first consolidation (MRD^2nd) chemotherapy from 335 patients with de novo AML. Patients with antecedent cytopenia, hematologic diseases, and therapy-related AML (t-AML) were excluded. Patients who achieved complete remission with incomplete hematologic recovery (CRi) or had DNMT3A, TET2, and ASXL1 (DTA) only mutations were not included in the analysis. Multiple previous studies have demonstrated that persistence of DTA only mutations have no prognostic impact. Patients with positive MRD^1st (MRD^1st-)but negative MRD^2nd (MRD^2nd-)had good prognosis similar to those with negative MRD at both time points (cumulative incidence of relapse (CIR), P = .140; relapse-free survival (RFS), P = .231; overall survival (OS), P = .188). The median OS for patients with MRD^1st-MRD2^nd- (n = 147), and MRD^1st+MRD^2nd- (n = 60) was not reached compared to 3.1 years for patients with MRD^1st+MRD^2nd+ (n = 75). Only 9 patients progressed from MRD^1st- to MRD^2nd+ and their median survival was 3.6 years.

In the study by Kim et al utilizing NGS pre- and postHCT, the detection of MRD using NGS had a prognostic value before and 1 month after allo-HCT. This study included 146 patients with AML who underwent allo-HCT in complete remission between 2013 and 2018. The OS was 82%, 64%, and 44% for patients who were MRD negative both pre and post HCT, MRD+ then MRD- after alloHCT and MRD+ both pre- and postHCT respectively. In this study, myeloablative conditioning (MAC) pre allo-HCT did not overcome the negative prognostic value of MRD+ disease prior to allo-HCT. This is in contradiction to the BMT CTN0901 where MAC did overcome the negative prognostic impact of MRD+ disease prior to alloHCT. The authors suggest that this difference could be due to the limited number of genes assessed in the BMT CTN0901 study. Both of those studies demonstrate that achieving NGS MRD negativity either with chemotherapy consolidation or alloHCT leads to better outcome and can be used as a meaningful endpoint in AML studies.

Another completely different direction to improve patient outcomes is the evaluation of the gut microbiota. Several studies have demonstrated the negative impact of disturbed gut microbiota on several outcomes in patients with AML receiving intensive chemotherapy. A study by Malard et al demonstrated that autologous fecal microbiota transfer (AFMT) was safe and effective for gut microbiota restoration in patients with AML receiving intensive chemotherapy and antibiotics. After AFMT treatment, α-diversity indices returned to their initial median levels (Shannon index, P = .70; Inverse Simpson index, P = .90) and the b-diversity index showed the restoration of microbial communities, particularly for Lachnospiraceae and Ruminococcaceae families. Gut microbiota composition was preserved even after consolidation chemotherapy with high-dose cytarabine. No serious adverse events were reported, and only 3 patients experienced transient gastrointestinal symptoms. This approach may be considered in the future to improve the outcome of patients or allogeneic stool transfer is another option currently being studied. Clearly gut microbiota have an effect on outcome, and future studies will demonstrate the best and safest way to reconstitute gut microbiota in patients with hematological malignancies.

Measurable residual disease (MRD) in acute myeloid leukemia (AML) is both predictive and prognostic. However, the best time and method to define its prognostic role remains unclear. This month, 2 papers evaluate the role of MRD testing at different time points during therapy.

The first paper by Tsai et al studied MRD by next-generation sequencing (NGS) after induction and consolidation. The second paper by Kim et al evaluated the role of NGS MRD before and after allogeneic hematopoietic cell transplantation (allo-HCT).

The study by Tsai et al was a retrospective study that analyzed 1005 bone marrow samples serially collected at diagnosis, the first CR after induction chemotherapy (MRD^1st), and after the first consolidation (MRD^2nd) chemotherapy from 335 patients with de novo AML. Patients with antecedent cytopenia, hematologic diseases, and therapy-related AML (t-AML) were excluded. Patients who achieved complete remission with incomplete hematologic recovery (CRi) or had DNMT3A, TET2, and ASXL1 (DTA) only mutations were not included in the analysis. Multiple previous studies have demonstrated that persistence of DTA only mutations have no prognostic impact. Patients with positive MRD^1st (MRD^1st-)but negative MRD^2nd (MRD^2nd-)had good prognosis similar to those with negative MRD at both time points (cumulative incidence of relapse (CIR), P = .140; relapse-free survival (RFS), P = .231; overall survival (OS), P = .188). The median OS for patients with MRD^1st-MRD2^nd- (n = 147), and MRD^1st+MRD^2nd- (n = 60) was not reached compared to 3.1 years for patients with MRD^1st+MRD^2nd+ (n = 75). Only 9 patients progressed from MRD^1st- to MRD^2nd+ and their median survival was 3.6 years.

In the study by Kim et al utilizing NGS pre- and postHCT, the detection of MRD using NGS had a prognostic value before and 1 month after allo-HCT. This study included 146 patients with AML who underwent allo-HCT in complete remission between 2013 and 2018. The OS was 82%, 64%, and 44% for patients who were MRD negative both pre and post HCT, MRD+ then MRD- after alloHCT and MRD+ both pre- and postHCT respectively. In this study, myeloablative conditioning (MAC) pre allo-HCT did not overcome the negative prognostic value of MRD+ disease prior to allo-HCT. This is in contradiction to the BMT CTN0901 where MAC did overcome the negative prognostic impact of MRD+ disease prior to alloHCT. The authors suggest that this difference could be due to the limited number of genes assessed in the BMT CTN0901 study. Both of those studies demonstrate that achieving NGS MRD negativity either with chemotherapy consolidation or alloHCT leads to better outcome and can be used as a meaningful endpoint in AML studies.

Another completely different direction to improve patient outcomes is the evaluation of the gut microbiota. Several studies have demonstrated the negative impact of disturbed gut microbiota on several outcomes in patients with AML receiving intensive chemotherapy. A study by Malard et al demonstrated that autologous fecal microbiota transfer (AFMT) was safe and effective for gut microbiota restoration in patients with AML receiving intensive chemotherapy and antibiotics. After AFMT treatment, α-diversity indices returned to their initial median levels (Shannon index, P = .70; Inverse Simpson index, P = .90) and the b-diversity index showed the restoration of microbial communities, particularly for Lachnospiraceae and Ruminococcaceae families. Gut microbiota composition was preserved even after consolidation chemotherapy with high-dose cytarabine. No serious adverse events were reported, and only 3 patients experienced transient gastrointestinal symptoms. This approach may be considered in the future to improve the outcome of patients or allogeneic stool transfer is another option currently being studied. Clearly gut microbiota have an effect on outcome, and future studies will demonstrate the best and safest way to reconstitute gut microbiota in patients with hematological malignancies.

Measurable residual disease (MRD) in acute myeloid leukemia (AML) is both predictive and prognostic. However, the best time and method to define its prognostic role remains unclear. This month, 2 papers evaluate the role of MRD testing at different time points during therapy.

The first paper by Tsai et al studied MRD by next-generation sequencing (NGS) after induction and consolidation. The second paper by Kim et al evaluated the role of NGS MRD before and after allogeneic hematopoietic cell transplantation (allo-HCT).

The study by Tsai et al was a retrospective study that analyzed 1005 bone marrow samples serially collected at diagnosis, the first CR after induction chemotherapy (MRD^1st), and after the first consolidation (MRD^2nd) chemotherapy from 335 patients with de novo AML. Patients with antecedent cytopenia, hematologic diseases, and therapy-related AML (t-AML) were excluded. Patients who achieved complete remission with incomplete hematologic recovery (CRi) or had DNMT3A, TET2, and ASXL1 (DTA) only mutations were not included in the analysis. Multiple previous studies have demonstrated that persistence of DTA only mutations have no prognostic impact. Patients with positive MRD^1st (MRD^1st-)but negative MRD^2nd (MRD^2nd-)had good prognosis similar to those with negative MRD at both time points (cumulative incidence of relapse (CIR), P = .140; relapse-free survival (RFS), P = .231; overall survival (OS), P = .188). The median OS for patients with MRD^1st-MRD2^nd- (n = 147), and MRD^1st+MRD^2nd- (n = 60) was not reached compared to 3.1 years for patients with MRD^1st+MRD^2nd+ (n = 75). Only 9 patients progressed from MRD^1st- to MRD^2nd+ and their median survival was 3.6 years.

In the study by Kim et al utilizing NGS pre- and postHCT, the detection of MRD using NGS had a prognostic value before and 1 month after allo-HCT. This study included 146 patients with AML who underwent allo-HCT in complete remission between 2013 and 2018. The OS was 82%, 64%, and 44% for patients who were MRD negative both pre and post HCT, MRD+ then MRD- after alloHCT and MRD+ both pre- and postHCT respectively. In this study, myeloablative conditioning (MAC) pre allo-HCT did not overcome the negative prognostic value of MRD+ disease prior to allo-HCT. This is in contradiction to the BMT CTN0901 where MAC did overcome the negative prognostic impact of MRD+ disease prior to alloHCT. The authors suggest that this difference could be due to the limited number of genes assessed in the BMT CTN0901 study. Both of those studies demonstrate that achieving NGS MRD negativity either with chemotherapy consolidation or alloHCT leads to better outcome and can be used as a meaningful endpoint in AML studies.

Another completely different direction to improve patient outcomes is the evaluation of the gut microbiota. Several studies have demonstrated the negative impact of disturbed gut microbiota on several outcomes in patients with AML receiving intensive chemotherapy. A study by Malard et al demonstrated that autologous fecal microbiota transfer (AFMT) was safe and effective for gut microbiota restoration in patients with AML receiving intensive chemotherapy and antibiotics. After AFMT treatment, α-diversity indices returned to their initial median levels (Shannon index, P = .70; Inverse Simpson index, P = .90) and the b-diversity index showed the restoration of microbial communities, particularly for Lachnospiraceae and Ruminococcaceae families. Gut microbiota composition was preserved even after consolidation chemotherapy with high-dose cytarabine. No serious adverse events were reported, and only 3 patients experienced transient gastrointestinal symptoms. This approach may be considered in the future to improve the outcome of patients or allogeneic stool transfer is another option currently being studied. Clearly gut microbiota have an effect on outcome, and future studies will demonstrate the best and safest way to reconstitute gut microbiota in patients with hematological malignancies.

Hypomethylating agents are generally considered to be agents of choice for older adults with acute myeloid leukemia who cannot tolerate the rigors of more intensive therapies, but HMAs also can serve as a bridge to transplant for children and young adults with relapsed or refractory acute myeloid leukemia.

That’s according to Himalee S. Sabnis, MD, MSc and colleagues at Emory University and the Aflac Cancer and Blood Disorders Center at Children’s Healthcare of Atlanta.

In a scientific poster presented during the annual meeting of the American Society of Pediatric Hematology/Oncology, the investigators reported results of a retrospective study of HMA use in patients with relapsed or refractory pediatric AML treated in their center.
 

Curative intent and palliation

They identified 25 patients (15 boys) with a median age of 8.3 years (range 1.4 to 21 years) with relapsed/refractory AML who received HMAs for curative intent prior to hematopoietic stem cell transplant (HSCT), palliation, or in combination with donor leukocyte infusion (DLI).

Of the 21 patients with relapsed disease, 16 were in first relapse and 5 were in second relapse or greater. Four of the patients had primary refractory disease. The cytogenetic and molecular features were KMT2A rearrangements in six patients, monosomy 7/deletion 7 q in four patients, 8;21 translocation in three patients, and FLT3-ITD mutations in four patients.

The patients received a median of 5.3 HMA cycles each. Of the 133 total HMA cycles, 87 were with azacitidine, and 46 were with decitabine.

HMAs were used as monotherapy in 62% of cycles, and in combination with other therapies in 38%. Of the combinations, 16 were with donor leukocyte infusion, and 9 were gemtuzumab ozogamicin (Mylotarg).

Of the 13 patients for whom HMAs were used as part of treatment plan with curative intent, 5 proceeded to HSCT, and 8 did not. Of the 5 patients, 1 died from transplant-related causes, and 4 were alive post transplant. Of the 8 patients who did not undergo transplant, 1 had chimeric antigen receptor T- cell (CAR T) therapy, and 7 experienced disease progression.

The mean duration of palliative care was 144 days, with patients receiving from one to nine cycles with an HMA, and no treatment interruptions due to toxicity.

Of 5 patients who received donor leukocyte infusions, 3 reached minimal residual disease negativity; all 3 of these patients had late relapses but remained long-term survivors, the investigators reported.

They concluded that “hypomethylating agents can be used effectively as a bridge to transplantation in relapsed and refractory AML with gemtuzumab ozogamicin being the most common agent for combination therapy. Palliation with HMAs is associated with low toxicity and high tolerability in relapsed/refractory AML. Use of HMAs with DLI can induce sustained remissions in some patients.”

The authors propose prospective clinical trials using HMAs in the relapsed/refractory pediatric AML setting in combination with gemtuzumab ozogamicin, alternative targeted agents, and chemotherapy.

HMAs in treatment-related AML

Shilpa Shahani, MD, a pediatric oncologist and assistant clinical professor of pediatrics at City of Hope in Duarte, Calif., who was not involved in the study, has experience administering HMAs primarily in the adolescent and young adult population with AML.

“Azacitidine and decitabine are good for treatment-related leukemias,” she said in an interview. “They can be used otherwise for people who have relapsed disease and are trying to navigate other options.”

Although they are not standard first-line agents in younger patients, HMAs can play a useful role in therapy for relapsed or refractory disease, she said.

The authors and Dr. Shahani reported having no conflicts of interest to disclose.

Hypomethylating agents are generally considered to be agents of choice for older adults with acute myeloid leukemia who cannot tolerate the rigors of more intensive therapies, but HMAs also can serve as a bridge to transplant for children and young adults with relapsed or refractory acute myeloid leukemia.

That’s according to Himalee S. Sabnis, MD, MSc and colleagues at Emory University and the Aflac Cancer and Blood Disorders Center at Children’s Healthcare of Atlanta.

In a scientific poster presented during the annual meeting of the American Society of Pediatric Hematology/Oncology, the investigators reported results of a retrospective study of HMA use in patients with relapsed or refractory pediatric AML treated in their center.
 

Curative intent and palliation

They identified 25 patients (15 boys) with a median age of 8.3 years (range 1.4 to 21 years) with relapsed/refractory AML who received HMAs for curative intent prior to hematopoietic stem cell transplant (HSCT), palliation, or in combination with donor leukocyte infusion (DLI).

Of the 21 patients with relapsed disease, 16 were in first relapse and 5 were in second relapse or greater. Four of the patients had primary refractory disease. The cytogenetic and molecular features were KMT2A rearrangements in six patients, monosomy 7/deletion 7 q in four patients, 8;21 translocation in three patients, and FLT3-ITD mutations in four patients.

The patients received a median of 5.3 HMA cycles each. Of the 133 total HMA cycles, 87 were with azacitidine, and 46 were with decitabine.

HMAs were used as monotherapy in 62% of cycles, and in combination with other therapies in 38%. Of the combinations, 16 were with donor leukocyte infusion, and 9 were gemtuzumab ozogamicin (Mylotarg).

Of the 13 patients for whom HMAs were used as part of treatment plan with curative intent, 5 proceeded to HSCT, and 8 did not. Of the 5 patients, 1 died from transplant-related causes, and 4 were alive post transplant. Of the 8 patients who did not undergo transplant, 1 had chimeric antigen receptor T- cell (CAR T) therapy, and 7 experienced disease progression.

The mean duration of palliative care was 144 days, with patients receiving from one to nine cycles with an HMA, and no treatment interruptions due to toxicity.

Of 5 patients who received donor leukocyte infusions, 3 reached minimal residual disease negativity; all 3 of these patients had late relapses but remained long-term survivors, the investigators reported.

They concluded that “hypomethylating agents can be used effectively as a bridge to transplantation in relapsed and refractory AML with gemtuzumab ozogamicin being the most common agent for combination therapy. Palliation with HMAs is associated with low toxicity and high tolerability in relapsed/refractory AML. Use of HMAs with DLI can induce sustained remissions in some patients.”

The authors propose prospective clinical trials using HMAs in the relapsed/refractory pediatric AML setting in combination with gemtuzumab ozogamicin, alternative targeted agents, and chemotherapy.

HMAs in treatment-related AML

Shilpa Shahani, MD, a pediatric oncologist and assistant clinical professor of pediatrics at City of Hope in Duarte, Calif., who was not involved in the study, has experience administering HMAs primarily in the adolescent and young adult population with AML.

“Azacitidine and decitabine are good for treatment-related leukemias,” she said in an interview. “They can be used otherwise for people who have relapsed disease and are trying to navigate other options.”

Although they are not standard first-line agents in younger patients, HMAs can play a useful role in therapy for relapsed or refractory disease, she said.

The authors and Dr. Shahani reported having no conflicts of interest to disclose.

Hypomethylating agents are generally considered to be agents of choice for older adults with acute myeloid leukemia who cannot tolerate the rigors of more intensive therapies, but HMAs also can serve as a bridge to transplant for children and young adults with relapsed or refractory acute myeloid leukemia.

That’s according to Himalee S. Sabnis, MD, MSc and colleagues at Emory University and the Aflac Cancer and Blood Disorders Center at Children’s Healthcare of Atlanta.

In a scientific poster presented during the annual meeting of the American Society of Pediatric Hematology/Oncology, the investigators reported results of a retrospective study of HMA use in patients with relapsed or refractory pediatric AML treated in their center.
 

Curative intent and palliation

They identified 25 patients (15 boys) with a median age of 8.3 years (range 1.4 to 21 years) with relapsed/refractory AML who received HMAs for curative intent prior to hematopoietic stem cell transplant (HSCT), palliation, or in combination with donor leukocyte infusion (DLI).

Of the 21 patients with relapsed disease, 16 were in first relapse and 5 were in second relapse or greater. Four of the patients had primary refractory disease. The cytogenetic and molecular features were KMT2A rearrangements in six patients, monosomy 7/deletion 7 q in four patients, 8;21 translocation in three patients, and FLT3-ITD mutations in four patients.

The patients received a median of 5.3 HMA cycles each. Of the 133 total HMA cycles, 87 were with azacitidine, and 46 were with decitabine.

HMAs were used as monotherapy in 62% of cycles, and in combination with other therapies in 38%. Of the combinations, 16 were with donor leukocyte infusion, and 9 were gemtuzumab ozogamicin (Mylotarg).

Of the 13 patients for whom HMAs were used as part of treatment plan with curative intent, 5 proceeded to HSCT, and 8 did not. Of the 5 patients, 1 died from transplant-related causes, and 4 were alive post transplant. Of the 8 patients who did not undergo transplant, 1 had chimeric antigen receptor T- cell (CAR T) therapy, and 7 experienced disease progression.

The mean duration of palliative care was 144 days, with patients receiving from one to nine cycles with an HMA, and no treatment interruptions due to toxicity.

Of 5 patients who received donor leukocyte infusions, 3 reached minimal residual disease negativity; all 3 of these patients had late relapses but remained long-term survivors, the investigators reported.

They concluded that “hypomethylating agents can be used effectively as a bridge to transplantation in relapsed and refractory AML with gemtuzumab ozogamicin being the most common agent for combination therapy. Palliation with HMAs is associated with low toxicity and high tolerability in relapsed/refractory AML. Use of HMAs with DLI can induce sustained remissions in some patients.”

The authors propose prospective clinical trials using HMAs in the relapsed/refractory pediatric AML setting in combination with gemtuzumab ozogamicin, alternative targeted agents, and chemotherapy.

HMAs in treatment-related AML

Shilpa Shahani, MD, a pediatric oncologist and assistant clinical professor of pediatrics at City of Hope in Duarte, Calif., who was not involved in the study, has experience administering HMAs primarily in the adolescent and young adult population with AML.

“Azacitidine and decitabine are good for treatment-related leukemias,” she said in an interview. “They can be used otherwise for people who have relapsed disease and are trying to navigate other options.”

Although they are not standard first-line agents in younger patients, HMAs can play a useful role in therapy for relapsed or refractory disease, she said.

The authors and Dr. Shahani reported having no conflicts of interest to disclose.

Among older patients with acute myeloid leukemia (AML), survival is significantly better when they undergo reduced-intensity conditioning (RIC) before receiving an allogeneic hematopoietic cell transplant (HCT) at first remission. This improvement in survival is seen regardless of key factors such as genotype and the status of minimal residual disease (MRD) after initial chemotherapy, results from two large randomized trials show.

“Two consecutive trials of more than 1,500 older AML patients above 60 years of age demonstrate a consistent benefit for RIC transplant in first remission,” said first author Nigel Russell, MD, of Guy’s Hospital, London, and Nottingham University, England. “This benefit is seen independent of their post-course 1 MRD status,” he added.

Dr. Russell presented the new data at the European Hematology Association (EHA) 2021 Annual Meeting.

Commenting on the study, Charles Craddock, MD, said in an interview that the results “confirm the growing importance of RIC transplantation as a central treatment management strategy in high-risk AML and in this population high risk patients over 60.”

“[These findings] reinforce the evolving treatment paradigm that, in fit adults over 60 with AML, hematopoietic cell transplantation should be considered an essential component of their management plan,” said Dr. Craddock, academic director of the Center for Clinical Haematology, Queen Elizabeth Hospital, Birmingham, England.

Patients with AML who are older than 60 years can achieve complete remission with intensive chemotherapy alone; however, relapse is common, and only about 20% survive for 5 years, Dr. Russell explained.

HCT significantly improves survival outcomes, and the development of RIC has made transplantation accessible to high-risk patients by making the procedure more tolerable with lower toxicity in comparison with conventional conditioning regimens.

However, there is ongoing debate over the prognostic effect of key factors in pretransplant conditioning that may be predictive of the risk for post-transplant relapse – in particular, the presence of MRD after the first course of conditioning, he explained.

To more closely investigate those factors and the rate of survival of older patients with AML who undergo RIC transplant, Dr. Russell and his colleagues evaluated results from the National Cancer Research Institute’s (NCRI) AML16 trial, which was conducted from 2006 to 2012, and interim results from the NCRI AML18 trial, which started in 2015 and is ongoing.

Both trials employed double induction of daunorubicin and clofarabine or, in the AML16 trial, AraC ± gemtuzumab, and in the AML18 trial, daunorubicin and AraC (DA) + gemtuzumab.

In AML18, patients who were MRD positive after course 1 were randomly assigned to undergo either an intensification randomization after either FLAG-Ida or DA+cladribine or DA alone.

In AML16, of 983 patients in first complete response, 144 (15%) subsequently underwent RIC transplant. The median follow-up for survival from complete response was 45 months.

In the AML18 trial, of 847 patients, 648 patients achieved complete response. Among them, 201 (31%) underwent transplant. The median follow-up of survival was 45 months.

The results of both trials showed greater benefit with RIC transplant versus chemotherapy alone.

In the AML16 trial, among patients aged 60 to 70 who received RIC, survival at 5 years was significantly improved compared with chemotherapy alone (37% vs. 19%; hazard ratio, 0.65; 95% confidence interval, 0.52-0.82; P < .001).

In AML16, the higher survival benefit in comparison with chemotherapy alone was observed in the RIC group across subgroups of risk level, as stratified according to in the multivariate Wheatley risk group score. Subgroup stratification was based on age, cytogenics, and other factors (HR, 0.66; 95% CI, 0.53-0.83; P < .001).

Importantly, the survival benefits were significantly greater with RIC transplant regardless of MRD-negative or MRD-positive status after course 1 (HR, 0.68; 95% CI, 0.54-0.85; P < .001).

Allograft transplant was also more favorable regardless of FLT3 ITD or NPM1 mutation status (P for heterogeneity by genetic subgroups, 0.61).

In AML16, no groups were found to have benefited more with RIC. Consequently, the criteria for transplant in AML18 trial were based on patients’ health status and donor availability.

An interim analysis of the ongoing AML 18 trial further underscored an overall benefit of RIC transplant. Rates of 3-year survival from remission were 48% with RIC transplant, versus 37.4% with chemotherapy alone (P = .027). The benefit was independent of MRD status after conditioning course 1, similar to the AML16 results (HR, 0.71; 95% CI, 0.54-0.95; P = .02).

Although the rate of transplantation in the AML18 trial was higher among patients who were MRD positive in comparison with those who were MRD negative (36% vs. 24.8%), the rates of post-transplant survival were not significantly different between those who were MRD positive and those who were MRD negative after course 1 (51.1% vs. 46.6% at 3 years; P = .84).

The authors evaluated the effects of a second conditioning course on transplant outcomes among patients who did not initially achieve an MRD-negative complete remission.

They found that 60% of patients did convert from MRD-positive to MRD-negative status after course 2. Among those patients, the survival versus chemotherapy alone was substantially higher (HR, 0.32; 95% CI, 0.11-0.92) compared to those who remained MRD-negative (HR 0.74; 95% CI, 0.32-1.72).

However, the authors note that, owing to a lack of heterogeneity, the results don’t necessarily mean that the patients who remained MRD positive did not also benefit from transplant.

“There was a significant benefit for transplant in those who converted to MRD negativity,” Dr. Russell said.

“With a hazard ratio of .32, this was far superior to those who remained MRD-positive post course 2,” he said.

“These results show that MRD status after course 1 is important information in terms of response to therapy and can alter your treatment strategy if you’re considering a transplant as an option for these patients,” Dr. Russell told this news organization.

In further commenting, Dr. Craddock said the research highlights the importance of randomized trials with regard to whether patients who are MRD-positive before transplant will benefit from an additional course of therapy to reduce the MRD load.

“Most get two courses, but the question is, if they are still MRD positive, should they get a third course, and if so, what should that look like?” he said.

“There are currently no randomized controlled trials to address that ongoing question, and they need to be done,” he added.

Dr. Russell has relationships with Pfizer, Astellas, and Jazz Pharma. Dr. Craddock has a relationship with Bristol-Myers Squibb.

A version of this article first appeared on Medscape.com.

Among older patients with acute myeloid leukemia (AML), survival is significantly better when they undergo reduced-intensity conditioning (RIC) before receiving an allogeneic hematopoietic cell transplant (HCT) at first remission. This improvement in survival is seen regardless of key factors such as genotype and the status of minimal residual disease (MRD) after initial chemotherapy, results from two large randomized trials show.

“Two consecutive trials of more than 1,500 older AML patients above 60 years of age demonstrate a consistent benefit for RIC transplant in first remission,” said first author Nigel Russell, MD, of Guy’s Hospital, London, and Nottingham University, England. “This benefit is seen independent of their post-course 1 MRD status,” he added.

Dr. Russell presented the new data at the European Hematology Association (EHA) 2021 Annual Meeting.

Commenting on the study, Charles Craddock, MD, said in an interview that the results “confirm the growing importance of RIC transplantation as a central treatment management strategy in high-risk AML and in this population high risk patients over 60.”

“[These findings] reinforce the evolving treatment paradigm that, in fit adults over 60 with AML, hematopoietic cell transplantation should be considered an essential component of their management plan,” said Dr. Craddock, academic director of the Center for Clinical Haematology, Queen Elizabeth Hospital, Birmingham, England.

Patients with AML who are older than 60 years can achieve complete remission with intensive chemotherapy alone; however, relapse is common, and only about 20% survive for 5 years, Dr. Russell explained.

HCT significantly improves survival outcomes, and the development of RIC has made transplantation accessible to high-risk patients by making the procedure more tolerable with lower toxicity in comparison with conventional conditioning regimens.

However, there is ongoing debate over the prognostic effect of key factors in pretransplant conditioning that may be predictive of the risk for post-transplant relapse – in particular, the presence of MRD after the first course of conditioning, he explained.

To more closely investigate those factors and the rate of survival of older patients with AML who undergo RIC transplant, Dr. Russell and his colleagues evaluated results from the National Cancer Research Institute’s (NCRI) AML16 trial, which was conducted from 2006 to 2012, and interim results from the NCRI AML18 trial, which started in 2015 and is ongoing.

Both trials employed double induction of daunorubicin and clofarabine or, in the AML16 trial, AraC ± gemtuzumab, and in the AML18 trial, daunorubicin and AraC (DA) + gemtuzumab.

In AML18, patients who were MRD positive after course 1 were randomly assigned to undergo either an intensification randomization after either FLAG-Ida or DA+cladribine or DA alone.

In AML16, of 983 patients in first complete response, 144 (15%) subsequently underwent RIC transplant. The median follow-up for survival from complete response was 45 months.

In the AML18 trial, of 847 patients, 648 patients achieved complete response. Among them, 201 (31%) underwent transplant. The median follow-up of survival was 45 months.

The results of both trials showed greater benefit with RIC transplant versus chemotherapy alone.

In the AML16 trial, among patients aged 60 to 70 who received RIC, survival at 5 years was significantly improved compared with chemotherapy alone (37% vs. 19%; hazard ratio, 0.65; 95% confidence interval, 0.52-0.82; P < .001).

In AML16, the higher survival benefit in comparison with chemotherapy alone was observed in the RIC group across subgroups of risk level, as stratified according to in the multivariate Wheatley risk group score. Subgroup stratification was based on age, cytogenics, and other factors (HR, 0.66; 95% CI, 0.53-0.83; P < .001).

Importantly, the survival benefits were significantly greater with RIC transplant regardless of MRD-negative or MRD-positive status after course 1 (HR, 0.68; 95% CI, 0.54-0.85; P < .001).

Allograft transplant was also more favorable regardless of FLT3 ITD or NPM1 mutation status (P for heterogeneity by genetic subgroups, 0.61).

In AML16, no groups were found to have benefited more with RIC. Consequently, the criteria for transplant in AML18 trial were based on patients’ health status and donor availability.

An interim analysis of the ongoing AML 18 trial further underscored an overall benefit of RIC transplant. Rates of 3-year survival from remission were 48% with RIC transplant, versus 37.4% with chemotherapy alone (P = .027). The benefit was independent of MRD status after conditioning course 1, similar to the AML16 results (HR, 0.71; 95% CI, 0.54-0.95; P = .02).

Although the rate of transplantation in the AML18 trial was higher among patients who were MRD positive in comparison with those who were MRD negative (36% vs. 24.8%), the rates of post-transplant survival were not significantly different between those who were MRD positive and those who were MRD negative after course 1 (51.1% vs. 46.6% at 3 years; P = .84).

The authors evaluated the effects of a second conditioning course on transplant outcomes among patients who did not initially achieve an MRD-negative complete remission.

They found that 60% of patients did convert from MRD-positive to MRD-negative status after course 2. Among those patients, the survival versus chemotherapy alone was substantially higher (HR, 0.32; 95% CI, 0.11-0.92) compared to those who remained MRD-negative (HR 0.74; 95% CI, 0.32-1.72).

However, the authors note that, owing to a lack of heterogeneity, the results don’t necessarily mean that the patients who remained MRD positive did not also benefit from transplant.

“There was a significant benefit for transplant in those who converted to MRD negativity,” Dr. Russell said.

“With a hazard ratio of .32, this was far superior to those who remained MRD-positive post course 2,” he said.

“These results show that MRD status after course 1 is important information in terms of response to therapy and can alter your treatment strategy if you’re considering a transplant as an option for these patients,” Dr. Russell told this news organization.

In further commenting, Dr. Craddock said the research highlights the importance of randomized trials with regard to whether patients who are MRD-positive before transplant will benefit from an additional course of therapy to reduce the MRD load.

“Most get two courses, but the question is, if they are still MRD positive, should they get a third course, and if so, what should that look like?” he said.

“There are currently no randomized controlled trials to address that ongoing question, and they need to be done,” he added.

Dr. Russell has relationships with Pfizer, Astellas, and Jazz Pharma. Dr. Craddock has a relationship with Bristol-Myers Squibb.

A version of this article first appeared on Medscape.com.

Among older patients with acute myeloid leukemia (AML), survival is significantly better when they undergo reduced-intensity conditioning (RIC) before receiving an allogeneic hematopoietic cell transplant (HCT) at first remission. This improvement in survival is seen regardless of key factors such as genotype and the status of minimal residual disease (MRD) after initial chemotherapy, results from two large randomized trials show.

“Two consecutive trials of more than 1,500 older AML patients above 60 years of age demonstrate a consistent benefit for RIC transplant in first remission,” said first author Nigel Russell, MD, of Guy’s Hospital, London, and Nottingham University, England. “This benefit is seen independent of their post-course 1 MRD status,” he added.

Dr. Russell presented the new data at the European Hematology Association (EHA) 2021 Annual Meeting.

Commenting on the study, Charles Craddock, MD, said in an interview that the results “confirm the growing importance of RIC transplantation as a central treatment management strategy in high-risk AML and in this population high risk patients over 60.”

“[These findings] reinforce the evolving treatment paradigm that, in fit adults over 60 with AML, hematopoietic cell transplantation should be considered an essential component of their management plan,” said Dr. Craddock, academic director of the Center for Clinical Haematology, Queen Elizabeth Hospital, Birmingham, England.

Patients with AML who are older than 60 years can achieve complete remission with intensive chemotherapy alone; however, relapse is common, and only about 20% survive for 5 years, Dr. Russell explained.

HCT significantly improves survival outcomes, and the development of RIC has made transplantation accessible to high-risk patients by making the procedure more tolerable with lower toxicity in comparison with conventional conditioning regimens.

However, there is ongoing debate over the prognostic effect of key factors in pretransplant conditioning that may be predictive of the risk for post-transplant relapse – in particular, the presence of MRD after the first course of conditioning, he explained.

To more closely investigate those factors and the rate of survival of older patients with AML who undergo RIC transplant, Dr. Russell and his colleagues evaluated results from the National Cancer Research Institute’s (NCRI) AML16 trial, which was conducted from 2006 to 2012, and interim results from the NCRI AML18 trial, which started in 2015 and is ongoing.

Both trials employed double induction of daunorubicin and clofarabine or, in the AML16 trial, AraC ± gemtuzumab, and in the AML18 trial, daunorubicin and AraC (DA) + gemtuzumab.

In AML18, patients who were MRD positive after course 1 were randomly assigned to undergo either an intensification randomization after either FLAG-Ida or DA+cladribine or DA alone.

In AML16, of 983 patients in first complete response, 144 (15%) subsequently underwent RIC transplant. The median follow-up for survival from complete response was 45 months.

In the AML18 trial, of 847 patients, 648 patients achieved complete response. Among them, 201 (31%) underwent transplant. The median follow-up of survival was 45 months.

The results of both trials showed greater benefit with RIC transplant versus chemotherapy alone.

In the AML16 trial, among patients aged 60 to 70 who received RIC, survival at 5 years was significantly improved compared with chemotherapy alone (37% vs. 19%; hazard ratio, 0.65; 95% confidence interval, 0.52-0.82; P < .001).

In AML16, the higher survival benefit in comparison with chemotherapy alone was observed in the RIC group across subgroups of risk level, as stratified according to in the multivariate Wheatley risk group score. Subgroup stratification was based on age, cytogenics, and other factors (HR, 0.66; 95% CI, 0.53-0.83; P < .001).

Importantly, the survival benefits were significantly greater with RIC transplant regardless of MRD-negative or MRD-positive status after course 1 (HR, 0.68; 95% CI, 0.54-0.85; P < .001).

Allograft transplant was also more favorable regardless of FLT3 ITD or NPM1 mutation status (P for heterogeneity by genetic subgroups, 0.61).

In AML16, no groups were found to have benefited more with RIC. Consequently, the criteria for transplant in AML18 trial were based on patients’ health status and donor availability.

An interim analysis of the ongoing AML 18 trial further underscored an overall benefit of RIC transplant. Rates of 3-year survival from remission were 48% with RIC transplant, versus 37.4% with chemotherapy alone (P = .027). The benefit was independent of MRD status after conditioning course 1, similar to the AML16 results (HR, 0.71; 95% CI, 0.54-0.95; P = .02).

Although the rate of transplantation in the AML18 trial was higher among patients who were MRD positive in comparison with those who were MRD negative (36% vs. 24.8%), the rates of post-transplant survival were not significantly different between those who were MRD positive and those who were MRD negative after course 1 (51.1% vs. 46.6% at 3 years; P = .84).

The authors evaluated the effects of a second conditioning course on transplant outcomes among patients who did not initially achieve an MRD-negative complete remission.

They found that 60% of patients did convert from MRD-positive to MRD-negative status after course 2. Among those patients, the survival versus chemotherapy alone was substantially higher (HR, 0.32; 95% CI, 0.11-0.92) compared to those who remained MRD-negative (HR 0.74; 95% CI, 0.32-1.72).

However, the authors note that, owing to a lack of heterogeneity, the results don’t necessarily mean that the patients who remained MRD positive did not also benefit from transplant.

“There was a significant benefit for transplant in those who converted to MRD negativity,” Dr. Russell said.

“With a hazard ratio of .32, this was far superior to those who remained MRD-positive post course 2,” he said.

“These results show that MRD status after course 1 is important information in terms of response to therapy and can alter your treatment strategy if you’re considering a transplant as an option for these patients,” Dr. Russell told this news organization.

In further commenting, Dr. Craddock said the research highlights the importance of randomized trials with regard to whether patients who are MRD-positive before transplant will benefit from an additional course of therapy to reduce the MRD load.

“Most get two courses, but the question is, if they are still MRD positive, should they get a third course, and if so, what should that look like?” he said.

“There are currently no randomized controlled trials to address that ongoing question, and they need to be done,” he added.

Dr. Russell has relationships with Pfizer, Astellas, and Jazz Pharma. Dr. Craddock has a relationship with Bristol-Myers Squibb.

A version of this article first appeared on Medscape.com.

Key clinical point: Venetoclax-based therapies offered good efficacy with an acceptable toxicity profile in a real-life setting of patients with relapsed/refractory acute myeloid leukemia (AML).

Major finding: During median follow-up of 10.7 months, composite complete remission was achieved in 55% of patients, of which 61% achieved minimal residual disease negativity. Overall survival and event-free survival were 10.7 and 4.5 months, respectively. Grade 4 neutropenia, thrombocytopenia, and febrile neutropenia occurred in 100%, 95%, and 45% of patients, respectively.

Study details: Data come from retrospective assessment of 47 patients with relapsed/refractory AML treated with venetoclax in combination with azacytidine, decitabine, or low-dose cytarabine.

Disclosures: This study was supported by a grant from AIRC to the MYNERVA project. The authors declared no conflicts of interest.

Source: Piccini M et al. J Clin Med. 2021 Apr 14. doi: 10.3390/jcm10081684.

Key clinical point: Venetoclax-based therapies offered good efficacy with an acceptable toxicity profile in a real-life setting of patients with relapsed/refractory acute myeloid leukemia (AML).

Major finding: During median follow-up of 10.7 months, composite complete remission was achieved in 55% of patients, of which 61% achieved minimal residual disease negativity. Overall survival and event-free survival were 10.7 and 4.5 months, respectively. Grade 4 neutropenia, thrombocytopenia, and febrile neutropenia occurred in 100%, 95%, and 45% of patients, respectively.

Study details: Data come from retrospective assessment of 47 patients with relapsed/refractory AML treated with venetoclax in combination with azacytidine, decitabine, or low-dose cytarabine.

Disclosures: This study was supported by a grant from AIRC to the MYNERVA project. The authors declared no conflicts of interest.

Source: Piccini M et al. J Clin Med. 2021 Apr 14. doi: 10.3390/jcm10081684.

Key clinical point: Venetoclax-based therapies offered good efficacy with an acceptable toxicity profile in a real-life setting of patients with relapsed/refractory acute myeloid leukemia (AML).

Major finding: During median follow-up of 10.7 months, composite complete remission was achieved in 55% of patients, of which 61% achieved minimal residual disease negativity. Overall survival and event-free survival were 10.7 and 4.5 months, respectively. Grade 4 neutropenia, thrombocytopenia, and febrile neutropenia occurred in 100%, 95%, and 45% of patients, respectively.

Study details: Data come from retrospective assessment of 47 patients with relapsed/refractory AML treated with venetoclax in combination with azacytidine, decitabine, or low-dose cytarabine.

Disclosures: This study was supported by a grant from AIRC to the MYNERVA project. The authors declared no conflicts of interest.

Source: Piccini M et al. J Clin Med. 2021 Apr 14. doi: 10.3390/jcm10081684.

Key clinical point: Age has a significant impact on the biology and outcomes of patients with acute myeloid leukemia (AML). The proportion of patients in the favorable-risk group receiving induction remission chemotherapy and rates of complete response (CR) among patients who received induction therapy decreased with age.

Major finding: Only 6% of patients older than 70 years were in the favorable-risk group, and less than 50% of patients older than 70 years received induction therapy. After induction therapy, 81.5% of patients with acute promyelocytic leukemia (APL) and 62.4% of non-APL patients achieved CR, which decreased with increasing age.

Study details: Findings are from a retrospective analysis of 3,011 adult patients with AML, of which 329 patients had APL and 2,682 were non-APL patients.

Disclosures: This study was supported by the Korean Society of Hematology AML/MDS Working Party and funding from Gachon University to H Kim. The authors declared no conflicts of interest.

Source: Yoo KH et al. PLoS One. 2021 May 7. doi: 10.1371/journal.pone.0251011.

Key clinical point: Age has a significant impact on the biology and outcomes of patients with acute myeloid leukemia (AML). The proportion of patients in the favorable-risk group receiving induction remission chemotherapy and rates of complete response (CR) among patients who received induction therapy decreased with age.

Major finding: Only 6% of patients older than 70 years were in the favorable-risk group, and less than 50% of patients older than 70 years received induction therapy. After induction therapy, 81.5% of patients with acute promyelocytic leukemia (APL) and 62.4% of non-APL patients achieved CR, which decreased with increasing age.

Study details: Findings are from a retrospective analysis of 3,011 adult patients with AML, of which 329 patients had APL and 2,682 were non-APL patients.

Disclosures: This study was supported by the Korean Society of Hematology AML/MDS Working Party and funding from Gachon University to H Kim. The authors declared no conflicts of interest.

Source: Yoo KH et al. PLoS One. 2021 May 7. doi: 10.1371/journal.pone.0251011.

Key clinical point: Age has a significant impact on the biology and outcomes of patients with acute myeloid leukemia (AML). The proportion of patients in the favorable-risk group receiving induction remission chemotherapy and rates of complete response (CR) among patients who received induction therapy decreased with age.

Major finding: Only 6% of patients older than 70 years were in the favorable-risk group, and less than 50% of patients older than 70 years received induction therapy. After induction therapy, 81.5% of patients with acute promyelocytic leukemia (APL) and 62.4% of non-APL patients achieved CR, which decreased with increasing age.

Study details: Findings are from a retrospective analysis of 3,011 adult patients with AML, of which 329 patients had APL and 2,682 were non-APL patients.

Disclosures: This study was supported by the Korean Society of Hematology AML/MDS Working Party and funding from Gachon University to H Kim. The authors declared no conflicts of interest.

Source: Yoo KH et al. PLoS One. 2021 May 7. doi: 10.1371/journal.pone.0251011.

Key clinical point: Treatment with FMS-like tyrosine kinase inhibitor (FLT3i)-based induction and allogeneic stem cell transplantation (allo-SCT) in the first complete remission (CR1) improved survival in patients with newly diagnosed acute myeloid leukemia (AML) with very low FLT3 allelic burden (0.1 or lower).

Major finding: The 5-year overall survival (OS) rates among patients who received FLT3i induction and allo-SCT in CR1 vs. those who neither received FLT3i nor allo-SCT in CR1 were 100% vs. 27% (P = .02). The 5-year OS rate among patients who did not receive FLT3i-based induction but underwent allo-SCT in CR1 was 71%. Moreover, patients who received FLT3i-based induction and underwent allo-SCT achieved the highest OS.

Study details: Findings are from the retrospective analysis of 50 patients with newly diagnosed FLT3-mutated AML. Patients received frontline chemotherapy without FLT3i (n=30) or induction therapy with FLT3i (n=20).

Disclosures: This study was partly supported by the MD Anderson Cancer Centre Support Grant. Some investigators including the lead author reported research funding, personal fees, grants, honoraria, consultancy, and advisory roles for various pharmaceutical companies.

Source: Yilmaz M et al. Am J Hematol. 2021 Apr 23. doi: 10.1002/ajh.26202.

Key clinical point: Treatment with FMS-like tyrosine kinase inhibitor (FLT3i)-based induction and allogeneic stem cell transplantation (allo-SCT) in the first complete remission (CR1) improved survival in patients with newly diagnosed acute myeloid leukemia (AML) with very low FLT3 allelic burden (0.1 or lower).

Major finding: The 5-year overall survival (OS) rates among patients who received FLT3i induction and allo-SCT in CR1 vs. those who neither received FLT3i nor allo-SCT in CR1 were 100% vs. 27% (P = .02). The 5-year OS rate among patients who did not receive FLT3i-based induction but underwent allo-SCT in CR1 was 71%. Moreover, patients who received FLT3i-based induction and underwent allo-SCT achieved the highest OS.

Study details: Findings are from the retrospective analysis of 50 patients with newly diagnosed FLT3-mutated AML. Patients received frontline chemotherapy without FLT3i (n=30) or induction therapy with FLT3i (n=20).

Disclosures: This study was partly supported by the MD Anderson Cancer Centre Support Grant. Some investigators including the lead author reported research funding, personal fees, grants, honoraria, consultancy, and advisory roles for various pharmaceutical companies.

Source: Yilmaz M et al. Am J Hematol. 2021 Apr 23. doi: 10.1002/ajh.26202.

Key clinical point: Treatment with FMS-like tyrosine kinase inhibitor (FLT3i)-based induction and allogeneic stem cell transplantation (allo-SCT) in the first complete remission (CR1) improved survival in patients with newly diagnosed acute myeloid leukemia (AML) with very low FLT3 allelic burden (0.1 or lower).

Major finding: The 5-year overall survival (OS) rates among patients who received FLT3i induction and allo-SCT in CR1 vs. those who neither received FLT3i nor allo-SCT in CR1 were 100% vs. 27% (P = .02). The 5-year OS rate among patients who did not receive FLT3i-based induction but underwent allo-SCT in CR1 was 71%. Moreover, patients who received FLT3i-based induction and underwent allo-SCT achieved the highest OS.

Study details: Findings are from the retrospective analysis of 50 patients with newly diagnosed FLT3-mutated AML. Patients received frontline chemotherapy without FLT3i (n=30) or induction therapy with FLT3i (n=20).

Disclosures: This study was partly supported by the MD Anderson Cancer Centre Support Grant. Some investigators including the lead author reported research funding, personal fees, grants, honoraria, consultancy, and advisory roles for various pharmaceutical companies.

Source: Yilmaz M et al. Am J Hematol. 2021 Apr 23. doi: 10.1002/ajh.26202.