AML

Key clinical point: Patients with TP53-mutated acute myeloid leukemia (AML) receiving a 10-day regimen of decitabine with venetoclax (DEC10-VEN) experienced inferior response rates and survival vs those with wild-type TP53 AML.

Major finding: Patients with TP53-mutant vs wild-type TP53 AML had significantly lower overall survival (hazard ratio [HR], 4.67; P < .0001), relapse-free survival (HR, 4.80; P < .001), overall response rate (66% vs 89%; P = .002), and complete response (CR)/CR with incomplete hematologic recovery rate (57% vs 77%; P = .029).

Study details: Findings are from a post hoc analysis of a phase 2 trial including 118 patients with newly diagnosed AML unfit for intensive chemotherapy or with secondary or relapsed/refractory AML receiving frontline therapy with DEC10-VEN. Overall, 35 patients had TP53-mutated AML.

Disclosures: This study was supported by grants from the National Cancer Institute and the National Institutes of Health. Some investigators reported ties with various pharmaceutical companies.

Source: Kim K et al. Cancer. 2021 Jul 13. doi: 10.1002/cncr.33689.

Key clinical point: Patients with TP53-mutated acute myeloid leukemia (AML) receiving a 10-day regimen of decitabine with venetoclax (DEC10-VEN) experienced inferior response rates and survival vs those with wild-type TP53 AML.

Major finding: Patients with TP53-mutant vs wild-type TP53 AML had significantly lower overall survival (hazard ratio [HR], 4.67; P < .0001), relapse-free survival (HR, 4.80; P < .001), overall response rate (66% vs 89%; P = .002), and complete response (CR)/CR with incomplete hematologic recovery rate (57% vs 77%; P = .029).

Study details: Findings are from a post hoc analysis of a phase 2 trial including 118 patients with newly diagnosed AML unfit for intensive chemotherapy or with secondary or relapsed/refractory AML receiving frontline therapy with DEC10-VEN. Overall, 35 patients had TP53-mutated AML.

Disclosures: This study was supported by grants from the National Cancer Institute and the National Institutes of Health. Some investigators reported ties with various pharmaceutical companies.

Source: Kim K et al. Cancer. 2021 Jul 13. doi: 10.1002/cncr.33689.

Key clinical point: Patients with TP53-mutated acute myeloid leukemia (AML) receiving a 10-day regimen of decitabine with venetoclax (DEC10-VEN) experienced inferior response rates and survival vs those with wild-type TP53 AML.

Major finding: Patients with TP53-mutant vs wild-type TP53 AML had significantly lower overall survival (hazard ratio [HR], 4.67; P < .0001), relapse-free survival (HR, 4.80; P < .001), overall response rate (66% vs 89%; P = .002), and complete response (CR)/CR with incomplete hematologic recovery rate (57% vs 77%; P = .029).

Study details: Findings are from a post hoc analysis of a phase 2 trial including 118 patients with newly diagnosed AML unfit for intensive chemotherapy or with secondary or relapsed/refractory AML receiving frontline therapy with DEC10-VEN. Overall, 35 patients had TP53-mutated AML.

Disclosures: This study was supported by grants from the National Cancer Institute and the National Institutes of Health. Some investigators reported ties with various pharmaceutical companies.

Source: Kim K et al. Cancer. 2021 Jul 13. doi: 10.1002/cncr.33689.

Key clinical point: Addition of oblimersen sodium (G3139) to standard chemotherapy did not improve clinical outcomes vs standard chemotherapy alone in previously untreated older patients with acute myeloid leukemia (AML).

Major finding: No statistically significant differences were observed in complete remission rates (P = .53), median overall survival (1-sided log-rank P = .13), median event-free survival (P = .80), median disease-free survival (P = .26), and early death rates (P = .81) in the G3139 vs standard chemotherapy arm. No added toxicities were observed with G3139 vs standard chemotherapy alone.

Study details: Findings are from phase 3 Cancer and Leukemia Group B 10201 trial including 506 untreated patients with AML aged at least 60 years. Patients were randomly assigned to receive standard intensive cytarabine/daunorubicin induction chemotherapy and high-dose cytarabine consolidation with (n=254) or without (n=252) G3139.

Disclosures: This work was supported by the National Cancer Institute, National Institutes of Health, and Deltec Inc. Some investigators including the lead author reported ties with various pharmaceutical companies.

Source: Walker AR et al. Blood Adv. 2021 Jul 12. doi: 10.1182/bloodadvances.2021004233.

Key clinical point: Addition of oblimersen sodium (G3139) to standard chemotherapy did not improve clinical outcomes vs standard chemotherapy alone in previously untreated older patients with acute myeloid leukemia (AML).

Major finding: No statistically significant differences were observed in complete remission rates (P = .53), median overall survival (1-sided log-rank P = .13), median event-free survival (P = .80), median disease-free survival (P = .26), and early death rates (P = .81) in the G3139 vs standard chemotherapy arm. No added toxicities were observed with G3139 vs standard chemotherapy alone.

Study details: Findings are from phase 3 Cancer and Leukemia Group B 10201 trial including 506 untreated patients with AML aged at least 60 years. Patients were randomly assigned to receive standard intensive cytarabine/daunorubicin induction chemotherapy and high-dose cytarabine consolidation with (n=254) or without (n=252) G3139.

Disclosures: This work was supported by the National Cancer Institute, National Institutes of Health, and Deltec Inc. Some investigators including the lead author reported ties with various pharmaceutical companies.

Source: Walker AR et al. Blood Adv. 2021 Jul 12. doi: 10.1182/bloodadvances.2021004233.

Key clinical point: Addition of oblimersen sodium (G3139) to standard chemotherapy did not improve clinical outcomes vs standard chemotherapy alone in previously untreated older patients with acute myeloid leukemia (AML).

Major finding: No statistically significant differences were observed in complete remission rates (P = .53), median overall survival (1-sided log-rank P = .13), median event-free survival (P = .80), median disease-free survival (P = .26), and early death rates (P = .81) in the G3139 vs standard chemotherapy arm. No added toxicities were observed with G3139 vs standard chemotherapy alone.

Study details: Findings are from phase 3 Cancer and Leukemia Group B 10201 trial including 506 untreated patients with AML aged at least 60 years. Patients were randomly assigned to receive standard intensive cytarabine/daunorubicin induction chemotherapy and high-dose cytarabine consolidation with (n=254) or without (n=252) G3139.

Disclosures: This work was supported by the National Cancer Institute, National Institutes of Health, and Deltec Inc. Some investigators including the lead author reported ties with various pharmaceutical companies.

Source: Walker AR et al. Blood Adv. 2021 Jul 12. doi: 10.1182/bloodadvances.2021004233.

Key clinical point: Addition of venetoclax to intensive chemotherapy with cladribine, idarubicin, and high-dose cytarabine (CLIA regimen) was safe and feasible as frontline therapy in patients aged 65 years or younger with newly diagnosed acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS).

Major finding: Overall, 94% (95% confidence interval [CI], 83%-98%) had a composite complete response and 82% (95% CI, 68%-92%) achieved measurable residual disease negativity. At 12 months, the rates of duration of response, overall survival, and event-free survival were 74% (95% CI, 60%-92%), 85% (95% CI, 75%-97%), and 68% (95% CI, 54%-85%), respectively. The most common grade 3 or worse adverse events were febrile neutropenia (84%), infection (12%), and alanine aminotransferase elevations (12%).

Study details: Findings are from a cohort study from the phase 2 CLIA trial including 50 patients (age, 18-65 years) with newly diagnosed AML (90%), MDS (8%), or mixed phenotype acute leukemia (2%).

Disclosures: This study was supported by grants from the MD Anderson Cancer Center. Some investigators including the lead author reported ties with various pharmaceutical companies.

Source: Kadia TM et al. Lancet Haematol. 2021 Aug 1. doi: 10.1016/S2352-3026(21)00192-7.

Key clinical point: Addition of venetoclax to intensive chemotherapy with cladribine, idarubicin, and high-dose cytarabine (CLIA regimen) was safe and feasible as frontline therapy in patients aged 65 years or younger with newly diagnosed acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS).

Major finding: Overall, 94% (95% confidence interval [CI], 83%-98%) had a composite complete response and 82% (95% CI, 68%-92%) achieved measurable residual disease negativity. At 12 months, the rates of duration of response, overall survival, and event-free survival were 74% (95% CI, 60%-92%), 85% (95% CI, 75%-97%), and 68% (95% CI, 54%-85%), respectively. The most common grade 3 or worse adverse events were febrile neutropenia (84%), infection (12%), and alanine aminotransferase elevations (12%).

Study details: Findings are from a cohort study from the phase 2 CLIA trial including 50 patients (age, 18-65 years) with newly diagnosed AML (90%), MDS (8%), or mixed phenotype acute leukemia (2%).

Disclosures: This study was supported by grants from the MD Anderson Cancer Center. Some investigators including the lead author reported ties with various pharmaceutical companies.

Source: Kadia TM et al. Lancet Haematol. 2021 Aug 1. doi: 10.1016/S2352-3026(21)00192-7.

Key clinical point: Addition of venetoclax to intensive chemotherapy with cladribine, idarubicin, and high-dose cytarabine (CLIA regimen) was safe and feasible as frontline therapy in patients aged 65 years or younger with newly diagnosed acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS).

Major finding: Overall, 94% (95% confidence interval [CI], 83%-98%) had a composite complete response and 82% (95% CI, 68%-92%) achieved measurable residual disease negativity. At 12 months, the rates of duration of response, overall survival, and event-free survival were 74% (95% CI, 60%-92%), 85% (95% CI, 75%-97%), and 68% (95% CI, 54%-85%), respectively. The most common grade 3 or worse adverse events were febrile neutropenia (84%), infection (12%), and alanine aminotransferase elevations (12%).

Study details: Findings are from a cohort study from the phase 2 CLIA trial including 50 patients (age, 18-65 years) with newly diagnosed AML (90%), MDS (8%), or mixed phenotype acute leukemia (2%).

Disclosures: This study was supported by grants from the MD Anderson Cancer Center. Some investigators including the lead author reported ties with various pharmaceutical companies.

Source: Kadia TM et al. Lancet Haematol. 2021 Aug 1. doi: 10.1016/S2352-3026(21)00192-7.

CPX-351 is a liposomal cytarabine and daunorubicin. It was FDA approved in 2017 for the treatment of patients with newly diagnosed therapy-related AML (t-AML) or AML with myelodysplasia-related changes (AML-MRC). The approval was based on the results from a randomized trial comparing CPX-351 vs standard 7 +3 chemotherapy in patients older that 65 with t-AML or AML-MRC. The 5-year results from that study were recently published by Lancet et al. At 5 years of follow-up, CPX-351 continued to show benefit in older patients with t-AML or AML-MRC vs standard chemotherapy with cytarabine for 7 days and daunorubicin for 3 days (7+3) . The median OS in favor of CPX-351 vs 7+3 group was maintained (hazard ratio, 0.70; 95% confidence interval [CI], 0.55-0.91). At 5 years, survival estimates were higher for CPX-351 vs 7+3 (18% [95% CI, 12%-25%] vs 8% [95% CI, 4%-13%]). Overall, 5% of deaths in both groups were considered related to the study treatment. Overall, more patients treated with CPX-351 were able to proceed to stem cell transplantation (SCT) compared to those treated with 7 + 3 (35% vs 25%).

The 3-year overall survival from SCT was 56% vs 23% for patients treated with CPX-351 vs 7 +3. Of the responding patients who did not proceed to SCT, only 3 patients were alive at 5 years. Although this data is encouraging, it demonstrates that we have a long way to go to improve the outcome of these patients. In addition, more patients who achieve remission should proceed to SCT in order to improve the survival of this patient population (Lancet JE et al). In terms of supportive care during induction chemotherapy, two published studies this month evaluated two approaches to aiming to decrease the morbidity from infections: prospective monitoring for fungal infections and the use of romyelocel with G-CSF. Prospectively monitoring for fungal infections was performed as an observation study imbedded within a phase 3 Children’s Oncology Group trial (ACCL0933). The study included 471 patients with AML (age, 3 months-30 years) receiving fluconazole (n=235) or caspofungin (n=236).

Twice-weekly surveillance with galactomannan enzyme immunoassay (GM-EIA) and b-D-glucan (BDG) assay were performed in all patients. The negative predictive value was greater than 99% for an individual or combination of GM-EIA and BDG assays. However, true positive results were not observed in any sample collected within 7 days of an invasive aspergillosis/candidiasis diagnosis, resulting in sensitivity and positive predictive value for each test of 0%. This approach was ineffective at detecting invasive fungal diseases (IFDs) in children, adolescents, and young adults with acute myeloid leukemia (AML) receiving antifungal prophylaxis (Fisher BT et al).

A different approach to reduce infection morbidity and mortality during induction chemotherapy is the administration of romyelocel. Myeloid progenitor cells are cells that can produce granulocytes but have no long-term reconstitution capability.  Romyelocel is a cryopreserved product, of MPC manufactured by ex vivo expansion of CD34⁺ hematopoietic stem cells. Romyelocel is capable of producing granulocytes, and thereby may reduce the severity or duration of neutropenic fevers. This phase 2 study included 163 patients with de novo AML receiving induction chemotherapy. Evaluable patients (n=120) were randomly assigned to receive either romyelocel-L plus G-CSF (n=59) or G-CSF monotherapy (n=61). From days 15 to 28, romyelocel-L plus G-CSF vs G-CSF monotherapy significantly reduced the mean duration of febrile episodes (2.36 days vs 3.90 days; P = .02) and incidence of infections (6.8% vs 27.9%; P = .0013). Length of hospitalization was significantly shorter in the romyelocel-L plus G-CSF vs G-CSF monotherapy group (25.5 days vs 28.7 days; P = .002). These results are encouraging, and a phase III trial is suggested by the authors. (Desai PM et al).

Finally, a study by MDACC reported disappointing results with the use of venetoclax in patients with tp53 mutation. Findings are from a retrospective analysis of 238 patients with newly diagnosed TP53-mutated AML treated with either VEN-based (n=58) or non-VEN-based (n=180) therapies. The addition of venetoclax to standard treatment regimens (VEN-based) did not improve clinical outcomes in patients with TP53-mutated acute myeloid leukemia (AML), highlighting the need for novel therapies in this patient population. Overall, there was no significant differences in overall survival (median, 5.7 months vs 6.6 months; P = .4), relapse-free survival (median, 3.5 months vs 4.7 months; P = .43), 4-week mortality (7% vs 10%; P = .5), and 8-week mortality (22% vs 17%; P = .4) in patients receiving VEN-based vs non-VEN-based therapies (Venugopal S et al). Clearly, better therapies are needed for this patient population.

CPX-351 is a liposomal cytarabine and daunorubicin. It was FDA approved in 2017 for the treatment of patients with newly diagnosed therapy-related AML (t-AML) or AML with myelodysplasia-related changes (AML-MRC). The approval was based on the results from a randomized trial comparing CPX-351 vs standard 7 +3 chemotherapy in patients older that 65 with t-AML or AML-MRC. The 5-year results from that study were recently published by Lancet et al. At 5 years of follow-up, CPX-351 continued to show benefit in older patients with t-AML or AML-MRC vs standard chemotherapy with cytarabine for 7 days and daunorubicin for 3 days (7+3) . The median OS in favor of CPX-351 vs 7+3 group was maintained (hazard ratio, 0.70; 95% confidence interval [CI], 0.55-0.91). At 5 years, survival estimates were higher for CPX-351 vs 7+3 (18% [95% CI, 12%-25%] vs 8% [95% CI, 4%-13%]). Overall, 5% of deaths in both groups were considered related to the study treatment. Overall, more patients treated with CPX-351 were able to proceed to stem cell transplantation (SCT) compared to those treated with 7 + 3 (35% vs 25%).

The 3-year overall survival from SCT was 56% vs 23% for patients treated with CPX-351 vs 7 +3. Of the responding patients who did not proceed to SCT, only 3 patients were alive at 5 years. Although this data is encouraging, it demonstrates that we have a long way to go to improve the outcome of these patients. In addition, more patients who achieve remission should proceed to SCT in order to improve the survival of this patient population (Lancet JE et al). In terms of supportive care during induction chemotherapy, two published studies this month evaluated two approaches to aiming to decrease the morbidity from infections: prospective monitoring for fungal infections and the use of romyelocel with G-CSF. Prospectively monitoring for fungal infections was performed as an observation study imbedded within a phase 3 Children’s Oncology Group trial (ACCL0933). The study included 471 patients with AML (age, 3 months-30 years) receiving fluconazole (n=235) or caspofungin (n=236).

Twice-weekly surveillance with galactomannan enzyme immunoassay (GM-EIA) and b-D-glucan (BDG) assay were performed in all patients. The negative predictive value was greater than 99% for an individual or combination of GM-EIA and BDG assays. However, true positive results were not observed in any sample collected within 7 days of an invasive aspergillosis/candidiasis diagnosis, resulting in sensitivity and positive predictive value for each test of 0%. This approach was ineffective at detecting invasive fungal diseases (IFDs) in children, adolescents, and young adults with acute myeloid leukemia (AML) receiving antifungal prophylaxis (Fisher BT et al).

A different approach to reduce infection morbidity and mortality during induction chemotherapy is the administration of romyelocel. Myeloid progenitor cells are cells that can produce granulocytes but have no long-term reconstitution capability.  Romyelocel is a cryopreserved product, of MPC manufactured by ex vivo expansion of CD34⁺ hematopoietic stem cells. Romyelocel is capable of producing granulocytes, and thereby may reduce the severity or duration of neutropenic fevers. This phase 2 study included 163 patients with de novo AML receiving induction chemotherapy. Evaluable patients (n=120) were randomly assigned to receive either romyelocel-L plus G-CSF (n=59) or G-CSF monotherapy (n=61). From days 15 to 28, romyelocel-L plus G-CSF vs G-CSF monotherapy significantly reduced the mean duration of febrile episodes (2.36 days vs 3.90 days; P = .02) and incidence of infections (6.8% vs 27.9%; P = .0013). Length of hospitalization was significantly shorter in the romyelocel-L plus G-CSF vs G-CSF monotherapy group (25.5 days vs 28.7 days; P = .002). These results are encouraging, and a phase III trial is suggested by the authors. (Desai PM et al).

Finally, a study by MDACC reported disappointing results with the use of venetoclax in patients with tp53 mutation. Findings are from a retrospective analysis of 238 patients with newly diagnosed TP53-mutated AML treated with either VEN-based (n=58) or non-VEN-based (n=180) therapies. The addition of venetoclax to standard treatment regimens (VEN-based) did not improve clinical outcomes in patients with TP53-mutated acute myeloid leukemia (AML), highlighting the need for novel therapies in this patient population. Overall, there was no significant differences in overall survival (median, 5.7 months vs 6.6 months; P = .4), relapse-free survival (median, 3.5 months vs 4.7 months; P = .43), 4-week mortality (7% vs 10%; P = .5), and 8-week mortality (22% vs 17%; P = .4) in patients receiving VEN-based vs non-VEN-based therapies (Venugopal S et al). Clearly, better therapies are needed for this patient population.

CPX-351 is a liposomal cytarabine and daunorubicin. It was FDA approved in 2017 for the treatment of patients with newly diagnosed therapy-related AML (t-AML) or AML with myelodysplasia-related changes (AML-MRC). The approval was based on the results from a randomized trial comparing CPX-351 vs standard 7 +3 chemotherapy in patients older that 65 with t-AML or AML-MRC. The 5-year results from that study were recently published by Lancet et al. At 5 years of follow-up, CPX-351 continued to show benefit in older patients with t-AML or AML-MRC vs standard chemotherapy with cytarabine for 7 days and daunorubicin for 3 days (7+3) . The median OS in favor of CPX-351 vs 7+3 group was maintained (hazard ratio, 0.70; 95% confidence interval [CI], 0.55-0.91). At 5 years, survival estimates were higher for CPX-351 vs 7+3 (18% [95% CI, 12%-25%] vs 8% [95% CI, 4%-13%]). Overall, 5% of deaths in both groups were considered related to the study treatment. Overall, more patients treated with CPX-351 were able to proceed to stem cell transplantation (SCT) compared to those treated with 7 + 3 (35% vs 25%).

The 3-year overall survival from SCT was 56% vs 23% for patients treated with CPX-351 vs 7 +3. Of the responding patients who did not proceed to SCT, only 3 patients were alive at 5 years. Although this data is encouraging, it demonstrates that we have a long way to go to improve the outcome of these patients. In addition, more patients who achieve remission should proceed to SCT in order to improve the survival of this patient population (Lancet JE et al). In terms of supportive care during induction chemotherapy, two published studies this month evaluated two approaches to aiming to decrease the morbidity from infections: prospective monitoring for fungal infections and the use of romyelocel with G-CSF. Prospectively monitoring for fungal infections was performed as an observation study imbedded within a phase 3 Children’s Oncology Group trial (ACCL0933). The study included 471 patients with AML (age, 3 months-30 years) receiving fluconazole (n=235) or caspofungin (n=236).

Twice-weekly surveillance with galactomannan enzyme immunoassay (GM-EIA) and b-D-glucan (BDG) assay were performed in all patients. The negative predictive value was greater than 99% for an individual or combination of GM-EIA and BDG assays. However, true positive results were not observed in any sample collected within 7 days of an invasive aspergillosis/candidiasis diagnosis, resulting in sensitivity and positive predictive value for each test of 0%. This approach was ineffective at detecting invasive fungal diseases (IFDs) in children, adolescents, and young adults with acute myeloid leukemia (AML) receiving antifungal prophylaxis (Fisher BT et al).

A different approach to reduce infection morbidity and mortality during induction chemotherapy is the administration of romyelocel. Myeloid progenitor cells are cells that can produce granulocytes but have no long-term reconstitution capability.  Romyelocel is a cryopreserved product, of MPC manufactured by ex vivo expansion of CD34⁺ hematopoietic stem cells. Romyelocel is capable of producing granulocytes, and thereby may reduce the severity or duration of neutropenic fevers. This phase 2 study included 163 patients with de novo AML receiving induction chemotherapy. Evaluable patients (n=120) were randomly assigned to receive either romyelocel-L plus G-CSF (n=59) or G-CSF monotherapy (n=61). From days 15 to 28, romyelocel-L plus G-CSF vs G-CSF monotherapy significantly reduced the mean duration of febrile episodes (2.36 days vs 3.90 days; P = .02) and incidence of infections (6.8% vs 27.9%; P = .0013). Length of hospitalization was significantly shorter in the romyelocel-L plus G-CSF vs G-CSF monotherapy group (25.5 days vs 28.7 days; P = .002). These results are encouraging, and a phase III trial is suggested by the authors. (Desai PM et al).

Finally, a study by MDACC reported disappointing results with the use of venetoclax in patients with tp53 mutation. Findings are from a retrospective analysis of 238 patients with newly diagnosed TP53-mutated AML treated with either VEN-based (n=58) or non-VEN-based (n=180) therapies. The addition of venetoclax to standard treatment regimens (VEN-based) did not improve clinical outcomes in patients with TP53-mutated acute myeloid leukemia (AML), highlighting the need for novel therapies in this patient population. Overall, there was no significant differences in overall survival (median, 5.7 months vs 6.6 months; P = .4), relapse-free survival (median, 3.5 months vs 4.7 months; P = .43), 4-week mortality (7% vs 10%; P = .5), and 8-week mortality (22% vs 17%; P = .4) in patients receiving VEN-based vs non-VEN-based therapies (Venugopal S et al). Clearly, better therapies are needed for this patient population.

Key clinical point: Among human leukocyte antigen (HLA)-matched donor-recipient pairs (DRPs) who underwent unrelated donor hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML), higher inhibitory and missing killer immunoglobulin-like receptors (KIRs) were associated with a reduced risk for relapse, but without any survival advantage.

Major finding: Higher inhibitory KIR (subhazard ratio [SHR], 0.86; P = .01) and missing KIR (SHR, 0.84; P = .02) scores were associated with a reduced risk for relapse. Patients with inhibitory ‘maxima’ (IM)-KIR of 5 had a lower risk for relapse (SHR, 0.80; P = .004) vs those with IM of less than 5. However, increased transplant-related mortality (SHR, 1.32; P less than .05) was observed in 8/8 HLA-matched DRPs with IM 5 vs less than 5.

Study details: Findings are from a retrospective analysis of 2,365 DRPs who underwent unrelated donor HCT with HLA match grade of 8/8 (85%) or 7/8 for early- or intermediate-risk AML.

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

Source: Krieger E et al. Bone Marrow Transplant. 2021 Jul 7. doi: 10.1038/s41409-021-01393-9.

Key clinical point: Among human leukocyte antigen (HLA)-matched donor-recipient pairs (DRPs) who underwent unrelated donor hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML), higher inhibitory and missing killer immunoglobulin-like receptors (KIRs) were associated with a reduced risk for relapse, but without any survival advantage.

Major finding: Higher inhibitory KIR (subhazard ratio [SHR], 0.86; P = .01) and missing KIR (SHR, 0.84; P = .02) scores were associated with a reduced risk for relapse. Patients with inhibitory ‘maxima’ (IM)-KIR of 5 had a lower risk for relapse (SHR, 0.80; P = .004) vs those with IM of less than 5. However, increased transplant-related mortality (SHR, 1.32; P less than .05) was observed in 8/8 HLA-matched DRPs with IM 5 vs less than 5.

Study details: Findings are from a retrospective analysis of 2,365 DRPs who underwent unrelated donor HCT with HLA match grade of 8/8 (85%) or 7/8 for early- or intermediate-risk AML.

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

Source: Krieger E et al. Bone Marrow Transplant. 2021 Jul 7. doi: 10.1038/s41409-021-01393-9.

Key clinical point: Among human leukocyte antigen (HLA)-matched donor-recipient pairs (DRPs) who underwent unrelated donor hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML), higher inhibitory and missing killer immunoglobulin-like receptors (KIRs) were associated with a reduced risk for relapse, but without any survival advantage.

Major finding: Higher inhibitory KIR (subhazard ratio [SHR], 0.86; P = .01) and missing KIR (SHR, 0.84; P = .02) scores were associated with a reduced risk for relapse. Patients with inhibitory ‘maxima’ (IM)-KIR of 5 had a lower risk for relapse (SHR, 0.80; P = .004) vs those with IM of less than 5. However, increased transplant-related mortality (SHR, 1.32; P less than .05) was observed in 8/8 HLA-matched DRPs with IM 5 vs less than 5.

Study details: Findings are from a retrospective analysis of 2,365 DRPs who underwent unrelated donor HCT with HLA match grade of 8/8 (85%) or 7/8 for early- or intermediate-risk AML.

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

Source: Krieger E et al. Bone Marrow Transplant. 2021 Jul 7. doi: 10.1038/s41409-021-01393-9.

Key clinical point: High PRR34 antisense RNA 1 (PRR34-AS1) expression was associated with poor chemotherapeutic response and prognosis in patients with acute myeloid leukemia (AML).

Major finding: Patients with high (n=42) vs low (n=41) expression of PRR34-AS1 had a significantly lower rate of complete remission (CR; 37.1% vs 72.7%; P = .004) and shorter overall survival (P = .002). PRR34-AS1 was an independent factor affecting CR in patients with whole AML (odds ratio [OR], 0.282; P = .032), non-acute promyelocytic leukemia-AML (OR, 0.253; P = .039), and cytogenetically normal AML (OR, 0.210; P = .033).

Study details: This study assessed PRR34-AS1 expression in 84 adult patients with newly diagnosed AML and 29 healthy controls.

Disclosures: This study was supported by the National Natural Science Foundation of China, Medical Innovation Team of Jiangsu Province, Zhenjiang Clinical Research Center of Hematology, Social Development Foundation of Zhenjiang, and Scientific Research Project of the Fifth 169 Project of Zhenjiang. The authors declared no conflicts of interest.

Source: Nan FY et al. Cancer Med. 2021 Jul 5. doi: 10.1002/cam4.4085.

Key clinical point: High PRR34 antisense RNA 1 (PRR34-AS1) expression was associated with poor chemotherapeutic response and prognosis in patients with acute myeloid leukemia (AML).

Major finding: Patients with high (n=42) vs low (n=41) expression of PRR34-AS1 had a significantly lower rate of complete remission (CR; 37.1% vs 72.7%; P = .004) and shorter overall survival (P = .002). PRR34-AS1 was an independent factor affecting CR in patients with whole AML (odds ratio [OR], 0.282; P = .032), non-acute promyelocytic leukemia-AML (OR, 0.253; P = .039), and cytogenetically normal AML (OR, 0.210; P = .033).

Study details: This study assessed PRR34-AS1 expression in 84 adult patients with newly diagnosed AML and 29 healthy controls.

Disclosures: This study was supported by the National Natural Science Foundation of China, Medical Innovation Team of Jiangsu Province, Zhenjiang Clinical Research Center of Hematology, Social Development Foundation of Zhenjiang, and Scientific Research Project of the Fifth 169 Project of Zhenjiang. The authors declared no conflicts of interest.

Source: Nan FY et al. Cancer Med. 2021 Jul 5. doi: 10.1002/cam4.4085.

Key clinical point: High PRR34 antisense RNA 1 (PRR34-AS1) expression was associated with poor chemotherapeutic response and prognosis in patients with acute myeloid leukemia (AML).

Major finding: Patients with high (n=42) vs low (n=41) expression of PRR34-AS1 had a significantly lower rate of complete remission (CR; 37.1% vs 72.7%; P = .004) and shorter overall survival (P = .002). PRR34-AS1 was an independent factor affecting CR in patients with whole AML (odds ratio [OR], 0.282; P = .032), non-acute promyelocytic leukemia-AML (OR, 0.253; P = .039), and cytogenetically normal AML (OR, 0.210; P = .033).

Study details: This study assessed PRR34-AS1 expression in 84 adult patients with newly diagnosed AML and 29 healthy controls.

Disclosures: This study was supported by the National Natural Science Foundation of China, Medical Innovation Team of Jiangsu Province, Zhenjiang Clinical Research Center of Hematology, Social Development Foundation of Zhenjiang, and Scientific Research Project of the Fifth 169 Project of Zhenjiang. The authors declared no conflicts of interest.

Source: Nan FY et al. Cancer Med. 2021 Jul 5. doi: 10.1002/cam4.4085.

Key clinical point: The addition of venetoclax to standard treatment regimens (VEN-based) did not improve clinical outcomes in patients with TP53-mutated acute myeloid leukemia (AML), highlighting the need for novel therapies in this patient population.

Major finding: Overall, no significant differences were observed in the rates of composite complete remission (P = .18), overall survival (median, 5.7 months vs 6.6 months; P = .4), relapse-free survival (median, 3.5 months vs 4.7 months; P = .43), 4-week mortality (7% vs 10%; P = .5), and 8-week mortality (22% vs 17%; P = .4) in patients receiving VEN-based vs non-VEN-based therapies.

Study details: Findings are from a retrospective analysis of 238 patients with newly diagnosed TP53-mutated AML treated with either VEN-based (n=58) or non-VEN-based (n=180) therapies.

Disclosures: This study was supported partly by the University of Texas MD Anderson Cancer Center Support Grant from the National Cancer Institute. Some investigators reported ties with various pharmaceutical companies.

Source: Venugopal S et al. Cancer. 2021 Jun 28. doi: 10.1002/cncr.33675.

Key clinical point: The addition of venetoclax to standard treatment regimens (VEN-based) did not improve clinical outcomes in patients with TP53-mutated acute myeloid leukemia (AML), highlighting the need for novel therapies in this patient population.

Major finding: Overall, no significant differences were observed in the rates of composite complete remission (P = .18), overall survival (median, 5.7 months vs 6.6 months; P = .4), relapse-free survival (median, 3.5 months vs 4.7 months; P = .43), 4-week mortality (7% vs 10%; P = .5), and 8-week mortality (22% vs 17%; P = .4) in patients receiving VEN-based vs non-VEN-based therapies.

Study details: Findings are from a retrospective analysis of 238 patients with newly diagnosed TP53-mutated AML treated with either VEN-based (n=58) or non-VEN-based (n=180) therapies.

Disclosures: This study was supported partly by the University of Texas MD Anderson Cancer Center Support Grant from the National Cancer Institute. Some investigators reported ties with various pharmaceutical companies.

Source: Venugopal S et al. Cancer. 2021 Jun 28. doi: 10.1002/cncr.33675.

Key clinical point: The addition of venetoclax to standard treatment regimens (VEN-based) did not improve clinical outcomes in patients with TP53-mutated acute myeloid leukemia (AML), highlighting the need for novel therapies in this patient population.

Major finding: Overall, no significant differences were observed in the rates of composite complete remission (P = .18), overall survival (median, 5.7 months vs 6.6 months; P = .4), relapse-free survival (median, 3.5 months vs 4.7 months; P = .43), 4-week mortality (7% vs 10%; P = .5), and 8-week mortality (22% vs 17%; P = .4) in patients receiving VEN-based vs non-VEN-based therapies.

Study details: Findings are from a retrospective analysis of 238 patients with newly diagnosed TP53-mutated AML treated with either VEN-based (n=58) or non-VEN-based (n=180) therapies.

Disclosures: This study was supported partly by the University of Texas MD Anderson Cancer Center Support Grant from the National Cancer Institute. Some investigators reported ties with various pharmaceutical companies.

Source: Venugopal S et al. Cancer. 2021 Jun 28. doi: 10.1002/cncr.33675.

Key clinical point: Twice-weekly surveillance with galactomannan enzyme immunoassay (GM-EIA) and b-D-glucan (BDG) assay was ineffective at detecting invasive fungal diseases (IFDs) in children, adolescents, and young adults with acute myeloid leukemia (AML) receiving antifungal prophylaxis.

Major finding: The negative predictive value was greater than 99% for an individual or combination of GM-EIA and BDG assays. However, true positive results were not observed in any sample collected within 7 days of an invasive aspergillosis/candidiasis diagnosis, resulting in sensitivity and positive predictive value for each test of 0%.

Study details: This observational study imbedded within a phase 3 Children’s Oncology Group trial (ACCL0933) included 471 patients with AML (age, 3 months-30 years) receiving fluconazole (n=235) or caspofungin (n=236).

Disclosures: This study was supported by the National Cancer Institute’s (NCI) Biomarker, Imaging and Quality of Life Studies Funding Program, and the NCI support of the Children’s Oncology Group. Some investigators including the lead author reported ties with various pharmaceutical companies.

Source: Fisher BT et al. J Pediatric Infect Dis Soc. 2021 Jun 26. doi: 10.1093/jpids/piab036.

Key clinical point: Twice-weekly surveillance with galactomannan enzyme immunoassay (GM-EIA) and b-D-glucan (BDG) assay was ineffective at detecting invasive fungal diseases (IFDs) in children, adolescents, and young adults with acute myeloid leukemia (AML) receiving antifungal prophylaxis.

Major finding: The negative predictive value was greater than 99% for an individual or combination of GM-EIA and BDG assays. However, true positive results were not observed in any sample collected within 7 days of an invasive aspergillosis/candidiasis diagnosis, resulting in sensitivity and positive predictive value for each test of 0%.

Study details: This observational study imbedded within a phase 3 Children’s Oncology Group trial (ACCL0933) included 471 patients with AML (age, 3 months-30 years) receiving fluconazole (n=235) or caspofungin (n=236).

Disclosures: This study was supported by the National Cancer Institute’s (NCI) Biomarker, Imaging and Quality of Life Studies Funding Program, and the NCI support of the Children’s Oncology Group. Some investigators including the lead author reported ties with various pharmaceutical companies.

Source: Fisher BT et al. J Pediatric Infect Dis Soc. 2021 Jun 26. doi: 10.1093/jpids/piab036.

Key clinical point: Twice-weekly surveillance with galactomannan enzyme immunoassay (GM-EIA) and b-D-glucan (BDG) assay was ineffective at detecting invasive fungal diseases (IFDs) in children, adolescents, and young adults with acute myeloid leukemia (AML) receiving antifungal prophylaxis.

Major finding: The negative predictive value was greater than 99% for an individual or combination of GM-EIA and BDG assays. However, true positive results were not observed in any sample collected within 7 days of an invasive aspergillosis/candidiasis diagnosis, resulting in sensitivity and positive predictive value for each test of 0%.

Study details: This observational study imbedded within a phase 3 Children’s Oncology Group trial (ACCL0933) included 471 patients with AML (age, 3 months-30 years) receiving fluconazole (n=235) or caspofungin (n=236).

Disclosures: This study was supported by the National Cancer Institute’s (NCI) Biomarker, Imaging and Quality of Life Studies Funding Program, and the NCI support of the Children’s Oncology Group. Some investigators including the lead author reported ties with various pharmaceutical companies.

Source: Fisher BT et al. J Pediatric Infect Dis Soc. 2021 Jun 26. doi: 10.1093/jpids/piab036.

Key clinical point: Among patients with acute myeloid leukemia (AML) with CBFB-MYH11 who underwent allogeneic or autologous hematopoietic stem cell transplantation (HSCT) in remission, D816V KIT mutation, and peri-transplant CBFB-MYH11 measurable residual disease (MRD) monitoring were associated with posttransplant relapse and survival.

Major finding: Patients with D816V KIT mutation had an increased cumulative incidence of relapse (CIR; P less than .001) and worse disease-free survival (P = .002) vs patients with other or no KIT mutations. The presence of MRD defined by 2.0 log reduction before and 3 months post-HSCT were associated with increased CIR and poorer overall survival (all P less than .001).

Study details: Findings are from a retrospective analysis of 88 patients with AML with CBFB-MYH11 who underwent HSCT in the first (n=81) or second (n=7) complete remission.

Disclosures: This study was supported by the National Research Foundation of Korea, funded by the Ministry of Education and the National R&D Program for Cancer Control, Ministry for Health and Welfare, Republic of Korea. The authors declared no conflicts of interest.

Source: Cho BS et al. Bone Marrow Transplant. 2021 Jun 28. doi: 10.1038/s41409-021-01384-w.

Key clinical point: Among patients with acute myeloid leukemia (AML) with CBFB-MYH11 who underwent allogeneic or autologous hematopoietic stem cell transplantation (HSCT) in remission, D816V KIT mutation, and peri-transplant CBFB-MYH11 measurable residual disease (MRD) monitoring were associated with posttransplant relapse and survival.

Major finding: Patients with D816V KIT mutation had an increased cumulative incidence of relapse (CIR; P less than .001) and worse disease-free survival (P = .002) vs patients with other or no KIT mutations. The presence of MRD defined by 2.0 log reduction before and 3 months post-HSCT were associated with increased CIR and poorer overall survival (all P less than .001).

Study details: Findings are from a retrospective analysis of 88 patients with AML with CBFB-MYH11 who underwent HSCT in the first (n=81) or second (n=7) complete remission.

Disclosures: This study was supported by the National Research Foundation of Korea, funded by the Ministry of Education and the National R&D Program for Cancer Control, Ministry for Health and Welfare, Republic of Korea. The authors declared no conflicts of interest.

Source: Cho BS et al. Bone Marrow Transplant. 2021 Jun 28. doi: 10.1038/s41409-021-01384-w.

Key clinical point: Among patients with acute myeloid leukemia (AML) with CBFB-MYH11 who underwent allogeneic or autologous hematopoietic stem cell transplantation (HSCT) in remission, D816V KIT mutation, and peri-transplant CBFB-MYH11 measurable residual disease (MRD) monitoring were associated with posttransplant relapse and survival.

Major finding: Patients with D816V KIT mutation had an increased cumulative incidence of relapse (CIR; P less than .001) and worse disease-free survival (P = .002) vs patients with other or no KIT mutations. The presence of MRD defined by 2.0 log reduction before and 3 months post-HSCT were associated with increased CIR and poorer overall survival (all P less than .001).

Study details: Findings are from a retrospective analysis of 88 patients with AML with CBFB-MYH11 who underwent HSCT in the first (n=81) or second (n=7) complete remission.

Disclosures: This study was supported by the National Research Foundation of Korea, funded by the Ministry of Education and the National R&D Program for Cancer Control, Ministry for Health and Welfare, Republic of Korea. The authors declared no conflicts of interest.

Source: Cho BS et al. Bone Marrow Transplant. 2021 Jun 28. doi: 10.1038/s41409-021-01384-w.

Key clinical point: Female vs male gender confers a survival advantage in patients with nonacute promyelocytic leukemia (APL) acute myeloid leukemia (AML). However, reasons for this sex-specific advantage remain to be explored.

Major finding: Among patients with non-APL AML, females vs males had a significantly longer overall survival (hazard ratio, 0.85; P = .0001), but not disease-free survival (P = .14). This survival advantage was irrespective of patient age, white blood cell count, or initial blood and marrow blast counts.

Study details: Findings are from a retrospective analysis of 3,546 newly diagnosed patients with AML, including 548 with APL enrolled in 10 studies of the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group between March 1984 and November 2008.

Disclosures: This study was supported by the National Cancer Institute of the National Institutes of Health. The authors declared no conflicts of interest.

Source: Wiernik PH et al. Br J Haematol. 2021 Jun 17. doi: 10.1111/bjh.17523.

Key clinical point: Female vs male gender confers a survival advantage in patients with nonacute promyelocytic leukemia (APL) acute myeloid leukemia (AML). However, reasons for this sex-specific advantage remain to be explored.

Major finding: Among patients with non-APL AML, females vs males had a significantly longer overall survival (hazard ratio, 0.85; P = .0001), but not disease-free survival (P = .14). This survival advantage was irrespective of patient age, white blood cell count, or initial blood and marrow blast counts.

Study details: Findings are from a retrospective analysis of 3,546 newly diagnosed patients with AML, including 548 with APL enrolled in 10 studies of the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group between March 1984 and November 2008.

Disclosures: This study was supported by the National Cancer Institute of the National Institutes of Health. The authors declared no conflicts of interest.

Source: Wiernik PH et al. Br J Haematol. 2021 Jun 17. doi: 10.1111/bjh.17523.

Key clinical point: Female vs male gender confers a survival advantage in patients with nonacute promyelocytic leukemia (APL) acute myeloid leukemia (AML). However, reasons for this sex-specific advantage remain to be explored.

Major finding: Among patients with non-APL AML, females vs males had a significantly longer overall survival (hazard ratio, 0.85; P = .0001), but not disease-free survival (P = .14). This survival advantage was irrespective of patient age, white blood cell count, or initial blood and marrow blast counts.

Study details: Findings are from a retrospective analysis of 3,546 newly diagnosed patients with AML, including 548 with APL enrolled in 10 studies of the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group between March 1984 and November 2008.

Disclosures: This study was supported by the National Cancer Institute of the National Institutes of Health. The authors declared no conflicts of interest.

Source: Wiernik PH et al. Br J Haematol. 2021 Jun 17. doi: 10.1111/bjh.17523.