AML

Key clinical point: Alvocidib followed by cytarabine and mitoxantrone (ACM) was clinically active and well tolerated in patients with myeloid cell leukemia-1 (MCL-1)-dependent relapsed/refractory (R/R) acute myeloid leukemia (AML).

Major finding: The rates of composite complete remission after 1 cycle of ACM therapy were 47%, 21%, 64%, and 52% in patients with R/R AML with MCL-1 <15%, 15% to <30%, 30% to <40%, and ≥40%, respectively. The rate of 30-day mortality was 6% in the R/R AML cohort.

Study details: Findings are from the phase 2 Zella-201 study including 221 adult patients with R/R AML and an exploratory cohort of 169 patients with newly diagnosed high-risk AML, of which 39% were MCL-1 dependent (≥40%).

Disclosures: This study was supported by Tolero Pharmaceuticals, acquired by Sumitomo Dainippon Pharma (SDP). Some investigators, including the lead author, reported being employees of; receiving research funding, honoraria, grants, or drug support from; being on advisory boards or data monitoring committees for; or receiving consultancy or speaker roles from various sources, including Tolero and SDP.

Source: Zeidner JF et al. Blood Cancer J. 2021;11:175 (Oct 30). Doi: 10.1038/s41408-021-00568-3.

Key clinical point: Alvocidib followed by cytarabine and mitoxantrone (ACM) was clinically active and well tolerated in patients with myeloid cell leukemia-1 (MCL-1)-dependent relapsed/refractory (R/R) acute myeloid leukemia (AML).

Major finding: The rates of composite complete remission after 1 cycle of ACM therapy were 47%, 21%, 64%, and 52% in patients with R/R AML with MCL-1 <15%, 15% to <30%, 30% to <40%, and ≥40%, respectively. The rate of 30-day mortality was 6% in the R/R AML cohort.

Study details: Findings are from the phase 2 Zella-201 study including 221 adult patients with R/R AML and an exploratory cohort of 169 patients with newly diagnosed high-risk AML, of which 39% were MCL-1 dependent (≥40%).

Disclosures: This study was supported by Tolero Pharmaceuticals, acquired by Sumitomo Dainippon Pharma (SDP). Some investigators, including the lead author, reported being employees of; receiving research funding, honoraria, grants, or drug support from; being on advisory boards or data monitoring committees for; or receiving consultancy or speaker roles from various sources, including Tolero and SDP.

Source: Zeidner JF et al. Blood Cancer J. 2021;11:175 (Oct 30). Doi: 10.1038/s41408-021-00568-3.

Key clinical point: Alvocidib followed by cytarabine and mitoxantrone (ACM) was clinically active and well tolerated in patients with myeloid cell leukemia-1 (MCL-1)-dependent relapsed/refractory (R/R) acute myeloid leukemia (AML).

Major finding: The rates of composite complete remission after 1 cycle of ACM therapy were 47%, 21%, 64%, and 52% in patients with R/R AML with MCL-1 <15%, 15% to <30%, 30% to <40%, and ≥40%, respectively. The rate of 30-day mortality was 6% in the R/R AML cohort.

Study details: Findings are from the phase 2 Zella-201 study including 221 adult patients with R/R AML and an exploratory cohort of 169 patients with newly diagnosed high-risk AML, of which 39% were MCL-1 dependent (≥40%).

Disclosures: This study was supported by Tolero Pharmaceuticals, acquired by Sumitomo Dainippon Pharma (SDP). Some investigators, including the lead author, reported being employees of; receiving research funding, honoraria, grants, or drug support from; being on advisory boards or data monitoring committees for; or receiving consultancy or speaker roles from various sources, including Tolero and SDP.

Source: Zeidner JF et al. Blood Cancer J. 2021;11:175 (Oct 30). Doi: 10.1038/s41408-021-00568-3.

Key clinical point: Intracranial hemorrhage (ICH) is still a deadly complication affecting survival in patients with newly diagnosed nonacute promyelocytic acute myeloid leukemia (AML) receiving intensive induction chemotherapy (IIC) despite routine prophylactic platelet substitution.

Major finding: Overall, 4% of patients developed ICH. Patients with ICH vs. without had worse overall survival (median, 20.1 vs. 104.8 months; P = .0079) with female sex (adjusted odds ratio [aOR] 3.79; P = .03), low thrombocyte (aOR 1.2; P = .03), and fibrinogen levels at admission (aOR 1.62; P = .03) being risk factors for ICH.

Study details: This retrospective study included 423 patients with newly diagnosed nonacute promyelocytic AML hospitalized for IIC with routine platelet transfusions at <10 thrombocytes/nL.

Disclosures: This study did not receive any funding. The authors declared no conflict of interests.

Source: Koschade SE et al. Eur J Haematol. 2021(Oct 29). Doi: 10.1111/ejh.13718.

Key clinical point: Intracranial hemorrhage (ICH) is still a deadly complication affecting survival in patients with newly diagnosed nonacute promyelocytic acute myeloid leukemia (AML) receiving intensive induction chemotherapy (IIC) despite routine prophylactic platelet substitution.

Major finding: Overall, 4% of patients developed ICH. Patients with ICH vs. without had worse overall survival (median, 20.1 vs. 104.8 months; P = .0079) with female sex (adjusted odds ratio [aOR] 3.79; P = .03), low thrombocyte (aOR 1.2; P = .03), and fibrinogen levels at admission (aOR 1.62; P = .03) being risk factors for ICH.

Study details: This retrospective study included 423 patients with newly diagnosed nonacute promyelocytic AML hospitalized for IIC with routine platelet transfusions at <10 thrombocytes/nL.

Disclosures: This study did not receive any funding. The authors declared no conflict of interests.

Source: Koschade SE et al. Eur J Haematol. 2021(Oct 29). Doi: 10.1111/ejh.13718.

Key clinical point: Intracranial hemorrhage (ICH) is still a deadly complication affecting survival in patients with newly diagnosed nonacute promyelocytic acute myeloid leukemia (AML) receiving intensive induction chemotherapy (IIC) despite routine prophylactic platelet substitution.

Major finding: Overall, 4% of patients developed ICH. Patients with ICH vs. without had worse overall survival (median, 20.1 vs. 104.8 months; P = .0079) with female sex (adjusted odds ratio [aOR] 3.79; P = .03), low thrombocyte (aOR 1.2; P = .03), and fibrinogen levels at admission (aOR 1.62; P = .03) being risk factors for ICH.

Study details: This retrospective study included 423 patients with newly diagnosed nonacute promyelocytic AML hospitalized for IIC with routine platelet transfusions at <10 thrombocytes/nL.

Disclosures: This study did not receive any funding. The authors declared no conflict of interests.

Source: Koschade SE et al. Eur J Haematol. 2021(Oct 29). Doi: 10.1111/ejh.13718.

Key clinical point: Antimicrobial prophylaxis significantly reduced rates of bloodstream infection (BSI), invasive fungal infection (IFI), and febrile neutropenia (FN) in pediatric patients with acute myeloid leukemia (AML) receiving chemotherapy.

Major finding: Episodes of BSI (Gram-negative: 5% vs. 12%, P = .002; Gram-positive: 1% vs. 5%; P = .024) and IFI (0% vs. 4%; P = .003) decreased significantly in the prophylaxis vs. preprophylaxis period. FN episodes during induction (78% vs. 99%) and high-dose (64% vs. 94%) or moderate-dose (27% vs. 58%) chemotherapy also reduced in prophylaxis vs. preprophylaxis period (all P < .001).

Study details: This observational study included 90 children with newly diagnosed AML receiving induction and postremission high- or moderate-dose chemotherapy. Antimicrobial prophylaxis administered in 28 patients consisted of ciprofloxacin, voriconazole, and vancomycin.

Disclosures: No source of funding was identified. The authors declared no conflict of interests.

Source: Yeh TC et al. Sci Rep. 2021;11: 21142 (Oct 27). Doi: 10.1038/s41598-021-00725-5.

Key clinical point: Antimicrobial prophylaxis significantly reduced rates of bloodstream infection (BSI), invasive fungal infection (IFI), and febrile neutropenia (FN) in pediatric patients with acute myeloid leukemia (AML) receiving chemotherapy.

Major finding: Episodes of BSI (Gram-negative: 5% vs. 12%, P = .002; Gram-positive: 1% vs. 5%; P = .024) and IFI (0% vs. 4%; P = .003) decreased significantly in the prophylaxis vs. preprophylaxis period. FN episodes during induction (78% vs. 99%) and high-dose (64% vs. 94%) or moderate-dose (27% vs. 58%) chemotherapy also reduced in prophylaxis vs. preprophylaxis period (all P < .001).

Study details: This observational study included 90 children with newly diagnosed AML receiving induction and postremission high- or moderate-dose chemotherapy. Antimicrobial prophylaxis administered in 28 patients consisted of ciprofloxacin, voriconazole, and vancomycin.

Disclosures: No source of funding was identified. The authors declared no conflict of interests.

Source: Yeh TC et al. Sci Rep. 2021;11: 21142 (Oct 27). Doi: 10.1038/s41598-021-00725-5.

Key clinical point: Antimicrobial prophylaxis significantly reduced rates of bloodstream infection (BSI), invasive fungal infection (IFI), and febrile neutropenia (FN) in pediatric patients with acute myeloid leukemia (AML) receiving chemotherapy.

Major finding: Episodes of BSI (Gram-negative: 5% vs. 12%, P = .002; Gram-positive: 1% vs. 5%; P = .024) and IFI (0% vs. 4%; P = .003) decreased significantly in the prophylaxis vs. preprophylaxis period. FN episodes during induction (78% vs. 99%) and high-dose (64% vs. 94%) or moderate-dose (27% vs. 58%) chemotherapy also reduced in prophylaxis vs. preprophylaxis period (all P < .001).

Study details: This observational study included 90 children with newly diagnosed AML receiving induction and postremission high- or moderate-dose chemotherapy. Antimicrobial prophylaxis administered in 28 patients consisted of ciprofloxacin, voriconazole, and vancomycin.

Disclosures: No source of funding was identified. The authors declared no conflict of interests.

Source: Yeh TC et al. Sci Rep. 2021;11: 21142 (Oct 27). Doi: 10.1038/s41598-021-00725-5.

Key clinical point: Wilms’ tumor 1 helper peptide OCV-501 was well tolerated, but did not significantly improve clinical outcomes in elderly patients with acute myeloid leukemia (AML) in first complete remission (CR1). However, immune responders may benefit from OCV-501.

Major finding: The median disease-free survival (P = .7671) and overall survival (P = .8540) were not significantly different between OCV-501 vs. placebo groups. However, those with an immune response to OCV-501 had better survival outcomes (P < .0001). Adverse drug reactions were more frequent in patients receiving OCV-501 vs. placebo (91.2% vs. 58.5%) and were mainly injection-site reactions.

Study details: This phase 2 study included 134 elderly (age ³60 years) patients with AML who achieved CR1 within 1 or 2 courses of standard induction therapies and were randomly assigned to either OCV-501 (n = 69) or placebo (n = 65).

Disclosures: This study was funded by Otsuka Pharmaceutical Co., Ltd (OPCL). K Masui, Y Ihara, M Hirota, and N Shimofurutani reported being employees of OPCL. Some investigators, including the lead author, reported receiving grants and personal fees from various sources including OPCL.

Source: Kiguchi T et al. Cancer Immunol Immunother. 2021(Oct 22). Doi: 10.1007/s00262-021-03074-4.

Key clinical point: Wilms’ tumor 1 helper peptide OCV-501 was well tolerated, but did not significantly improve clinical outcomes in elderly patients with acute myeloid leukemia (AML) in first complete remission (CR1). However, immune responders may benefit from OCV-501.

Major finding: The median disease-free survival (P = .7671) and overall survival (P = .8540) were not significantly different between OCV-501 vs. placebo groups. However, those with an immune response to OCV-501 had better survival outcomes (P < .0001). Adverse drug reactions were more frequent in patients receiving OCV-501 vs. placebo (91.2% vs. 58.5%) and were mainly injection-site reactions.

Study details: This phase 2 study included 134 elderly (age ³60 years) patients with AML who achieved CR1 within 1 or 2 courses of standard induction therapies and were randomly assigned to either OCV-501 (n = 69) or placebo (n = 65).

Disclosures: This study was funded by Otsuka Pharmaceutical Co., Ltd (OPCL). K Masui, Y Ihara, M Hirota, and N Shimofurutani reported being employees of OPCL. Some investigators, including the lead author, reported receiving grants and personal fees from various sources including OPCL.

Source: Kiguchi T et al. Cancer Immunol Immunother. 2021(Oct 22). Doi: 10.1007/s00262-021-03074-4.

Key clinical point: Wilms’ tumor 1 helper peptide OCV-501 was well tolerated, but did not significantly improve clinical outcomes in elderly patients with acute myeloid leukemia (AML) in first complete remission (CR1). However, immune responders may benefit from OCV-501.

Major finding: The median disease-free survival (P = .7671) and overall survival (P = .8540) were not significantly different between OCV-501 vs. placebo groups. However, those with an immune response to OCV-501 had better survival outcomes (P < .0001). Adverse drug reactions were more frequent in patients receiving OCV-501 vs. placebo (91.2% vs. 58.5%) and were mainly injection-site reactions.

Study details: This phase 2 study included 134 elderly (age ³60 years) patients with AML who achieved CR1 within 1 or 2 courses of standard induction therapies and were randomly assigned to either OCV-501 (n = 69) or placebo (n = 65).

Disclosures: This study was funded by Otsuka Pharmaceutical Co., Ltd (OPCL). K Masui, Y Ihara, M Hirota, and N Shimofurutani reported being employees of OPCL. Some investigators, including the lead author, reported receiving grants and personal fees from various sources including OPCL.

Source: Kiguchi T et al. Cancer Immunol Immunother. 2021(Oct 22). Doi: 10.1007/s00262-021-03074-4.

Key clinical point: Optimization of a traditional induction regimen with idarubicin and cytarabine (IA) with additional homoharringtonine according to day 5 peripheral blast clearance rate (D5-PBCR) ³99.55% (D5-PBCR−) is feasible in patients with newly diagnosed acute myeloid leukemia (AML) with reversal of unfavorable outcomes observed in patients with D5-PBCR <99.55% (D5-PBCR+).

Major finding: Rates of composite complete remission after 1 cycle of induction (CR1) were 87.5% and 80.0% in D5-PBCR− and D5-PBCR+ groups, respectively, with CR1 rate improving by almost 18% in the D5-PBCR+ group compared with the historical data (P = .049). The median overall survival, event-free survival, and grade 3 or higher adverse events were similar between the 2 groups.

Study details: Findings are from a phase 2 RJ-AML 2014 trial including 151 adult patients with untreated newly diagnosed AML who received a dose-reduced IA induction regimen. Patients with D5-PBCR+ (n = 65) received IA+homoharringtonine.

Disclosures: This study was supported by the Shanghai Jiao Tong University School of Medicine Multi-Center Clinical Research Project Grant and the National Natural Science Foundation of China. The authors declared no conflict of interests.

Source: Zhang Y et al. Am J Hematol. 2021(Oct 23). Doi: 10.1002/ajh.26386.

Key clinical point: Optimization of a traditional induction regimen with idarubicin and cytarabine (IA) with additional homoharringtonine according to day 5 peripheral blast clearance rate (D5-PBCR) ³99.55% (D5-PBCR−) is feasible in patients with newly diagnosed acute myeloid leukemia (AML) with reversal of unfavorable outcomes observed in patients with D5-PBCR <99.55% (D5-PBCR+).

Major finding: Rates of composite complete remission after 1 cycle of induction (CR1) were 87.5% and 80.0% in D5-PBCR− and D5-PBCR+ groups, respectively, with CR1 rate improving by almost 18% in the D5-PBCR+ group compared with the historical data (P = .049). The median overall survival, event-free survival, and grade 3 or higher adverse events were similar between the 2 groups.

Study details: Findings are from a phase 2 RJ-AML 2014 trial including 151 adult patients with untreated newly diagnosed AML who received a dose-reduced IA induction regimen. Patients with D5-PBCR+ (n = 65) received IA+homoharringtonine.

Disclosures: This study was supported by the Shanghai Jiao Tong University School of Medicine Multi-Center Clinical Research Project Grant and the National Natural Science Foundation of China. The authors declared no conflict of interests.

Source: Zhang Y et al. Am J Hematol. 2021(Oct 23). Doi: 10.1002/ajh.26386.

Key clinical point: Optimization of a traditional induction regimen with idarubicin and cytarabine (IA) with additional homoharringtonine according to day 5 peripheral blast clearance rate (D5-PBCR) ³99.55% (D5-PBCR−) is feasible in patients with newly diagnosed acute myeloid leukemia (AML) with reversal of unfavorable outcomes observed in patients with D5-PBCR <99.55% (D5-PBCR+).

Major finding: Rates of composite complete remission after 1 cycle of induction (CR1) were 87.5% and 80.0% in D5-PBCR− and D5-PBCR+ groups, respectively, with CR1 rate improving by almost 18% in the D5-PBCR+ group compared with the historical data (P = .049). The median overall survival, event-free survival, and grade 3 or higher adverse events were similar between the 2 groups.

Study details: Findings are from a phase 2 RJ-AML 2014 trial including 151 adult patients with untreated newly diagnosed AML who received a dose-reduced IA induction regimen. Patients with D5-PBCR+ (n = 65) received IA+homoharringtonine.

Disclosures: This study was supported by the Shanghai Jiao Tong University School of Medicine Multi-Center Clinical Research Project Grant and the National Natural Science Foundation of China. The authors declared no conflict of interests.

Source: Zhang Y et al. Am J Hematol. 2021(Oct 23). Doi: 10.1002/ajh.26386.

Key clinical point: Reduced intensity conditioning (RIC) transplant in first remission vs. chemotherapy alone improved survival in older patients with acute myeloid leukemia (AML) who lacked favorable risk cytogenetics and were considered fit for intensive treatment.

Major finding: During a median follow-up of 60 months from remission, patients receiving RIC transplant vs. no transplant had superior survival (37% vs. 20%; hazard ratio [HR] 0.67; P < .001). Survival benefit with transplant in first remission vs. chemotherapy alone was observed across all Wheatley risk groups (adjusted HR 0.68; P < .001).

Study details: Findings are from the NCRI AML16 trial including 932 patients (age 60-70 years) with AML who entered remission and lacked favorable risk. Of these, 144 underwent RIC transplants from either matched sibling donors (n = 52) or matched unrelated donors (n = 92).

Disclosures: This NCRI AML16 trial was supported by Cancer Research UK. The authors declared no conflict of interests.

Source: Russell NH et al. Haematologica. 2021(Oct 14). Doi: 10.3324/haematol.2021.279010.

Key clinical point: Reduced intensity conditioning (RIC) transplant in first remission vs. chemotherapy alone improved survival in older patients with acute myeloid leukemia (AML) who lacked favorable risk cytogenetics and were considered fit for intensive treatment.

Major finding: During a median follow-up of 60 months from remission, patients receiving RIC transplant vs. no transplant had superior survival (37% vs. 20%; hazard ratio [HR] 0.67; P < .001). Survival benefit with transplant in first remission vs. chemotherapy alone was observed across all Wheatley risk groups (adjusted HR 0.68; P < .001).

Study details: Findings are from the NCRI AML16 trial including 932 patients (age 60-70 years) with AML who entered remission and lacked favorable risk. Of these, 144 underwent RIC transplants from either matched sibling donors (n = 52) or matched unrelated donors (n = 92).

Disclosures: This NCRI AML16 trial was supported by Cancer Research UK. The authors declared no conflict of interests.

Source: Russell NH et al. Haematologica. 2021(Oct 14). Doi: 10.3324/haematol.2021.279010.

Key clinical point: Reduced intensity conditioning (RIC) transplant in first remission vs. chemotherapy alone improved survival in older patients with acute myeloid leukemia (AML) who lacked favorable risk cytogenetics and were considered fit for intensive treatment.

Major finding: During a median follow-up of 60 months from remission, patients receiving RIC transplant vs. no transplant had superior survival (37% vs. 20%; hazard ratio [HR] 0.67; P < .001). Survival benefit with transplant in first remission vs. chemotherapy alone was observed across all Wheatley risk groups (adjusted HR 0.68; P < .001).

Study details: Findings are from the NCRI AML16 trial including 932 patients (age 60-70 years) with AML who entered remission and lacked favorable risk. Of these, 144 underwent RIC transplants from either matched sibling donors (n = 52) or matched unrelated donors (n = 92).

Disclosures: This NCRI AML16 trial was supported by Cancer Research UK. The authors declared no conflict of interests.

Source: Russell NH et al. Haematologica. 2021(Oct 14). Doi: 10.3324/haematol.2021.279010.

Key clinical point: In patients with acute myeloid leukemia (AML), short-term posttransplant outcomes seemed similar in those who achieved first complete remission (CR1) with either first-line therapy with 5-azacitidine combined with venetoclax (aza-ven) or traditional intensive chemotherapy (IC).

Major finding: Rates of 12-month relapse-free survival and overall survival in aza-ven vs. IC groups were 58% vs. 54% and 63.2% vs. 70.8%, respectively. Cumulative incidences of acute graft versus host disease (GVHD) at 6 months and chronic GVHD at 12 months were 58% and 40% in the aza-ven group and 62% and 42% in the IC group, respectively.

Study details: This retrospective study included patients with AML who underwent allogeneic hematopoietic cell transplantation after achieving CR1 with either first-line aza-ven therapy (n = 24) or IC (n = 24).

Disclosures: No source of funding was identified. The authors declared no conflict of interests.

Source: Pasvolsky O et al. Ann Hematol. 2021(Oct 9). Doi: 10.1007/s00277-021-04693-8.

Key clinical point: In patients with acute myeloid leukemia (AML), short-term posttransplant outcomes seemed similar in those who achieved first complete remission (CR1) with either first-line therapy with 5-azacitidine combined with venetoclax (aza-ven) or traditional intensive chemotherapy (IC).

Major finding: Rates of 12-month relapse-free survival and overall survival in aza-ven vs. IC groups were 58% vs. 54% and 63.2% vs. 70.8%, respectively. Cumulative incidences of acute graft versus host disease (GVHD) at 6 months and chronic GVHD at 12 months were 58% and 40% in the aza-ven group and 62% and 42% in the IC group, respectively.

Study details: This retrospective study included patients with AML who underwent allogeneic hematopoietic cell transplantation after achieving CR1 with either first-line aza-ven therapy (n = 24) or IC (n = 24).

Disclosures: No source of funding was identified. The authors declared no conflict of interests.

Source: Pasvolsky O et al. Ann Hematol. 2021(Oct 9). Doi: 10.1007/s00277-021-04693-8.

Key clinical point: In patients with acute myeloid leukemia (AML), short-term posttransplant outcomes seemed similar in those who achieved first complete remission (CR1) with either first-line therapy with 5-azacitidine combined with venetoclax (aza-ven) or traditional intensive chemotherapy (IC).

Major finding: Rates of 12-month relapse-free survival and overall survival in aza-ven vs. IC groups were 58% vs. 54% and 63.2% vs. 70.8%, respectively. Cumulative incidences of acute graft versus host disease (GVHD) at 6 months and chronic GVHD at 12 months were 58% and 40% in the aza-ven group and 62% and 42% in the IC group, respectively.

Study details: This retrospective study included patients with AML who underwent allogeneic hematopoietic cell transplantation after achieving CR1 with either first-line aza-ven therapy (n = 24) or IC (n = 24).

Disclosures: No source of funding was identified. The authors declared no conflict of interests.

Source: Pasvolsky O et al. Ann Hematol. 2021(Oct 9). Doi: 10.1007/s00277-021-04693-8.

Key clinical point: Outpatient vs. inpatient neutropenia management after chemotherapy was not associated with an increased bacteremia incidence, treatment delays, or worse health-related quality of life (HRQoL) in pediatric patients with acute myeloid leukemia (AML).

Major finding: Bacteremia incidence (adjusted risk ratio 0.73; P = .08), mean time to next chemotherapy course (intensification I: adjusted mean difference [D] −1.0; P = .51; intensification II: D −1.5; P = .79), and HRQoL (Pediatric Quality of Life Inventory Generic Core Scales total score: D −2.8; P = .56) were not significantly different with outpatient vs. inpatient neutropenia management.

Study details: This cohort study included 554 pediatric patients with AML who received frontline chemotherapy with either outpatient or inpatient neutropenia management.

Disclosures: This study was supported by Patient-Centered Outcomes Research Institute (PCORI) and partly by an award from the US National Heart, Lung, and Blood Institute (NHLBI) to KD Getz. Some investigators, including the lead author, reported receiving grants and personal fees and being a member of the data safety monitoring board for various sources including PCORI and NHLBI.

Source: Getz KD et al. JAMA Netw Open. 2021(Oct 28). Doi: 10.1001/jamanetworkopen.2021.28385.

Key clinical point: Outpatient vs. inpatient neutropenia management after chemotherapy was not associated with an increased bacteremia incidence, treatment delays, or worse health-related quality of life (HRQoL) in pediatric patients with acute myeloid leukemia (AML).

Major finding: Bacteremia incidence (adjusted risk ratio 0.73; P = .08), mean time to next chemotherapy course (intensification I: adjusted mean difference [D] −1.0; P = .51; intensification II: D −1.5; P = .79), and HRQoL (Pediatric Quality of Life Inventory Generic Core Scales total score: D −2.8; P = .56) were not significantly different with outpatient vs. inpatient neutropenia management.

Study details: This cohort study included 554 pediatric patients with AML who received frontline chemotherapy with either outpatient or inpatient neutropenia management.

Disclosures: This study was supported by Patient-Centered Outcomes Research Institute (PCORI) and partly by an award from the US National Heart, Lung, and Blood Institute (NHLBI) to KD Getz. Some investigators, including the lead author, reported receiving grants and personal fees and being a member of the data safety monitoring board for various sources including PCORI and NHLBI.

Source: Getz KD et al. JAMA Netw Open. 2021(Oct 28). Doi: 10.1001/jamanetworkopen.2021.28385.

Key clinical point: Outpatient vs. inpatient neutropenia management after chemotherapy was not associated with an increased bacteremia incidence, treatment delays, or worse health-related quality of life (HRQoL) in pediatric patients with acute myeloid leukemia (AML).

Major finding: Bacteremia incidence (adjusted risk ratio 0.73; P = .08), mean time to next chemotherapy course (intensification I: adjusted mean difference [D] −1.0; P = .51; intensification II: D −1.5; P = .79), and HRQoL (Pediatric Quality of Life Inventory Generic Core Scales total score: D −2.8; P = .56) were not significantly different with outpatient vs. inpatient neutropenia management.

Study details: This cohort study included 554 pediatric patients with AML who received frontline chemotherapy with either outpatient or inpatient neutropenia management.

Disclosures: This study was supported by Patient-Centered Outcomes Research Institute (PCORI) and partly by an award from the US National Heart, Lung, and Blood Institute (NHLBI) to KD Getz. Some investigators, including the lead author, reported receiving grants and personal fees and being a member of the data safety monitoring board for various sources including PCORI and NHLBI.

Source: Getz KD et al. JAMA Netw Open. 2021(Oct 28). Doi: 10.1001/jamanetworkopen.2021.28385.

Key clinical point: Combination therapy with enasidenib and azacitidine (Ena-AZA) was well tolerated and had a better response rate than azacitidine alone (AZA) in patients with newly diagnosed (ND) mutant-IDH2 acute myeloid leukemia (AML) and ineligible for intensive chemotherapy (IC).

Major finding: The overall response rate was significantly higher in patients receiving Ena-AZA vs. AZA (74% vs. 36%; odds ratio 4.9; P = .0003). The most frequent grade 3 or 4 events in the Ena-AZA vs. AZA groups were thrombocytopenia (37% vs. 19%) and neutropenia (37% vs. 25%).

Study details: Findings are from the phase 2 AG221-AML-005 study including 101 adult patients with ND mutant-IDH2 AML who were ineligible for IC. They were randomly assigned to Ena-AZA (n = 68) or AZA (n = 33).

Disclosures: This study was funded by Celgene, a wholly owned subsidiary of Bristol Myers Squibb (BMS). MG Frattini, P Martin-Regueira, F Lersch, J Gong, and M Hasan reported employment and equity ownership in BMS/Celgene. Other authors reported receiving grants, personal fees, royalties, nonfinancial support, research funding, and honoraria from various sources, including BMS/Celgene.

Source: DiNardo CD et al. Lancet Oncol. 2021;22(11):P1597-P1608 (Oct 18). Doi: 10.1016/S1470-2045(21)00494-0.

Key clinical point: Combination therapy with enasidenib and azacitidine (Ena-AZA) was well tolerated and had a better response rate than azacitidine alone (AZA) in patients with newly diagnosed (ND) mutant-IDH2 acute myeloid leukemia (AML) and ineligible for intensive chemotherapy (IC).

Major finding: The overall response rate was significantly higher in patients receiving Ena-AZA vs. AZA (74% vs. 36%; odds ratio 4.9; P = .0003). The most frequent grade 3 or 4 events in the Ena-AZA vs. AZA groups were thrombocytopenia (37% vs. 19%) and neutropenia (37% vs. 25%).

Study details: Findings are from the phase 2 AG221-AML-005 study including 101 adult patients with ND mutant-IDH2 AML who were ineligible for IC. They were randomly assigned to Ena-AZA (n = 68) or AZA (n = 33).

Disclosures: This study was funded by Celgene, a wholly owned subsidiary of Bristol Myers Squibb (BMS). MG Frattini, P Martin-Regueira, F Lersch, J Gong, and M Hasan reported employment and equity ownership in BMS/Celgene. Other authors reported receiving grants, personal fees, royalties, nonfinancial support, research funding, and honoraria from various sources, including BMS/Celgene.

Source: DiNardo CD et al. Lancet Oncol. 2021;22(11):P1597-P1608 (Oct 18). Doi: 10.1016/S1470-2045(21)00494-0.

Key clinical point: Combination therapy with enasidenib and azacitidine (Ena-AZA) was well tolerated and had a better response rate than azacitidine alone (AZA) in patients with newly diagnosed (ND) mutant-IDH2 acute myeloid leukemia (AML) and ineligible for intensive chemotherapy (IC).

Major finding: The overall response rate was significantly higher in patients receiving Ena-AZA vs. AZA (74% vs. 36%; odds ratio 4.9; P = .0003). The most frequent grade 3 or 4 events in the Ena-AZA vs. AZA groups were thrombocytopenia (37% vs. 19%) and neutropenia (37% vs. 25%).

Study details: Findings are from the phase 2 AG221-AML-005 study including 101 adult patients with ND mutant-IDH2 AML who were ineligible for IC. They were randomly assigned to Ena-AZA (n = 68) or AZA (n = 33).

Disclosures: This study was funded by Celgene, a wholly owned subsidiary of Bristol Myers Squibb (BMS). MG Frattini, P Martin-Regueira, F Lersch, J Gong, and M Hasan reported employment and equity ownership in BMS/Celgene. Other authors reported receiving grants, personal fees, royalties, nonfinancial support, research funding, and honoraria from various sources, including BMS/Celgene.

Source: DiNardo CD et al. Lancet Oncol. 2021;22(11):P1597-P1608 (Oct 18). Doi: 10.1016/S1470-2045(21)00494-0.

A number of late-phase clinical trials in leukemia have opened in recent months. Maybe one of your patients could benefit from being enrolled.

Adults and children with acute or chronic leukemias

A phase 2 study partnering with the National Marrow Donor Program is seeking individuals aged 1-65 years with lymphoma or one of the following leukemias: “acute leukemia”, acute lymphoblastic (ALL), acute myelogenous (AML), mixed-phenotype acute, chronic myelogenous (CML), and chronic lymphocytic (CLL). Researchers hope to find a way to improve outcomes of hematopoietic-cell transplantation from mismatched, unrelated donors. Participants will receive the transplant and one of seven drug regimens and will be followed for a year. The trial plans to enroll 180 people and began recruiting on Sept. 30 in California, New York, and Virginia. The primary outcome is overall survival (OS). Quality of life (QoL) will not be measured.

Mast-cell leukemia (MCL)

Adults with MCL are sought for a phase 2 study of bezuclastinib, an experimental tyrosine-kinase inhibitor (TKI) called CGT9486. CGT9486 blocks the activity of a mutated version of tyrosine-kinase receptor KIT, called KIT D816V, which is known to cause systemic mastocytosis. Participants will receive oral CGT9486 daily for up to 18 months. The study opened in October, aiming for 140 participants with any advanced systemic mastocytoses (including MCL) at sites in California, Florida, Massachusetts, New York, Ohio, Texas, and Utah. OS and QoL will be tracked.

Previously Treated CLL/Small Lymphocytic Lymphoma (SLL)

Patients with CLL/SLL who have progressed on previous therapy can join a phase 3 study of another experimental oral TIK, pirtobrutinib, this time targeting Bruton’s tyrosine kinase (BTK). BTK plays a key role in the lifecycle of white blood cells. Participants will receive either “fixed-duration” pirtobrutinib plus venetoclax (Venclexta) and rituximab (Ruxience, Riabni, Truxima, Rituxan, MabThera) or the venetoclax-rituximab combo only, for up to 5 years. Investigators started recruiting in September, aiming for 600 participants across Florida, Louisiana, Missouri, New York, and Tennessee. Progression-free survival is the primary outcome; OS is a secondary outcome and QoL will not be tracked.

High-grade myeloid cancers with measurable residual disease

Patients with AML, myelodysplastic syndrome with excess blasts-2 or myeloid neoplasm, and whose original disease is still present, are eligible for a phase 2 study of CPX-351 (daunorubicin-cytarabine, Vyxeos). The intravenous chemotherapy was approved in 2017 for certain types of AML. The goal of this study is to determine if pretreatment with CPX-351 improves the outcome of donor stem-cell transplantation. Patients will either undergo immediate transplantation or receive CPX-351 for up to 10 days followed 60 days later by the transplant. The study, being conducted at the Fred Hutchinson Cancer Research Center in Seattle, started recruiting 130 patients in August. The primary outcome is OS; QoL will not be tracked.

Newly diagnosed Philadelphia-negative ALL

Patients aged 22 or older with Philadelphia-negative ALL who have not received chemotherapy or radiation therapy are invited to join a trial of calaspargase pegol (Asparlas). The therapy was approved in 2018 for ALL in children and young adults (1 month to 21 years). The aim of this study is to confirm the recommended doses and evaluate the drug’s safety and pharmacodynamics in adults over aged 21. Each participant will receive six 2-hour infusions of calaspargase pegol over several months. The primary outcomes are safety and drug activity; OS is a secondary outcome and QoL will not be measured. The study opened on July 7 and aims to recruit 122 participants in 11 states.

Untreated adults with TP53-mutant AML

Adult patients with previously untreated AML who have at least one TP53 gene mutation are sought for a phase 3 study of magrolimab, an investigational anti-CD47 monoclonal antibody. Participants will be treated for up to 27 months with either magrolimab plus azacytidine (Vidaza), venetoclax plus azacytidine (patients deemed “appropriate for nonintensive therapy”), or standard chemotherapy (those “appropriate for intensive therapy”). In patients who received nonintensive therapy, OS is the primary outcome; OS in all participants is a secondary outcome, and QoL won’t be assessed. The trial opened in July and aims to recruit 346 individuals in Hong Kong, Australia, and the United States (California, Missouri, Oklahoma, Pennsylvania, South Carolina, and Texas).

All trial information is from the U.S. National Library of Medicine, National Institutes of Health.

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

A number of late-phase clinical trials in leukemia have opened in recent months. Maybe one of your patients could benefit from being enrolled.

Adults and children with acute or chronic leukemias

A phase 2 study partnering with the National Marrow Donor Program is seeking individuals aged 1-65 years with lymphoma or one of the following leukemias: “acute leukemia”, acute lymphoblastic (ALL), acute myelogenous (AML), mixed-phenotype acute, chronic myelogenous (CML), and chronic lymphocytic (CLL). Researchers hope to find a way to improve outcomes of hematopoietic-cell transplantation from mismatched, unrelated donors. Participants will receive the transplant and one of seven drug regimens and will be followed for a year. The trial plans to enroll 180 people and began recruiting on Sept. 30 in California, New York, and Virginia. The primary outcome is overall survival (OS). Quality of life (QoL) will not be measured.

Mast-cell leukemia (MCL)

Adults with MCL are sought for a phase 2 study of bezuclastinib, an experimental tyrosine-kinase inhibitor (TKI) called CGT9486. CGT9486 blocks the activity of a mutated version of tyrosine-kinase receptor KIT, called KIT D816V, which is known to cause systemic mastocytosis. Participants will receive oral CGT9486 daily for up to 18 months. The study opened in October, aiming for 140 participants with any advanced systemic mastocytoses (including MCL) at sites in California, Florida, Massachusetts, New York, Ohio, Texas, and Utah. OS and QoL will be tracked.

Previously Treated CLL/Small Lymphocytic Lymphoma (SLL)

Patients with CLL/SLL who have progressed on previous therapy can join a phase 3 study of another experimental oral TIK, pirtobrutinib, this time targeting Bruton’s tyrosine kinase (BTK). BTK plays a key role in the lifecycle of white blood cells. Participants will receive either “fixed-duration” pirtobrutinib plus venetoclax (Venclexta) and rituximab (Ruxience, Riabni, Truxima, Rituxan, MabThera) or the venetoclax-rituximab combo only, for up to 5 years. Investigators started recruiting in September, aiming for 600 participants across Florida, Louisiana, Missouri, New York, and Tennessee. Progression-free survival is the primary outcome; OS is a secondary outcome and QoL will not be tracked.

High-grade myeloid cancers with measurable residual disease

Patients with AML, myelodysplastic syndrome with excess blasts-2 or myeloid neoplasm, and whose original disease is still present, are eligible for a phase 2 study of CPX-351 (daunorubicin-cytarabine, Vyxeos). The intravenous chemotherapy was approved in 2017 for certain types of AML. The goal of this study is to determine if pretreatment with CPX-351 improves the outcome of donor stem-cell transplantation. Patients will either undergo immediate transplantation or receive CPX-351 for up to 10 days followed 60 days later by the transplant. The study, being conducted at the Fred Hutchinson Cancer Research Center in Seattle, started recruiting 130 patients in August. The primary outcome is OS; QoL will not be tracked.

Newly diagnosed Philadelphia-negative ALL

Patients aged 22 or older with Philadelphia-negative ALL who have not received chemotherapy or radiation therapy are invited to join a trial of calaspargase pegol (Asparlas). The therapy was approved in 2018 for ALL in children and young adults (1 month to 21 years). The aim of this study is to confirm the recommended doses and evaluate the drug’s safety and pharmacodynamics in adults over aged 21. Each participant will receive six 2-hour infusions of calaspargase pegol over several months. The primary outcomes are safety and drug activity; OS is a secondary outcome and QoL will not be measured. The study opened on July 7 and aims to recruit 122 participants in 11 states.

Untreated adults with TP53-mutant AML

Adult patients with previously untreated AML who have at least one TP53 gene mutation are sought for a phase 3 study of magrolimab, an investigational anti-CD47 monoclonal antibody. Participants will be treated for up to 27 months with either magrolimab plus azacytidine (Vidaza), venetoclax plus azacytidine (patients deemed “appropriate for nonintensive therapy”), or standard chemotherapy (those “appropriate for intensive therapy”). In patients who received nonintensive therapy, OS is the primary outcome; OS in all participants is a secondary outcome, and QoL won’t be assessed. The trial opened in July and aims to recruit 346 individuals in Hong Kong, Australia, and the United States (California, Missouri, Oklahoma, Pennsylvania, South Carolina, and Texas).

All trial information is from the U.S. National Library of Medicine, National Institutes of Health.

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

A number of late-phase clinical trials in leukemia have opened in recent months. Maybe one of your patients could benefit from being enrolled.

Adults and children with acute or chronic leukemias

A phase 2 study partnering with the National Marrow Donor Program is seeking individuals aged 1-65 years with lymphoma or one of the following leukemias: “acute leukemia”, acute lymphoblastic (ALL), acute myelogenous (AML), mixed-phenotype acute, chronic myelogenous (CML), and chronic lymphocytic (CLL). Researchers hope to find a way to improve outcomes of hematopoietic-cell transplantation from mismatched, unrelated donors. Participants will receive the transplant and one of seven drug regimens and will be followed for a year. The trial plans to enroll 180 people and began recruiting on Sept. 30 in California, New York, and Virginia. The primary outcome is overall survival (OS). Quality of life (QoL) will not be measured.

Mast-cell leukemia (MCL)

Adults with MCL are sought for a phase 2 study of bezuclastinib, an experimental tyrosine-kinase inhibitor (TKI) called CGT9486. CGT9486 blocks the activity of a mutated version of tyrosine-kinase receptor KIT, called KIT D816V, which is known to cause systemic mastocytosis. Participants will receive oral CGT9486 daily for up to 18 months. The study opened in October, aiming for 140 participants with any advanced systemic mastocytoses (including MCL) at sites in California, Florida, Massachusetts, New York, Ohio, Texas, and Utah. OS and QoL will be tracked.

Previously Treated CLL/Small Lymphocytic Lymphoma (SLL)

Patients with CLL/SLL who have progressed on previous therapy can join a phase 3 study of another experimental oral TIK, pirtobrutinib, this time targeting Bruton’s tyrosine kinase (BTK). BTK plays a key role in the lifecycle of white blood cells. Participants will receive either “fixed-duration” pirtobrutinib plus venetoclax (Venclexta) and rituximab (Ruxience, Riabni, Truxima, Rituxan, MabThera) or the venetoclax-rituximab combo only, for up to 5 years. Investigators started recruiting in September, aiming for 600 participants across Florida, Louisiana, Missouri, New York, and Tennessee. Progression-free survival is the primary outcome; OS is a secondary outcome and QoL will not be tracked.

High-grade myeloid cancers with measurable residual disease

Patients with AML, myelodysplastic syndrome with excess blasts-2 or myeloid neoplasm, and whose original disease is still present, are eligible for a phase 2 study of CPX-351 (daunorubicin-cytarabine, Vyxeos). The intravenous chemotherapy was approved in 2017 for certain types of AML. The goal of this study is to determine if pretreatment with CPX-351 improves the outcome of donor stem-cell transplantation. Patients will either undergo immediate transplantation or receive CPX-351 for up to 10 days followed 60 days later by the transplant. The study, being conducted at the Fred Hutchinson Cancer Research Center in Seattle, started recruiting 130 patients in August. The primary outcome is OS; QoL will not be tracked.

Newly diagnosed Philadelphia-negative ALL

Patients aged 22 or older with Philadelphia-negative ALL who have not received chemotherapy or radiation therapy are invited to join a trial of calaspargase pegol (Asparlas). The therapy was approved in 2018 for ALL in children and young adults (1 month to 21 years). The aim of this study is to confirm the recommended doses and evaluate the drug’s safety and pharmacodynamics in adults over aged 21. Each participant will receive six 2-hour infusions of calaspargase pegol over several months. The primary outcomes are safety and drug activity; OS is a secondary outcome and QoL will not be measured. The study opened on July 7 and aims to recruit 122 participants in 11 states.

Untreated adults with TP53-mutant AML

Adult patients with previously untreated AML who have at least one TP53 gene mutation are sought for a phase 3 study of magrolimab, an investigational anti-CD47 monoclonal antibody. Participants will be treated for up to 27 months with either magrolimab plus azacytidine (Vidaza), venetoclax plus azacytidine (patients deemed “appropriate for nonintensive therapy”), or standard chemotherapy (those “appropriate for intensive therapy”). In patients who received nonintensive therapy, OS is the primary outcome; OS in all participants is a secondary outcome, and QoL won’t be assessed. The trial opened in July and aims to recruit 346 individuals in Hong Kong, Australia, and the United States (California, Missouri, Oklahoma, Pennsylvania, South Carolina, and Texas).

All trial information is from the U.S. National Library of Medicine, National Institutes of Health.

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