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.

Key clinical point: Tyrosine kinase inhibitor (TKI) discontinuation was feasible and safe not only at the first but also at the second attempt in patients with chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: At the first attempt of TKI discontinuation, 28 patients achieved sustained treatment-free remission (TFR, 53.4%; 95% confidence interval [CI], 39.0%-65.9%) at 1 year. Among the 10 patients who attempted the second TKI discontinuation, 4 achieved the second TFR at 1 year (TFR, 37.5%; 95% CI, 9.9%-65.9%). Other 6 patients with the second relapse achieved at least a major molecular response within 6 months after resuming TKI treatment.

Study details: Findings are from a retrospective analysis of 53 patients with Philadelphia chromosome-positive CML-CP who attempted TKI discontinuation following a durable deep molecular response on TKI therapy.

Disclosures: This work was supported by the Shinnihon Foundation of Advanced Medical Treatment Research, Okinaka Memorial Institute for Medical Research, and the Japan Society for the Promotion of Science. S Kimura reported ties with various pharmaceutical companies. Other authors declared no conflicts of interest.

Source: Ureshino H et al. Hematol Oncol. 2021 Jun 11. doi: 10.1002/hon.2896.

Key clinical point: Tyrosine kinase inhibitor (TKI) discontinuation was feasible and safe not only at the first but also at the second attempt in patients with chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: At the first attempt of TKI discontinuation, 28 patients achieved sustained treatment-free remission (TFR, 53.4%; 95% confidence interval [CI], 39.0%-65.9%) at 1 year. Among the 10 patients who attempted the second TKI discontinuation, 4 achieved the second TFR at 1 year (TFR, 37.5%; 95% CI, 9.9%-65.9%). Other 6 patients with the second relapse achieved at least a major molecular response within 6 months after resuming TKI treatment.

Study details: Findings are from a retrospective analysis of 53 patients with Philadelphia chromosome-positive CML-CP who attempted TKI discontinuation following a durable deep molecular response on TKI therapy.

Disclosures: This work was supported by the Shinnihon Foundation of Advanced Medical Treatment Research, Okinaka Memorial Institute for Medical Research, and the Japan Society for the Promotion of Science. S Kimura reported ties with various pharmaceutical companies. Other authors declared no conflicts of interest.

Source: Ureshino H et al. Hematol Oncol. 2021 Jun 11. doi: 10.1002/hon.2896.

Key clinical point: Tyrosine kinase inhibitor (TKI) discontinuation was feasible and safe not only at the first but also at the second attempt in patients with chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: At the first attempt of TKI discontinuation, 28 patients achieved sustained treatment-free remission (TFR, 53.4%; 95% confidence interval [CI], 39.0%-65.9%) at 1 year. Among the 10 patients who attempted the second TKI discontinuation, 4 achieved the second TFR at 1 year (TFR, 37.5%; 95% CI, 9.9%-65.9%). Other 6 patients with the second relapse achieved at least a major molecular response within 6 months after resuming TKI treatment.

Study details: Findings are from a retrospective analysis of 53 patients with Philadelphia chromosome-positive CML-CP who attempted TKI discontinuation following a durable deep molecular response on TKI therapy.

Disclosures: This work was supported by the Shinnihon Foundation of Advanced Medical Treatment Research, Okinaka Memorial Institute for Medical Research, and the Japan Society for the Promotion of Science. S Kimura reported ties with various pharmaceutical companies. Other authors declared no conflicts of interest.

Source: Ureshino H et al. Hematol Oncol. 2021 Jun 11. doi: 10.1002/hon.2896.

Key clinical point: Among patients with chronic myeloid leukemia (CML), the mean daily dose of nilotinib, either as the first- or second-line treatment prescribed in Italian clinical practice settings, was lower than the approved dose reported in the summary of product characteristics as the first- (600 mg daily) and second-line (800 mg daily) treatment.

Major finding: Based on the last determination of the BCR/ABL test, the mean daily nilotinib dose was 498.54 mg (mean treatment duration, 811 days) and 565.2 mg (mean treatment duration, 323.1 days) for patients treated with first- and second-line nilotinib, respectively.

Study details: Findings are from a retrospective analysis of adult patients with CML receiving either first-line nilotinib between January 2013 and December 2016 (n=87) or second-line nilotinib between January 2015 and December 2018 (n=103).

Disclosures: This publication was funded by Novartis Farma S.p.A. The authors declared no conflicts of interest.

Source: Perrone V et al. Ther Clin Risk Manag. 2021 Jun 8. doi: 10.2147/TCRM.S309342.

Key clinical point: Among patients with chronic myeloid leukemia (CML), the mean daily dose of nilotinib, either as the first- or second-line treatment prescribed in Italian clinical practice settings, was lower than the approved dose reported in the summary of product characteristics as the first- (600 mg daily) and second-line (800 mg daily) treatment.

Major finding: Based on the last determination of the BCR/ABL test, the mean daily nilotinib dose was 498.54 mg (mean treatment duration, 811 days) and 565.2 mg (mean treatment duration, 323.1 days) for patients treated with first- and second-line nilotinib, respectively.

Study details: Findings are from a retrospective analysis of adult patients with CML receiving either first-line nilotinib between January 2013 and December 2016 (n=87) or second-line nilotinib between January 2015 and December 2018 (n=103).

Disclosures: This publication was funded by Novartis Farma S.p.A. The authors declared no conflicts of interest.

Source: Perrone V et al. Ther Clin Risk Manag. 2021 Jun 8. doi: 10.2147/TCRM.S309342.

Key clinical point: Among patients with chronic myeloid leukemia (CML), the mean daily dose of nilotinib, either as the first- or second-line treatment prescribed in Italian clinical practice settings, was lower than the approved dose reported in the summary of product characteristics as the first- (600 mg daily) and second-line (800 mg daily) treatment.

Major finding: Based on the last determination of the BCR/ABL test, the mean daily nilotinib dose was 498.54 mg (mean treatment duration, 811 days) and 565.2 mg (mean treatment duration, 323.1 days) for patients treated with first- and second-line nilotinib, respectively.

Study details: Findings are from a retrospective analysis of adult patients with CML receiving either first-line nilotinib between January 2013 and December 2016 (n=87) or second-line nilotinib between January 2015 and December 2018 (n=103).

Disclosures: This publication was funded by Novartis Farma S.p.A. The authors declared no conflicts of interest.

Source: Perrone V et al. Ther Clin Risk Manag. 2021 Jun 8. doi: 10.2147/TCRM.S309342.

Key clinical point: Inotuzumab ozogamicin with bosutinib was well tolerated in patients with relapsed/refractory (R/R) lymphoid blast phase of chronic myeloid leukemia (CML-LBP) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL).

Major finding: Rates of complete response (CR)/CR with incomplete count recovery, complete cytogenic response, measurable residual disease negativity, and complete molecular response were 83%, 81%, 61%, and 56%, respectively. The 30-day mortality was 0%. During the median follow-up of 44 months, median event-free survival and overall survival were 7.7 and 13.5 months, respectively. No patients discontinued treatment because of toxicity, and no veno-occlusive disease was reported.

Study details: This was a phase 1/2 trial including 18 patients with R/R Ph+ALL (n=16) or CML-LBP (n=2). The maximum tolerated dose of bosutinib was 400 mg daily.

Disclosures: This study was funded by Pfizer, MD Anderson Cancer Center Support Grant, and the National Cancer Institute. Some investigators including the lead author reported ties with various pharmaceutical companies, including Pfizer.

Source: Jain N et al. Am J Hematol. 2021 May 15. doi: 10.1002/ajh.26238.

Key clinical point: Inotuzumab ozogamicin with bosutinib was well tolerated in patients with relapsed/refractory (R/R) lymphoid blast phase of chronic myeloid leukemia (CML-LBP) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL).

Major finding: Rates of complete response (CR)/CR with incomplete count recovery, complete cytogenic response, measurable residual disease negativity, and complete molecular response were 83%, 81%, 61%, and 56%, respectively. The 30-day mortality was 0%. During the median follow-up of 44 months, median event-free survival and overall survival were 7.7 and 13.5 months, respectively. No patients discontinued treatment because of toxicity, and no veno-occlusive disease was reported.

Study details: This was a phase 1/2 trial including 18 patients with R/R Ph+ALL (n=16) or CML-LBP (n=2). The maximum tolerated dose of bosutinib was 400 mg daily.

Disclosures: This study was funded by Pfizer, MD Anderson Cancer Center Support Grant, and the National Cancer Institute. Some investigators including the lead author reported ties with various pharmaceutical companies, including Pfizer.

Source: Jain N et al. Am J Hematol. 2021 May 15. doi: 10.1002/ajh.26238.

Key clinical point: Inotuzumab ozogamicin with bosutinib was well tolerated in patients with relapsed/refractory (R/R) lymphoid blast phase of chronic myeloid leukemia (CML-LBP) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL).

Major finding: Rates of complete response (CR)/CR with incomplete count recovery, complete cytogenic response, measurable residual disease negativity, and complete molecular response were 83%, 81%, 61%, and 56%, respectively. The 30-day mortality was 0%. During the median follow-up of 44 months, median event-free survival and overall survival were 7.7 and 13.5 months, respectively. No patients discontinued treatment because of toxicity, and no veno-occlusive disease was reported.

Study details: This was a phase 1/2 trial including 18 patients with R/R Ph+ALL (n=16) or CML-LBP (n=2). The maximum tolerated dose of bosutinib was 400 mg daily.

Disclosures: This study was funded by Pfizer, MD Anderson Cancer Center Support Grant, and the National Cancer Institute. Some investigators including the lead author reported ties with various pharmaceutical companies, including Pfizer.

Source: Jain N et al. Am J Hematol. 2021 May 15. doi: 10.1002/ajh.26238.

Key clinical point: Polymorphisms of CYP2A6 and ABCC4 genes were associated with a protective effect against the development of chronic myeloid leukemia (CML). These findings highlight the underlying genetic predisposition of individuals to develop CML.

Major finding: Individuals with the C allele of the rs28399433 polymorphism of CYP2A6 gene (odds ratio [OR], 0.33; 95% confidence interval [CI], 0.14-0.78; P = .008) and the CC genotype of the rs3742106 polymorphism of ABCC4 gene (OR, 0.30; 95% CI, 0.10-0.88; P = .020) had a significantly reduced susceptibility to CML vs. other genotypes.

Study details: This retrospective study assessed an admixed population of 269 individuals including 143 patients with CML and 126 healthy controls from the Amazon region of Brazil.

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

Source: Monte N et al. Mol Genet Genomic Med. 2021 May 29. doi: 10.1002/mgg3.1694.

Key clinical point: Polymorphisms of CYP2A6 and ABCC4 genes were associated with a protective effect against the development of chronic myeloid leukemia (CML). These findings highlight the underlying genetic predisposition of individuals to develop CML.

Major finding: Individuals with the C allele of the rs28399433 polymorphism of CYP2A6 gene (odds ratio [OR], 0.33; 95% confidence interval [CI], 0.14-0.78; P = .008) and the CC genotype of the rs3742106 polymorphism of ABCC4 gene (OR, 0.30; 95% CI, 0.10-0.88; P = .020) had a significantly reduced susceptibility to CML vs. other genotypes.

Study details: This retrospective study assessed an admixed population of 269 individuals including 143 patients with CML and 126 healthy controls from the Amazon region of Brazil.

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

Source: Monte N et al. Mol Genet Genomic Med. 2021 May 29. doi: 10.1002/mgg3.1694.

Key clinical point: Polymorphisms of CYP2A6 and ABCC4 genes were associated with a protective effect against the development of chronic myeloid leukemia (CML). These findings highlight the underlying genetic predisposition of individuals to develop CML.

Major finding: Individuals with the C allele of the rs28399433 polymorphism of CYP2A6 gene (odds ratio [OR], 0.33; 95% confidence interval [CI], 0.14-0.78; P = .008) and the CC genotype of the rs3742106 polymorphism of ABCC4 gene (OR, 0.30; 95% CI, 0.10-0.88; P = .020) had a significantly reduced susceptibility to CML vs. other genotypes.

Study details: This retrospective study assessed an admixed population of 269 individuals including 143 patients with CML and 126 healthy controls from the Amazon region of Brazil.

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

Source: Monte N et al. Mol Genet Genomic Med. 2021 May 29. doi: 10.1002/mgg3.1694.

Key clinical point: The Eutos long-term survival (ELTS) score appeared better at predicting overall survival (OS) in patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKIs), redefining the risk stratification obtained with the Sokal score. Patients defined as high risk by ELTS showed poorer OS, thereby warranting treatment intensification and close monitoring.

Major finding: A prognostic refinement was observed from the Sokal to the ELTS score in high and intermediate Sokal risk patients. In the high-risk Sokal group, 3-year OS ranged from 94.8% to 82.4% for patients considered at ‘true’ high risk. In the intermediate Sokal risk group, 3-year OS of high-risk patients was only 70.7% vs. 95.4% for low-risk and 87.9% for ‘true’ intermediate-risk patients.

Study details: Findings are from the analysis of 1,206 patients with CML from the GIMEMA observational study. Patients were treated with either imatinib (n=608) or second-generation TKIs, dasatinib, or nilotinib (n=598).

Disclosures: No source of funding was identified. Some investigators including the lead author reported honoraria from various pharmaceutical companies.

Source: Breccia M et al. Leukemia. 2021 May 17. doi: 10.1038/s41375-021-01292-4.

Key clinical point: The Eutos long-term survival (ELTS) score appeared better at predicting overall survival (OS) in patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKIs), redefining the risk stratification obtained with the Sokal score. Patients defined as high risk by ELTS showed poorer OS, thereby warranting treatment intensification and close monitoring.

Major finding: A prognostic refinement was observed from the Sokal to the ELTS score in high and intermediate Sokal risk patients. In the high-risk Sokal group, 3-year OS ranged from 94.8% to 82.4% for patients considered at ‘true’ high risk. In the intermediate Sokal risk group, 3-year OS of high-risk patients was only 70.7% vs. 95.4% for low-risk and 87.9% for ‘true’ intermediate-risk patients.

Study details: Findings are from the analysis of 1,206 patients with CML from the GIMEMA observational study. Patients were treated with either imatinib (n=608) or second-generation TKIs, dasatinib, or nilotinib (n=598).

Disclosures: No source of funding was identified. Some investigators including the lead author reported honoraria from various pharmaceutical companies.

Source: Breccia M et al. Leukemia. 2021 May 17. doi: 10.1038/s41375-021-01292-4.

Key clinical point: The Eutos long-term survival (ELTS) score appeared better at predicting overall survival (OS) in patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKIs), redefining the risk stratification obtained with the Sokal score. Patients defined as high risk by ELTS showed poorer OS, thereby warranting treatment intensification and close monitoring.

Major finding: A prognostic refinement was observed from the Sokal to the ELTS score in high and intermediate Sokal risk patients. In the high-risk Sokal group, 3-year OS ranged from 94.8% to 82.4% for patients considered at ‘true’ high risk. In the intermediate Sokal risk group, 3-year OS of high-risk patients was only 70.7% vs. 95.4% for low-risk and 87.9% for ‘true’ intermediate-risk patients.

Study details: Findings are from the analysis of 1,206 patients with CML from the GIMEMA observational study. Patients were treated with either imatinib (n=608) or second-generation TKIs, dasatinib, or nilotinib (n=598).

Disclosures: No source of funding was identified. Some investigators including the lead author reported honoraria from various pharmaceutical companies.

Source: Breccia M et al. Leukemia. 2021 May 17. doi: 10.1038/s41375-021-01292-4.

Key clinical point: In a large cohort of patients with newly diagnosed chronic-phase chronic myeloid leukemia (CML-CP) receiving frontline imatinib therapy, adolescents showed adverse disease features and shorter failure-free survival (FFS) compared with children, indicating distinct disease characteristics and outcomes between these pediatric groups.

Major finding: Adolescents vs. children presented with significantly higher white blood cell count (P = .033), basophil percentage in peripheral blood (P = .002), and prevalence of splenomegaly (P = .004). Children had a longer FFS vs. adolescents (hazard ratio, 2.36; P = .015).

Study details: Findings are from a retrospective analysis of 982 newly diagnosed patients with CML-CP, including 135 children, 189 adolescents, and 658 adults, who received imatinib as the first-line treatment within 6 months of diagnosis.

Disclosures: This study was funded by the National Natural Science Foundation of China. No author disclosures were reported.

Source: Dou X et al. Ann Hematol. 2021 Jun 5. doi: 10.1007/s00277-021-04544-6.

Key clinical point: In a large cohort of patients with newly diagnosed chronic-phase chronic myeloid leukemia (CML-CP) receiving frontline imatinib therapy, adolescents showed adverse disease features and shorter failure-free survival (FFS) compared with children, indicating distinct disease characteristics and outcomes between these pediatric groups.

Major finding: Adolescents vs. children presented with significantly higher white blood cell count (P = .033), basophil percentage in peripheral blood (P = .002), and prevalence of splenomegaly (P = .004). Children had a longer FFS vs. adolescents (hazard ratio, 2.36; P = .015).

Study details: Findings are from a retrospective analysis of 982 newly diagnosed patients with CML-CP, including 135 children, 189 adolescents, and 658 adults, who received imatinib as the first-line treatment within 6 months of diagnosis.

Disclosures: This study was funded by the National Natural Science Foundation of China. No author disclosures were reported.

Source: Dou X et al. Ann Hematol. 2021 Jun 5. doi: 10.1007/s00277-021-04544-6.

Key clinical point: In a large cohort of patients with newly diagnosed chronic-phase chronic myeloid leukemia (CML-CP) receiving frontline imatinib therapy, adolescents showed adverse disease features and shorter failure-free survival (FFS) compared with children, indicating distinct disease characteristics and outcomes between these pediatric groups.

Major finding: Adolescents vs. children presented with significantly higher white blood cell count (P = .033), basophil percentage in peripheral blood (P = .002), and prevalence of splenomegaly (P = .004). Children had a longer FFS vs. adolescents (hazard ratio, 2.36; P = .015).

Study details: Findings are from a retrospective analysis of 982 newly diagnosed patients with CML-CP, including 135 children, 189 adolescents, and 658 adults, who received imatinib as the first-line treatment within 6 months of diagnosis.

Disclosures: This study was funded by the National Natural Science Foundation of China. No author disclosures were reported.

Source: Dou X et al. Ann Hematol. 2021 Jun 5. doi: 10.1007/s00277-021-04544-6.

Key clinical point: Administration of a single dose of SARS-CoV-2 BNT162b2 vaccine (Pfizer-BioNTech) led to seroconversion and T-cell response in most patients with chronic-phase chronic myeloid leukemia (CML-CP), with neutralizing antibody responses in all.

Major finding: After 3 weeks of BNT162b2 administration, anti-Spike immunoglobulin G and neutralizing antibodies were observed in 87.5% and 100% of patients, respectively. A memory T-cell response was observed in 93.3% of patients, with a polyfunctional cytokine response in either CD4⁺ or CD8⁺ T cells in 80% of patients.

Study details: Findings are from an analysis of 16 adult patients with CML-CP who received the first injection of 30 mg BNT162b2.

Disclosures: This study was funded by King’s Together Rapid COVID-19 Call Award, Huo Family Foundation Award, Chronic Disease Research Foundation award, Wellcome Trust Investigator Award, MRC-KCL Doctoral Training Partnership in Biomedical Sciences, Fondation Dormeur (Vaduz), Blood Cancer UK, LifeArc, Cancer Research UK, and King’s Health Partners Centre.

Source: Harrington P et al. Br J Haematol. 2021 June 3. doi: 10.1111/bjh.17568.

Key clinical point: Administration of a single dose of SARS-CoV-2 BNT162b2 vaccine (Pfizer-BioNTech) led to seroconversion and T-cell response in most patients with chronic-phase chronic myeloid leukemia (CML-CP), with neutralizing antibody responses in all.

Major finding: After 3 weeks of BNT162b2 administration, anti-Spike immunoglobulin G and neutralizing antibodies were observed in 87.5% and 100% of patients, respectively. A memory T-cell response was observed in 93.3% of patients, with a polyfunctional cytokine response in either CD4⁺ or CD8⁺ T cells in 80% of patients.

Study details: Findings are from an analysis of 16 adult patients with CML-CP who received the first injection of 30 mg BNT162b2.

Disclosures: This study was funded by King’s Together Rapid COVID-19 Call Award, Huo Family Foundation Award, Chronic Disease Research Foundation award, Wellcome Trust Investigator Award, MRC-KCL Doctoral Training Partnership in Biomedical Sciences, Fondation Dormeur (Vaduz), Blood Cancer UK, LifeArc, Cancer Research UK, and King’s Health Partners Centre.

Source: Harrington P et al. Br J Haematol. 2021 June 3. doi: 10.1111/bjh.17568.

Key clinical point: Administration of a single dose of SARS-CoV-2 BNT162b2 vaccine (Pfizer-BioNTech) led to seroconversion and T-cell response in most patients with chronic-phase chronic myeloid leukemia (CML-CP), with neutralizing antibody responses in all.

Major finding: After 3 weeks of BNT162b2 administration, anti-Spike immunoglobulin G and neutralizing antibodies were observed in 87.5% and 100% of patients, respectively. A memory T-cell response was observed in 93.3% of patients, with a polyfunctional cytokine response in either CD4⁺ or CD8⁺ T cells in 80% of patients.

Study details: Findings are from an analysis of 16 adult patients with CML-CP who received the first injection of 30 mg BNT162b2.

Disclosures: This study was funded by King’s Together Rapid COVID-19 Call Award, Huo Family Foundation Award, Chronic Disease Research Foundation award, Wellcome Trust Investigator Award, MRC-KCL Doctoral Training Partnership in Biomedical Sciences, Fondation Dormeur (Vaduz), Blood Cancer UK, LifeArc, Cancer Research UK, and King’s Health Partners Centre.

Source: Harrington P et al. Br J Haematol. 2021 June 3. doi: 10.1111/bjh.17568.