AML

Key clinical point: Mutation in isocitrate dehydrogenase 2 (IDH2) gene predicted a favorable response to daunorubicin, cytarabine, and cladribine (DAC) regimen in patients with normal karyotype acute myeloid leukemia (NK-AML).

Major finding: IDH2 mutation had a positive impact on overall survival in patients treated with DAC regimen (54% vs. 33%; P = .0087) but not in those treated with daunorubicin+cytarabine (DA; 21% vs. 23%; P = .22) regimen. Moreover, DAC induction was independently associated with a reduced risk for death when the observations were censored at allogeneic hematopoietic stem cell transplant (hazard ratio, 0.21; P = .02).

Study details: Findings are from a retrospective analysis of 398 patients with NK-AML (IDH2⁺, n=50) treated with DA (48%), DAC (44%), or DA+fludarabine (8%) regimens.

Disclosures: This study was supported by grants from the Polish Ministry of Science and Education, Polish National Center for Research and Development, and Nicolaus Copernicus University in Bydgoszcz. The authors declared no conflicts of interest.

Source: Libura M et al. Sci Rep. 2021 May 11. doi: 10.1038/s41598-021-88120-y.

Key clinical point: Mutation in isocitrate dehydrogenase 2 (IDH2) gene predicted a favorable response to daunorubicin, cytarabine, and cladribine (DAC) regimen in patients with normal karyotype acute myeloid leukemia (NK-AML).

Major finding: IDH2 mutation had a positive impact on overall survival in patients treated with DAC regimen (54% vs. 33%; P = .0087) but not in those treated with daunorubicin+cytarabine (DA; 21% vs. 23%; P = .22) regimen. Moreover, DAC induction was independently associated with a reduced risk for death when the observations were censored at allogeneic hematopoietic stem cell transplant (hazard ratio, 0.21; P = .02).

Study details: Findings are from a retrospective analysis of 398 patients with NK-AML (IDH2⁺, n=50) treated with DA (48%), DAC (44%), or DA+fludarabine (8%) regimens.

Disclosures: This study was supported by grants from the Polish Ministry of Science and Education, Polish National Center for Research and Development, and Nicolaus Copernicus University in Bydgoszcz. The authors declared no conflicts of interest.

Source: Libura M et al. Sci Rep. 2021 May 11. doi: 10.1038/s41598-021-88120-y.

Key clinical point: Mutation in isocitrate dehydrogenase 2 (IDH2) gene predicted a favorable response to daunorubicin, cytarabine, and cladribine (DAC) regimen in patients with normal karyotype acute myeloid leukemia (NK-AML).

Major finding: IDH2 mutation had a positive impact on overall survival in patients treated with DAC regimen (54% vs. 33%; P = .0087) but not in those treated with daunorubicin+cytarabine (DA; 21% vs. 23%; P = .22) regimen. Moreover, DAC induction was independently associated with a reduced risk for death when the observations were censored at allogeneic hematopoietic stem cell transplant (hazard ratio, 0.21; P = .02).

Study details: Findings are from a retrospective analysis of 398 patients with NK-AML (IDH2⁺, n=50) treated with DA (48%), DAC (44%), or DA+fludarabine (8%) regimens.

Disclosures: This study was supported by grants from the Polish Ministry of Science and Education, Polish National Center for Research and Development, and Nicolaus Copernicus University in Bydgoszcz. The authors declared no conflicts of interest.

Source: Libura M et al. Sci Rep. 2021 May 11. doi: 10.1038/s41598-021-88120-y.

Key clinical point: In patients with newly diagnosed and relapsed/refractory (R/R) acute myeloid leukemia (AML) evolving from myeloproliferative neoplasms (MPNs), treatment with venetoclax-based (VEN-b) regimens led to modest clinical responses with no substantial improvement in survival, but high treatment-associated hematologic toxicity and mortality.

Major finding: Median overall survival from initiation of VEN-b regimen was 4 (95% confidence interval, 2-8) months with 8-week mortality being 32%. Only 7 patients with newly diagnosed AML achieved a response, with 3 achieving complete remission, 3 achieving complete remission with incomplete count recovery, and 1 achieving partial remission. Grade 3 or higher infections were observed in 84% of patients during the initial treatment cycle, with severe hemorrhagic complications in 45% of patients.

Study details: Findings are from a retrospective analysis of 31 patients with newly diagnosed (n=14) or R/R (n=17) post-MPN-AML who were treated with VEN-b therapies.

Disclosures: This study was supported partly by a Cancer Center Support Grant from the National Cancer Institute, National Institutes of Health to MD Anderson Cancer Center. Some investigators reported financial and nonfinancial ties with various pharmaceutical companies.

Source: Masarova L et al. Blood Adv. 2021 Apr 22. doi: 10.1182/bloodadvances.2020003934.

Key clinical point: In patients with newly diagnosed and relapsed/refractory (R/R) acute myeloid leukemia (AML) evolving from myeloproliferative neoplasms (MPNs), treatment with venetoclax-based (VEN-b) regimens led to modest clinical responses with no substantial improvement in survival, but high treatment-associated hematologic toxicity and mortality.

Major finding: Median overall survival from initiation of VEN-b regimen was 4 (95% confidence interval, 2-8) months with 8-week mortality being 32%. Only 7 patients with newly diagnosed AML achieved a response, with 3 achieving complete remission, 3 achieving complete remission with incomplete count recovery, and 1 achieving partial remission. Grade 3 or higher infections were observed in 84% of patients during the initial treatment cycle, with severe hemorrhagic complications in 45% of patients.

Study details: Findings are from a retrospective analysis of 31 patients with newly diagnosed (n=14) or R/R (n=17) post-MPN-AML who were treated with VEN-b therapies.

Disclosures: This study was supported partly by a Cancer Center Support Grant from the National Cancer Institute, National Institutes of Health to MD Anderson Cancer Center. Some investigators reported financial and nonfinancial ties with various pharmaceutical companies.

Source: Masarova L et al. Blood Adv. 2021 Apr 22. doi: 10.1182/bloodadvances.2020003934.

Key clinical point: In patients with newly diagnosed and relapsed/refractory (R/R) acute myeloid leukemia (AML) evolving from myeloproliferative neoplasms (MPNs), treatment with venetoclax-based (VEN-b) regimens led to modest clinical responses with no substantial improvement in survival, but high treatment-associated hematologic toxicity and mortality.

Major finding: Median overall survival from initiation of VEN-b regimen was 4 (95% confidence interval, 2-8) months with 8-week mortality being 32%. Only 7 patients with newly diagnosed AML achieved a response, with 3 achieving complete remission, 3 achieving complete remission with incomplete count recovery, and 1 achieving partial remission. Grade 3 or higher infections were observed in 84% of patients during the initial treatment cycle, with severe hemorrhagic complications in 45% of patients.

Study details: Findings are from a retrospective analysis of 31 patients with newly diagnosed (n=14) or R/R (n=17) post-MPN-AML who were treated with VEN-b therapies.

Disclosures: This study was supported partly by a Cancer Center Support Grant from the National Cancer Institute, National Institutes of Health to MD Anderson Cancer Center. Some investigators reported financial and nonfinancial ties with various pharmaceutical companies.

Source: Masarova L et al. Blood Adv. 2021 Apr 22. doi: 10.1182/bloodadvances.2020003934.

Key clinical point: Treatment with a combination of hypomethylating agents (HMA) and venetoclax (VEN) was similarly effective in patients with acute myeloid leukemia (AML) with or without spliceosome mutations with specific mutational pairs demonstrating favorable outcomes.

Major finding: Overall response rate (89% vs. 79%; P = .32), composite complete response (79% vs. 75%; P = .65), and median overall survival (OS; 35 vs. 14 months; P = .58) were not significantly different in patients with vs. without spliceosome mutations. Co-occurrence of IDH2 and SRSF2 mutations was associated with favorable outcomes (1- and 2-year OS, 100% and 88%, respectively).

Study details: Findings are from a retrospective study of 119 adult patients with AML treated with frontline HMA+VEN-based therapy. Mutation in the spliceosome gene was observed in 39 patients.

Disclosures: No specific funding source was identified. Some investigators reported research funding, support, honoraria, consultancy, and advisory roles for various pharmaceutical companies.

Source: Lachowiez CA et al. Blood Adv. 2021 Apr 22. doi: 10.1182/bloodadvances.2020004173.

Key clinical point: Treatment with a combination of hypomethylating agents (HMA) and venetoclax (VEN) was similarly effective in patients with acute myeloid leukemia (AML) with or without spliceosome mutations with specific mutational pairs demonstrating favorable outcomes.

Major finding: Overall response rate (89% vs. 79%; P = .32), composite complete response (79% vs. 75%; P = .65), and median overall survival (OS; 35 vs. 14 months; P = .58) were not significantly different in patients with vs. without spliceosome mutations. Co-occurrence of IDH2 and SRSF2 mutations was associated with favorable outcomes (1- and 2-year OS, 100% and 88%, respectively).

Study details: Findings are from a retrospective study of 119 adult patients with AML treated with frontline HMA+VEN-based therapy. Mutation in the spliceosome gene was observed in 39 patients.

Disclosures: No specific funding source was identified. Some investigators reported research funding, support, honoraria, consultancy, and advisory roles for various pharmaceutical companies.

Source: Lachowiez CA et al. Blood Adv. 2021 Apr 22. doi: 10.1182/bloodadvances.2020004173.

Key clinical point: Treatment with a combination of hypomethylating agents (HMA) and venetoclax (VEN) was similarly effective in patients with acute myeloid leukemia (AML) with or without spliceosome mutations with specific mutational pairs demonstrating favorable outcomes.

Major finding: Overall response rate (89% vs. 79%; P = .32), composite complete response (79% vs. 75%; P = .65), and median overall survival (OS; 35 vs. 14 months; P = .58) were not significantly different in patients with vs. without spliceosome mutations. Co-occurrence of IDH2 and SRSF2 mutations was associated with favorable outcomes (1- and 2-year OS, 100% and 88%, respectively).

Study details: Findings are from a retrospective study of 119 adult patients with AML treated with frontline HMA+VEN-based therapy. Mutation in the spliceosome gene was observed in 39 patients.

Disclosures: No specific funding source was identified. Some investigators reported research funding, support, honoraria, consultancy, and advisory roles for various pharmaceutical companies.

Source: Lachowiez CA et al. Blood Adv. 2021 Apr 22. doi: 10.1182/bloodadvances.2020004173.

Key clinical point: Low-intensity chemotherapy with clofarabine or cladribine and low-dose cytarabine (LDAC) alternating with decitabine was effective and safe for the treatment of older patients with newly diagnosed acute myeloid leukemia (AML).

Major finding: Overall, response was observed in 66% of patients, with complete remission (CR) and CR with incomplete count recovery in 59% and 7% of patients, respectively. The 4- and 8-week mortality was low at 2% and 11%, respectively. During median follow-up of 60 months, the median overall survival was 12.5 months.

Study details: This study assessed 248 older patients (median age, 69 years) with newly diagnosed AML who were treated with either clofarabine (n=119) or cladribine (n=129) combined with LDAC alternating with decitabine.

Disclosures: This study was funded by the MD Anderson Cancer Center Support and the Charif Souki Cancer Research Fund. Some investigators including the lead author reported ties with various pharmaceutical companies.

Source: Kadia TM et al. Am J Hematol. 2021 Apr 26. doi: 10.1002/ajh.26206.

Key clinical point: Low-intensity chemotherapy with clofarabine or cladribine and low-dose cytarabine (LDAC) alternating with decitabine was effective and safe for the treatment of older patients with newly diagnosed acute myeloid leukemia (AML).

Major finding: Overall, response was observed in 66% of patients, with complete remission (CR) and CR with incomplete count recovery in 59% and 7% of patients, respectively. The 4- and 8-week mortality was low at 2% and 11%, respectively. During median follow-up of 60 months, the median overall survival was 12.5 months.

Study details: This study assessed 248 older patients (median age, 69 years) with newly diagnosed AML who were treated with either clofarabine (n=119) or cladribine (n=129) combined with LDAC alternating with decitabine.

Disclosures: This study was funded by the MD Anderson Cancer Center Support and the Charif Souki Cancer Research Fund. Some investigators including the lead author reported ties with various pharmaceutical companies.

Source: Kadia TM et al. Am J Hematol. 2021 Apr 26. doi: 10.1002/ajh.26206.

Key clinical point: Low-intensity chemotherapy with clofarabine or cladribine and low-dose cytarabine (LDAC) alternating with decitabine was effective and safe for the treatment of older patients with newly diagnosed acute myeloid leukemia (AML).

Major finding: Overall, response was observed in 66% of patients, with complete remission (CR) and CR with incomplete count recovery in 59% and 7% of patients, respectively. The 4- and 8-week mortality was low at 2% and 11%, respectively. During median follow-up of 60 months, the median overall survival was 12.5 months.

Study details: This study assessed 248 older patients (median age, 69 years) with newly diagnosed AML who were treated with either clofarabine (n=119) or cladribine (n=129) combined with LDAC alternating with decitabine.

Disclosures: This study was funded by the MD Anderson Cancer Center Support and the Charif Souki Cancer Research Fund. Some investigators including the lead author reported ties with various pharmaceutical companies.

Source: Kadia TM et al. Am J Hematol. 2021 Apr 26. doi: 10.1002/ajh.26206.

Key clinical point: In patients with relapsed/refractory acute myeloid leukemia (AML), mivebresib (MIV) was tolerated and showed antileukemic activity as monotherapy (MIV-mono) and in combination with venetoclax (MIV-Ven).

Major finding: In the MIV-mono cohort, response included complete remission with incomplete blood count recovery (5%) and resistant disease (79%). In patients receiving MIV-Ven, responses were complete remission (7%), partial remission (7%), leukemia-free state (7%), resistant disease (40%), and aplasia (3%). Treatment-emergent adverse events (TEAEs) were reported in 100% of patients, with serious TEAEs in 74%, 88%, and 40% of patients in MIV-mono, MIV-Ven, and patients who switched from MIV-mono to MIV-Ven groups, respectively.

Study details: Findings are from phase 1 study including 44 adult patients with relapsed/refractory AML who received either MIV-mono (n=19) or MIV-Ven (n=25). Because of disease progression, 5 patients switched from MIV-mono to MIV-Ven.

Disclosures: This study was funded by AbbVie. Investigators including the lead author reported ties with various pharmaceutical companies including AbbVie.

Source: Borthakur G et al. Cancer. 2021 May 2. doi: 10.1002/cncr.33590.

Key clinical point: In patients with relapsed/refractory acute myeloid leukemia (AML), mivebresib (MIV) was tolerated and showed antileukemic activity as monotherapy (MIV-mono) and in combination with venetoclax (MIV-Ven).

Major finding: In the MIV-mono cohort, response included complete remission with incomplete blood count recovery (5%) and resistant disease (79%). In patients receiving MIV-Ven, responses were complete remission (7%), partial remission (7%), leukemia-free state (7%), resistant disease (40%), and aplasia (3%). Treatment-emergent adverse events (TEAEs) were reported in 100% of patients, with serious TEAEs in 74%, 88%, and 40% of patients in MIV-mono, MIV-Ven, and patients who switched from MIV-mono to MIV-Ven groups, respectively.

Study details: Findings are from phase 1 study including 44 adult patients with relapsed/refractory AML who received either MIV-mono (n=19) or MIV-Ven (n=25). Because of disease progression, 5 patients switched from MIV-mono to MIV-Ven.

Disclosures: This study was funded by AbbVie. Investigators including the lead author reported ties with various pharmaceutical companies including AbbVie.

Source: Borthakur G et al. Cancer. 2021 May 2. doi: 10.1002/cncr.33590.

Key clinical point: In patients with relapsed/refractory acute myeloid leukemia (AML), mivebresib (MIV) was tolerated and showed antileukemic activity as monotherapy (MIV-mono) and in combination with venetoclax (MIV-Ven).

Major finding: In the MIV-mono cohort, response included complete remission with incomplete blood count recovery (5%) and resistant disease (79%). In patients receiving MIV-Ven, responses were complete remission (7%), partial remission (7%), leukemia-free state (7%), resistant disease (40%), and aplasia (3%). Treatment-emergent adverse events (TEAEs) were reported in 100% of patients, with serious TEAEs in 74%, 88%, and 40% of patients in MIV-mono, MIV-Ven, and patients who switched from MIV-mono to MIV-Ven groups, respectively.

Study details: Findings are from phase 1 study including 44 adult patients with relapsed/refractory AML who received either MIV-mono (n=19) or MIV-Ven (n=25). Because of disease progression, 5 patients switched from MIV-mono to MIV-Ven.

Disclosures: This study was funded by AbbVie. Investigators including the lead author reported ties with various pharmaceutical companies including AbbVie.

Source: Borthakur G et al. Cancer. 2021 May 2. doi: 10.1002/cncr.33590.

Key clinical point: Addition of tosedostat to low-dose cytosine arabinoside (LDAC) did not confer any additional clinical benefit compared with LDAC alone in older patients with acute myeloid leukemia (AML) unfit for intensive chemotherapy.

Major finding: There was no significant benefit of adding tosedostat to LDAC vs. LDAC alone on overall response (25% vs. 18%; P = .22) and 2-year overall survival (16% vs. 12%; P = .8). Overall rates of grade 3 or higher toxicity were low, but diarrhea and cardiac toxicity were significantly higher with tosedostat.

Study details: Findings are from LI-1 trial including 243 older (age, 60 years or older) patients with de novo or secondary AML or high-risk myelodysplastic syndrome who were unfit for intensive chemotherapy. Patients were randomly allocated to receive either LDAC (n=121) or LDAC+tosedostat (n=122).

Disclosures: This study was supported by CTI Biopharma, Blood Cancer UK, the Haematology Clinical Trials Unit, and the Centre for Trials Research, Cardiff University. No author disclosures were reported.

Source: Dennis M et al. Br J Haematol. 2021 May 7. doi: 10.1111/bjh.17501.

Key clinical point: Addition of tosedostat to low-dose cytosine arabinoside (LDAC) did not confer any additional clinical benefit compared with LDAC alone in older patients with acute myeloid leukemia (AML) unfit for intensive chemotherapy.

Major finding: There was no significant benefit of adding tosedostat to LDAC vs. LDAC alone on overall response (25% vs. 18%; P = .22) and 2-year overall survival (16% vs. 12%; P = .8). Overall rates of grade 3 or higher toxicity were low, but diarrhea and cardiac toxicity were significantly higher with tosedostat.

Study details: Findings are from LI-1 trial including 243 older (age, 60 years or older) patients with de novo or secondary AML or high-risk myelodysplastic syndrome who were unfit for intensive chemotherapy. Patients were randomly allocated to receive either LDAC (n=121) or LDAC+tosedostat (n=122).

Disclosures: This study was supported by CTI Biopharma, Blood Cancer UK, the Haematology Clinical Trials Unit, and the Centre for Trials Research, Cardiff University. No author disclosures were reported.

Source: Dennis M et al. Br J Haematol. 2021 May 7. doi: 10.1111/bjh.17501.

Key clinical point: Addition of tosedostat to low-dose cytosine arabinoside (LDAC) did not confer any additional clinical benefit compared with LDAC alone in older patients with acute myeloid leukemia (AML) unfit for intensive chemotherapy.

Major finding: There was no significant benefit of adding tosedostat to LDAC vs. LDAC alone on overall response (25% vs. 18%; P = .22) and 2-year overall survival (16% vs. 12%; P = .8). Overall rates of grade 3 or higher toxicity were low, but diarrhea and cardiac toxicity were significantly higher with tosedostat.

Study details: Findings are from LI-1 trial including 243 older (age, 60 years or older) patients with de novo or secondary AML or high-risk myelodysplastic syndrome who were unfit for intensive chemotherapy. Patients were randomly allocated to receive either LDAC (n=121) or LDAC+tosedostat (n=122).

Disclosures: This study was supported by CTI Biopharma, Blood Cancer UK, the Haematology Clinical Trials Unit, and the Centre for Trials Research, Cardiff University. No author disclosures were reported.

Source: Dennis M et al. Br J Haematol. 2021 May 7. doi: 10.1111/bjh.17501.

Key clinical point: In the absence of human leukocyte antigen-matched donors, allogeneic hematopoietic cell transplantation (allo-HCT) using a mismatched unrelated donor (MMUD) with posttransplant cyclophosphamide (PTCy) yielded better survival outcomes vs. cord blood transplantation (CBT) in patients with acute myeloid leukemia (AML).

Major finding: CBT was associated with a significantly higher risk for nonrelapse mortality (adjusted hazard ratio [aHR], 2.09), worse leukemia-free survival (aHR, 1.68), and overall survival (aHR, 1.70) vs. MMUD (all P less than .0001).

Study details: This study included adult patients with AML who underwent a first allo-HCT using CBT (n=902) or single-allele MMUD with PTCy (n=280) between 2010 and 2019.

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

Source: Dholaria B et al. J Hematol Oncol. 2021 May 3. doi: 10.1186/s13045-021-01086-2.

Key clinical point: In the absence of human leukocyte antigen-matched donors, allogeneic hematopoietic cell transplantation (allo-HCT) using a mismatched unrelated donor (MMUD) with posttransplant cyclophosphamide (PTCy) yielded better survival outcomes vs. cord blood transplantation (CBT) in patients with acute myeloid leukemia (AML).

Major finding: CBT was associated with a significantly higher risk for nonrelapse mortality (adjusted hazard ratio [aHR], 2.09), worse leukemia-free survival (aHR, 1.68), and overall survival (aHR, 1.70) vs. MMUD (all P less than .0001).

Study details: This study included adult patients with AML who underwent a first allo-HCT using CBT (n=902) or single-allele MMUD with PTCy (n=280) between 2010 and 2019.

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

Source: Dholaria B et al. J Hematol Oncol. 2021 May 3. doi: 10.1186/s13045-021-01086-2.

Key clinical point: In the absence of human leukocyte antigen-matched donors, allogeneic hematopoietic cell transplantation (allo-HCT) using a mismatched unrelated donor (MMUD) with posttransplant cyclophosphamide (PTCy) yielded better survival outcomes vs. cord blood transplantation (CBT) in patients with acute myeloid leukemia (AML).

Major finding: CBT was associated with a significantly higher risk for nonrelapse mortality (adjusted hazard ratio [aHR], 2.09), worse leukemia-free survival (aHR, 1.68), and overall survival (aHR, 1.70) vs. MMUD (all P less than .0001).

Study details: This study included adult patients with AML who underwent a first allo-HCT using CBT (n=902) or single-allele MMUD with PTCy (n=280) between 2010 and 2019.

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

Source: Dholaria B et al. J Hematol Oncol. 2021 May 3. doi: 10.1186/s13045-021-01086-2.

Several studies published this month have shed some more light on the treatment and prognosis of certain molecular subgroups such as FLT3, spliceasome mutations and IDH mutation. A study from MD Anderson Cancer Center (MDACC) demonstrated the efficacy of FLT33 inhibitors in the treatment of patients with very low allelic burden. Patients who recived both a FMS-like tyrosine kinase inhibitor (FLT3i) during induction and an allogeneic HCT at time of first remission had better 5 year overall survival (OS) (100%) than those who received neither (27%). The 5-year OS rate among patients who did not receive FLT3i-based induction but underwent allo-SCT in CR1 was 71%. None of the patients who received a FLT3i had detectable FLT3 at time of relapse, compared to 67% for those who did not. The main weakness of the study is the small number of patients (total of 50 patients). This study however does provide some provocative data regarding the validity of the FLT3 allelic ratio in decisions regarding treatment and prognosis. The results of this study need to be validated in a larger cohort of patients.

A study by Lachowiez et al, further refined the prognostic significance of spliceosome mutations in patients treated with ven + HMA. Of the 119 patients, 39 had spliceosome mutations. The overall response and prognosis was not different between patients with and without spliceosome mutations. However, SRSF2 was associated with IDH2 mutation and the median OS was not reached vs, patient with U2AF1 who had a higher association with RAS mutations (OS 8 months). The prognostic role of standard cytotoxic chemotherapy in improving the outcome of patients with an IDH mutation was studied by the group. In a re-evaluation of the randomized trial comparing the addition of fludarabine or cladrbaine to standard 7 +3, 50 patients with an IDH mutation were evaluated. Patients with an IDH mutation who received cladribine. IDH2 mutation had a positive impact on OS in patients treated with DAC regimen (54% vs. 33%; P = .0087) but not in those treated with daunorubicin+cytarabine (DA; 21% vs. 23%; P = .22) regimen. Moreover, DAC induction was independently associated with a reduced risk for death when the observations were censored at allogeneic hematopoietic stem cell transplant (hazard ratio, 0.21; P = .02).

Although hypomethylating agents + venetoclax (HMA +ven) have shown efficacy in multiple patient subgroups, the outcome of patients with post-MPN acute myeloid leukemia (AML) remains poor even with HMA + ven. In a retrospective study, 31 patients with post MPN AML were treated with HMA + ven. The overall survival for patients with relapsed post MPN AML was 3 months with none of the 9 patients achieving a CR/CRi. As for the patients with previously untreated post MPN-AML, the median survival was still poor at 8 months with 43% achieving CR/CRi. This study highlights the large unmet need in this patient population. In comparison, in a retrospective study by Piccini et al, of the 47 patients with relapsed/refractory (R/R) AML treated with venetoclax based regimens the composite CR rate was 55%. These outcomes are similar to other studies of venetoclax based regimens in patients with R/R AML. 

In a retrospective study from the European Society for Blood and Marrow Transplantation (EBMT) registry, the outcomes of patients receiving mismatched unrelated donor (MMUD) with post transplant cyclophosphamide (PTCy) had better outcomes compared to patients receiving cord blood transplantation (CBT). The 2 year leukemia free survival (LFS) for CBT vs MMUD was 42.8% vs 60.5% and OS was 46.85 vs 62.8%. This retrospective study demonstrated that PTCy can improve the outcomes of patients receiving of MMUD (Dholaria B et al. J Hematol Oncol. 2021 May).

Several studies published this month have shed some more light on the treatment and prognosis of certain molecular subgroups such as FLT3, spliceasome mutations and IDH mutation. A study from MD Anderson Cancer Center (MDACC) demonstrated the efficacy of FLT33 inhibitors in the treatment of patients with very low allelic burden. Patients who recived both a FMS-like tyrosine kinase inhibitor (FLT3i) during induction and an allogeneic HCT at time of first remission had better 5 year overall survival (OS) (100%) than those who received neither (27%). The 5-year OS rate among patients who did not receive FLT3i-based induction but underwent allo-SCT in CR1 was 71%. None of the patients who received a FLT3i had detectable FLT3 at time of relapse, compared to 67% for those who did not. The main weakness of the study is the small number of patients (total of 50 patients). This study however does provide some provocative data regarding the validity of the FLT3 allelic ratio in decisions regarding treatment and prognosis. The results of this study need to be validated in a larger cohort of patients.

A study by Lachowiez et al, further refined the prognostic significance of spliceosome mutations in patients treated with ven + HMA. Of the 119 patients, 39 had spliceosome mutations. The overall response and prognosis was not different between patients with and without spliceosome mutations. However, SRSF2 was associated with IDH2 mutation and the median OS was not reached vs, patient with U2AF1 who had a higher association with RAS mutations (OS 8 months). The prognostic role of standard cytotoxic chemotherapy in improving the outcome of patients with an IDH mutation was studied by the group. In a re-evaluation of the randomized trial comparing the addition of fludarabine or cladrbaine to standard 7 +3, 50 patients with an IDH mutation were evaluated. Patients with an IDH mutation who received cladribine. IDH2 mutation had a positive impact on OS in patients treated with DAC regimen (54% vs. 33%; P = .0087) but not in those treated with daunorubicin+cytarabine (DA; 21% vs. 23%; P = .22) regimen. Moreover, DAC induction was independently associated with a reduced risk for death when the observations were censored at allogeneic hematopoietic stem cell transplant (hazard ratio, 0.21; P = .02).

Although hypomethylating agents + venetoclax (HMA +ven) have shown efficacy in multiple patient subgroups, the outcome of patients with post-MPN acute myeloid leukemia (AML) remains poor even with HMA + ven. In a retrospective study, 31 patients with post MPN AML were treated with HMA + ven. The overall survival for patients with relapsed post MPN AML was 3 months with none of the 9 patients achieving a CR/CRi. As for the patients with previously untreated post MPN-AML, the median survival was still poor at 8 months with 43% achieving CR/CRi. This study highlights the large unmet need in this patient population. In comparison, in a retrospective study by Piccini et al, of the 47 patients with relapsed/refractory (R/R) AML treated with venetoclax based regimens the composite CR rate was 55%. These outcomes are similar to other studies of venetoclax based regimens in patients with R/R AML. 

In a retrospective study from the European Society for Blood and Marrow Transplantation (EBMT) registry, the outcomes of patients receiving mismatched unrelated donor (MMUD) with post transplant cyclophosphamide (PTCy) had better outcomes compared to patients receiving cord blood transplantation (CBT). The 2 year leukemia free survival (LFS) for CBT vs MMUD was 42.8% vs 60.5% and OS was 46.85 vs 62.8%. This retrospective study demonstrated that PTCy can improve the outcomes of patients receiving of MMUD (Dholaria B et al. J Hematol Oncol. 2021 May).

Several studies published this month have shed some more light on the treatment and prognosis of certain molecular subgroups such as FLT3, spliceasome mutations and IDH mutation. A study from MD Anderson Cancer Center (MDACC) demonstrated the efficacy of FLT33 inhibitors in the treatment of patients with very low allelic burden. Patients who recived both a FMS-like tyrosine kinase inhibitor (FLT3i) during induction and an allogeneic HCT at time of first remission had better 5 year overall survival (OS) (100%) than those who received neither (27%). The 5-year OS rate among patients who did not receive FLT3i-based induction but underwent allo-SCT in CR1 was 71%. None of the patients who received a FLT3i had detectable FLT3 at time of relapse, compared to 67% for those who did not. The main weakness of the study is the small number of patients (total of 50 patients). This study however does provide some provocative data regarding the validity of the FLT3 allelic ratio in decisions regarding treatment and prognosis. The results of this study need to be validated in a larger cohort of patients.

A study by Lachowiez et al, further refined the prognostic significance of spliceosome mutations in patients treated with ven + HMA. Of the 119 patients, 39 had spliceosome mutations. The overall response and prognosis was not different between patients with and without spliceosome mutations. However, SRSF2 was associated with IDH2 mutation and the median OS was not reached vs, patient with U2AF1 who had a higher association with RAS mutations (OS 8 months). The prognostic role of standard cytotoxic chemotherapy in improving the outcome of patients with an IDH mutation was studied by the group. In a re-evaluation of the randomized trial comparing the addition of fludarabine or cladrbaine to standard 7 +3, 50 patients with an IDH mutation were evaluated. Patients with an IDH mutation who received cladribine. IDH2 mutation had a positive impact on OS in patients treated with DAC regimen (54% vs. 33%; P = .0087) but not in those treated with daunorubicin+cytarabine (DA; 21% vs. 23%; P = .22) regimen. Moreover, DAC induction was independently associated with a reduced risk for death when the observations were censored at allogeneic hematopoietic stem cell transplant (hazard ratio, 0.21; P = .02).

Although hypomethylating agents + venetoclax (HMA +ven) have shown efficacy in multiple patient subgroups, the outcome of patients with post-MPN acute myeloid leukemia (AML) remains poor even with HMA + ven. In a retrospective study, 31 patients with post MPN AML were treated with HMA + ven. The overall survival for patients with relapsed post MPN AML was 3 months with none of the 9 patients achieving a CR/CRi. As for the patients with previously untreated post MPN-AML, the median survival was still poor at 8 months with 43% achieving CR/CRi. This study highlights the large unmet need in this patient population. In comparison, in a retrospective study by Piccini et al, of the 47 patients with relapsed/refractory (R/R) AML treated with venetoclax based regimens the composite CR rate was 55%. These outcomes are similar to other studies of venetoclax based regimens in patients with R/R AML. 

In a retrospective study from the European Society for Blood and Marrow Transplantation (EBMT) registry, the outcomes of patients receiving mismatched unrelated donor (MMUD) with post transplant cyclophosphamide (PTCy) had better outcomes compared to patients receiving cord blood transplantation (CBT). The 2 year leukemia free survival (LFS) for CBT vs MMUD was 42.8% vs 60.5% and OS was 46.85 vs 62.8%. This retrospective study demonstrated that PTCy can improve the outcomes of patients receiving of MMUD (Dholaria B et al. J Hematol Oncol. 2021 May).

Key clinical point: Long-term survival in children with acute myeloid leukemia (AML) who receive low-dose chemotherapy (LDC) for remission induction is comparable to that of children who receive standard-dose chemotherapy (SDC).

Major finding:  No significant differences were observed between the LDC and SDC groups in 5-year event-free survival (61.4% ± 8.7% vs 65.2% ± 7.4%, respectively; P = .462), overall survival (72.7% ± 6.9% vs 72.5% ± 6.2%, respectively; P = .933), and the incidence of relapse (20.5% ± 4.5% vs 17.6% ± 3.9%, respectively; P = .484).

Study details: Long-term follow-up of 83 patients with AML treated with a LDC regimen (and 100 children with AML treated with a standard-dose chemotherapy (SDC) regimen.

Disclosures: This work was supported by NSCF, the Key Research Program of the Chinese Academy of Sciences, the Jiangsu Province Foundation, the National Clinical Research Center for Hematological Disorders, and the Youth Innovation Promotion Association of Chinese Academy of Sciences. The authors declared no conflicts of interest.

Source: Hu Y et al. Blood Adv. 2021 Apr 13. doi: 10.1182/bloodadvances.2020003453.

Key clinical point: Long-term survival in children with acute myeloid leukemia (AML) who receive low-dose chemotherapy (LDC) for remission induction is comparable to that of children who receive standard-dose chemotherapy (SDC).

Major finding:  No significant differences were observed between the LDC and SDC groups in 5-year event-free survival (61.4% ± 8.7% vs 65.2% ± 7.4%, respectively; P = .462), overall survival (72.7% ± 6.9% vs 72.5% ± 6.2%, respectively; P = .933), and the incidence of relapse (20.5% ± 4.5% vs 17.6% ± 3.9%, respectively; P = .484).

Study details: Long-term follow-up of 83 patients with AML treated with a LDC regimen (and 100 children with AML treated with a standard-dose chemotherapy (SDC) regimen.

Disclosures: This work was supported by NSCF, the Key Research Program of the Chinese Academy of Sciences, the Jiangsu Province Foundation, the National Clinical Research Center for Hematological Disorders, and the Youth Innovation Promotion Association of Chinese Academy of Sciences. The authors declared no conflicts of interest.

Source: Hu Y et al. Blood Adv. 2021 Apr 13. doi: 10.1182/bloodadvances.2020003453.

Key clinical point: Long-term survival in children with acute myeloid leukemia (AML) who receive low-dose chemotherapy (LDC) for remission induction is comparable to that of children who receive standard-dose chemotherapy (SDC).

Major finding:  No significant differences were observed between the LDC and SDC groups in 5-year event-free survival (61.4% ± 8.7% vs 65.2% ± 7.4%, respectively; P = .462), overall survival (72.7% ± 6.9% vs 72.5% ± 6.2%, respectively; P = .933), and the incidence of relapse (20.5% ± 4.5% vs 17.6% ± 3.9%, respectively; P = .484).

Study details: Long-term follow-up of 83 patients with AML treated with a LDC regimen (and 100 children with AML treated with a standard-dose chemotherapy (SDC) regimen.

Disclosures: This work was supported by NSCF, the Key Research Program of the Chinese Academy of Sciences, the Jiangsu Province Foundation, the National Clinical Research Center for Hematological Disorders, and the Youth Innovation Promotion Association of Chinese Academy of Sciences. The authors declared no conflicts of interest.

Source: Hu Y et al. Blood Adv. 2021 Apr 13. doi: 10.1182/bloodadvances.2020003453.

Key clinical point: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) may improve survival outcomes in acute myeloid leukemia (AML) patients with ASXL1 mutations.

Major finding: In multivariate analysis, ASXL1 mutation was found to be an independent prognostic factor for overall survival (OS; hazard ratio [HR], 2.248; P = .017). Furthermore, Allo-HSCT was associated with significant improvements in overall survival (HR 7.568; P less than .001) and disease-free survival (HR, 2.611; P less than .001) in ASXL1-mutated ALL patients.

Study details: Analysis of the prognostic value of ASXL1 mutations and the role of allo-HSCT in 581 patients with AML.

Disclosures: The study was supported by grants from the National Natural Science Foundation of China, the Natural Science Foundation of Jiangsu Province, the Social Development Project of Jiangsu Province, the Priority Academic Program Development of Jiangsu Higher Education Institutions, and the National Key Research and Development Program. The authors declared no conflicts of interest.

Source: Zhou L et al. Hematology. 2021 Apr 10. doi: 10.1080/16078454.2021.1905356.

Key clinical point: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) may improve survival outcomes in acute myeloid leukemia (AML) patients with ASXL1 mutations.

Major finding: In multivariate analysis, ASXL1 mutation was found to be an independent prognostic factor for overall survival (OS; hazard ratio [HR], 2.248; P = .017). Furthermore, Allo-HSCT was associated with significant improvements in overall survival (HR 7.568; P less than .001) and disease-free survival (HR, 2.611; P less than .001) in ASXL1-mutated ALL patients.

Study details: Analysis of the prognostic value of ASXL1 mutations and the role of allo-HSCT in 581 patients with AML.

Disclosures: The study was supported by grants from the National Natural Science Foundation of China, the Natural Science Foundation of Jiangsu Province, the Social Development Project of Jiangsu Province, the Priority Academic Program Development of Jiangsu Higher Education Institutions, and the National Key Research and Development Program. The authors declared no conflicts of interest.

Source: Zhou L et al. Hematology. 2021 Apr 10. doi: 10.1080/16078454.2021.1905356.

Key clinical point: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) may improve survival outcomes in acute myeloid leukemia (AML) patients with ASXL1 mutations.

Major finding: In multivariate analysis, ASXL1 mutation was found to be an independent prognostic factor for overall survival (OS; hazard ratio [HR], 2.248; P = .017). Furthermore, Allo-HSCT was associated with significant improvements in overall survival (HR 7.568; P less than .001) and disease-free survival (HR, 2.611; P less than .001) in ASXL1-mutated ALL patients.

Study details: Analysis of the prognostic value of ASXL1 mutations and the role of allo-HSCT in 581 patients with AML.

Disclosures: The study was supported by grants from the National Natural Science Foundation of China, the Natural Science Foundation of Jiangsu Province, the Social Development Project of Jiangsu Province, the Priority Academic Program Development of Jiangsu Higher Education Institutions, and the National Key Research and Development Program. The authors declared no conflicts of interest.

Source: Zhou L et al. Hematology. 2021 Apr 10. doi: 10.1080/16078454.2021.1905356.