Additional information and data in acute leukemia

December 12, 2020

In addition to the highlights from ASH 2019 (, EHA 2020 (
), EMBT 2020 ( and ESMO 2020 (, here are some additional information and data in acute leukemia published over the past year:

October 2019

After the approval by the FDA in November 2018, the European Commission approved the oral FLT3/AXL inhibitor gilteritinib as a single agent for the treatment of adult patients with relapsed or refractory AML with an FLT3 mutation. The agency’s decision was based on results from the randomized, open-label, phase III ADMIRAL trial, which compared the safety and efficacy of gilteritinib with salvage chemotherapy in 371 adults with relapsed or refractory FLT3-mutated AML. (Source: Astellas press release, October 25, 2019)

Updated results from the APL0406 study suggest that the combination of all-trans retinoic acid (ATRA) plus arsenic trioxide was associated with greater long-term event-free survival and disease-free survival in patients with low- and intermediate-risk APL compared with ATRA plus chemotherapy. (Ref. Cicconi L, Platzbecker U, Avvisati G, et al. Long-term results of all-trans retinoic acid and arsenic trioxide in non-high-risk acute promyelocytic leukemia: update of the APL0406 Italian-German randomized trial. Leukemia. 2019 October 14)

December 2019


The IDH1 inhibitor olutasidenib, as a single agent and in combination with azacitidine, demonstrated “favorable safety and clinical activity” in patients with IDH1-mutated AML, according to results from a phase I study. (Ref. Watts JM, Baer MR, Yang J, et al. Olutasidenib (FT-2102), an IDH1m inhibitor as a single agent or in combination with azacitidine, induces deep clinical responses with mutation clearance in patients with acute myeloid leukemia treated in a phase 1 dose escalation and expansion study. Abstract #231. Presented at the 2019 ASH Annual Meeting, December 7, 2019; Orlando, FL)

Oral Azacitidine Maintenance Improves Survival in Transplant-Ineligible AML: treatment with CC-486, an oral formulation of the hypomethylating agent azacitidine, improved overall survival and relapse-free survival when used as maintenance therapy in patients with AML who were in remission after induction chemotherapy. (Ref. Wei AH, Döhner H, Pocock C, et al. The QUAZAR AML-001 Maintenance Trial: Results of a phase III international, randomized, double-blind, placebo-controlled study of CC-486 (oral formulation of azacitidine) in patients with acute myeloid leukemia (AML) in first remission. Abstract #LBA-3. Presented at the 2019 ASH Annual Meeting, December 10, 2019; Orlando, FL.)

One year of maintenance therapy with brief monthly courses of intravenous decitabine was associated with improved overall survival among older patients with AML who had responded favorably to intensive induction therapy. The findings appear to support the use of maintenance therapy in eligible patients but need to be confirmed in a larger trial. (Ref. Foran JM, Sun Z, Claxton DF, et al. Maintenance decitabine (DAC) improves disease-free (DFS) and overall survival (OS) after intensive therapy for acute myeloid leukemia (AML) in older adults, particularly in FLT3-ITD-negative patients: ECOG-ACRIN (E-A) E2906 randomized study. Abstract 115. Presented at the 2019 American Society of Hematology Annual Meeting, December 7, 2019; Orlando, FL.)

Achievement of MRD Negativity Predicts Favorable Prognosis in RUNX1-RUNX1T1+AML. (Ref. Rücker FG, Agrawal M, Corbacioglu A, et al. Measurable residual disease monitoring in acute myeloid leukemia with t(8;21)(q22;q22.1): results from the AML Study Group. Blood. 2019;134:1608-18)


Early-Phase Study Shows Promising Response Rates With Venetoclax Plus Navitoclax in ALL: nearly half of patients with relapsed/refractory ALL had a complete response after treatment with a combination of venetoclax and navitoclax, according to findings from a phase I study. While nearly all patients experienced at least one grade 3/4 adverse event, there was no unexpected toxicity with this combination. (Ref. Lacayo NJ, Pullarkat VA, Stock W, et al. Safety and efficacy of venetoclax in combination with navitoclax in adult and pediatric relapsed/refractory acute lymphoblastic leukemia and lymphoblastic lymphoma. Abstract #285. Presented at the 2019 ASH Annual Meeting, December 8, 2019; Orlando, FL.)

Compared with standard chemotherapy, blinatumomab as consolidation prior to hematopoietic cell transplantation (HCT) is associated with fewer severe toxicities, higher response rates, and longer survival in children and young adults with high-risk relapse of B-cell acute lymphocytic leukemia (B-ALL). (Ref. Brown PA, Ji L, Xu X, et al. A randomized phase 3 trial of blinatumomab vs. chemotherapy as postreinduction therapy in high and intermediate risk (HR/IR) first relapse of B-acute lymphoblastic leukemia (B-ALL) in children and adolescents/young adults (AYAs) demonstrates superior efficacy and tolerability of blinatumomab: a report from Children’s Oncology Group Study AALL1331. Abstract #LBA-1. Presented at the 2019 ASH Annual Meeting, December 10, 2019; Orlando, FL.)

In patients with relapsed/refractory B-cell precursor ALL who are treated with blinatumomab, achieving minimal residual disease was associated with improved overall survival and relapse-free survival.  The study is however limited by the highly heterogenous patient population, as well as the open-label, single-arm design and there is the need for a more standardized approaches and a follow-up treatment to avoid relapse in patients without a transplant option. (Ref. Gôkbuget N, Kantarjian HM, Brüggemann M, et al. Molecular response with blinatumomab in relapsed/refractory B-cell precursor acute lymphoblastic leukemia. Blood Adv. 2019;3:3033-7)

Early intensification of intrathecal chemotherapy reduces risk of relapse in pediatric ALL. However, higher doses of PEG-asparaginase, another therapy-intensification strategy evaluated in the trial, failed to improve patient outcomes compared with standard doses. (Ref. Jeha S, Pei D, Choi J, et al. Improved CNS control of childhood acute lymphoblastic leukemia without cranial irradiation: St Jude Total Therapy Study 16. J Clin Oncol. 2019;37:3377-91)

February 2020

Treatment with the bispecific CD19/CD3 antibody blinatumomab induced molecular remissions in most infants with persistent measurable residual disease–positive ALL, according to results from a small study. These findings suggest that wider application of blinatumomab can improve cure rates and reduce toxicity for many infants with ALL. (Ref. Clesham K, Rao VN, Bartram J, et al. Blinatumomab for infant acute lymphoblastic leukaemia. Blood. 2020 February 10)

March 2020

Aveo and Biodesix have decided to stop all trials of their hepatocyte growth factor inhibitory antibody ficlatuzumab for AML. The companies have halted the follow-up phase II CyFi-2 study, which was comparing high-dose cytarabine with or without ficlatuzumab with high-dose cytarabine alone in patients with relapsed or refractory AML. (Sources: Aveo press release, March 27, 2020; Fierce Biotech, March 30, 2020)

Genetic risk groups defined by the 2017 European LeukemiaNet recommendations may reliably predict prognosis in patients with AML and internal tandem duplications of FLT3, according to study findings. The study, which analyzed patients enrolled in the randomized RATIFY trial, also verifies the survival benefit associated with protein kinase inhibitor midostaurin in these patients and across all three risk groups included in the 2017 ELN. (Ref. Döhner K, Thiede C, Jahn N, et al. Impact of NPM1/FLT3-ITD genotypes defined by the 2017 European LeukemiaNet in patients with acute myeloid leukemia. Blood. 2020;135:371-380)

Treatment with venetoclax plus low-dose cytarabine (LDAC)  led to greater improvements in remission and overall survival, compared with LDAC alone, in patients with AML who are ineligible for intensive chemotherapy because of advanced age or comorbidities, according to a study published. This therapy combination is also associated with a favorable safety profile, which clinicians may find reassuring, given that the increased risk of treatment-related toxicity associated with intensive chemotherapy often precludes its use in older patients. (Ref. Wei AH, Montesinos P, Ivanov V, et al. Venetoclax plus LDAC for patients with untreated AML ineligible for intensive chemotherapy: phase 3 randomized placebo-controlled trial. Blood. 2020 March 27). 

In a small phase I study of children and young adults with relapsed or refractory AML, venetoclax plus cytarabine chemotherapy, with or without idarubicin, was safe and associated with a relatively high response rate. These findings offer first-time evidence for the potential combined use of BCL2 inhibition and intensive chemotherapy in pediatric patients with AML. (Ref. Karol SE, Alexander TB, Budhraja A, et al. Venetoclax in combination with cytarabine with or without idarubicin in children with relapsed or refractory acute myeloid leukaemia: a phase 1, dose-escalation study. Lancet Oncol. 2020;21:551-560)

April 2020

The FDA has accepted the Investigational New Drug application of CD19-targeting chimeric antigen receptor (CAR) T-cell therapy AUTO1 for the treatment of adults with ALL. AUTO1 is a “fast-off” CAR-T cell therapy designed to minimize excessive activation and associated cytokine release, which may reduce toxicity. It also claims to reduce T cell exhaustion and enhance engraftment. The cell product is also being evaluated in a phase I study as a treatment for pediatric ALL.  (Source: Autolus Therapeutics press release, April 16, 2020)

The FDA has granted orphan drug designation to MT-401, an allogeneic T-cell therapy for the treatment of AML. MT-401, from Marker Therapeutics, is an investigational, multi-tumor-associated antigen-specific T-cell therapy. The FDA’s designation clears the drug to begin a phase II clinical trial of patients with AML after allogeneic stem cell transplantation. (Source: Marker Therapeutics press release, April 29, 2020)

Antithrombin replacement and heparin prophylaxis was not entirely effective for the prevention of venous thromboembolism in adult patients with ALL who received L-asparaginase (L-ASP), according to a study. (Ref. Orvain C, Balsat M, Tavernier E, et al. Thromboembolism prophylaxis in adult patients with acute lymphoblastic leukemia treated in the GRAALL-2005 study. 2020 Apr 22. Blood)

May 2020

The FDA granted priority review status to CC-486 (Oral Azacitidine) for maintenance treatment of adult patients with AML who achieved complete remission (CR) or CR with incomplete blood count recovery after induction therapy with or without consolidation treatment and who are ineligible for hematopoietic cell transplantation. (Source: Bristol-Myers Squibb press release, May 1, 2020)

June 2020


The anti-TIM-3 checkpoint inhibitor MBG453, when added to decitabine or azacitidine, was associated with antileukemic activity and durable response rates in patients with higher-risk MDS and AML, according to a study. MBG453 is a monoclonal antibody that targets TIM-3, a key factor in tumor tolerance and leukemic stem cell preservation. TIM-3 is expressed on leukemic stem cells and blasts, but not on normal hematopoietic stem cells, making it a promising target in MDS/AML. (Ref. Borate U, Esteve J, Porkka K, et al. Anti-TIM-3 antibody MBG453 in combination with hypomethylating agents (HMAS) in patients (PTS) with high-risk myelodysplastic syndrome (HR-MDS) and acute myeloid leukemia (AML): A phase I study. Abstract S185. Presented as part of EHA25 Virtual, June 12, 2020)

A combination of the hypomethylating agent azacitidine and the small-molecule BCL2 inhibitor venetoclax was associated with a 34% reduction in the risk of death, as well as higher response rates, compared with azacitidine alone in a treatment-naïve, predominantly elderly patient population with AML who were not considered candidates for intensive therapy. These findings indicate that the combination approach improves on azacitidine or decitabine monotherapy – currently widely used for older or frailer patients. (Ref. DiNardo C, Jonas B, Pullarkat V, et al. A randomized, double-blind, placebo-controlled study of venetoclax with azacitidine vs azacitidine in treatment-naïve patients with acute myeloid leukemia ineligible for intensives therapy-Viale-A. Abstract LB2601. Presented as part of EHA25 Virtual, June 13, 2020)

For older and unfit patients with AML, venetoclax plus hypomethylating agents (HMAs) have been established as a standard of care and have demonstrated improved survival compared with HMAs alone, but it is unknown how this approach compares with intensive chemotherapy in “fitter” patients. In results from a study, researchers suggested that venetoclax plus decitabine improves outcomes compared with intensive chemotherapy, particularly in patients considered at high risk for treatment-related mortality. (Ref. Maiti A, DiNardo CD, Ravandi F, et al. 10-Day decitabine and venetoclax (DEC10-VEN) vs. intensive chemotherapy (IC) in acute myeloid leukemia (AML): a propensity score matched analysis stratified by risk of treatment-related mortality. Abstract S141. Presented as part of EHA25 Virtual; July 12, 2020)


The anti-CD7 chimeric antigen receptor (CAR) T-cell therapy TruUCAR GC027 demonstrated promising efficacy in treating adults with relapsed or refractory T-cell ALL, according to findings from a first-in-human study. T-ALL comprises about 20% to 25% of cases of adult ALL and CD7 is present on more than 95% of T-ALL samples. However, the development of CAR T-cell therapy targeting CD7 has been limited in this setting by CD7 expression on normal T cells and potential contamination by T-ALL cells. (Ref. Wang X, Li S, Gao L, et al. First-in-human, universal anti-CD7 CAR-T therapy for relapsed and refractory T-cell acute lymphoblastic leukemia (R/R T-ALL). Abstract S115. Presented as part of EHA25 Virtual, June 12, 2020)

July 2020

Older patients with AML who undergo post-remission therapy may be at risk of poor survival if they present with impaired physical function and increased depressive symptoms at time of post-remission evaluation, according to a study. The study demonstrates the value of geriatric assessment to strengthen risk stratification and identify vulnerabilities associated with AML in older adults. (Ref. Saad M, Loh KP, Tooze JA, et al. Geriatric assessment and survival among older adults receiving post-remission therapy for acute myeloid leukemia. Blood. 2020 July 22)

September 2020

The FDA has extended the indication of gemtuzumab ozogamicin to include pediatric patients aged 1 month or older with newly diagnosed CD33-positive AML. The treatment was previously approved for adults with newly diagnosed CD33-positive AML and patients aged 2 years and older with relapsed/refractory disease. (Sources: FDA press release, September 1, 2017; FDA press release, June 16, 2020)

The FDA has approved azacitidine tablets, formerly known as CC-486, for the continued treatment of adults with AML who achieved first complete remission or complete remission with incomplete blood count recovery following induction chemotherapy and who are ineligible for intensive curative therapy. (Sources: FDA press release, September 1, 2020; BMS press release, September 1, 2020)

For patients with AML and an FLT3-ITD mutation, maintenance treatment with the multitargeted TKI sorafenib significantly prolonged relapse-free survival after allogeneic hematopoietic cell transplantation, compared with placebo, according to results of the German-Austrian phase II SORMAIN trial. (Ref. Burchert A, Bug G, Fritz LV, et al. Sorafenib maintenance after allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia with FLT3–internal tandem duplication mutation (SORMAIN). J Clin Oncol. 2020;38:2993-3002)

October 2020

Venetoclax in combination with azacitidine, decitabine, or low-dose cytarabine (LDAC) has been approved for the treatment of adults with newly diagnosed AML who are age 75 years or older, or who are ineligible for intensive induction chemotherapy. (Source: Abbvie press release, October 16, 2020)

December 2020

The addition of the BCL2 inhibitor venetoclax (alternating with the hypomethylating agent azacitidine) to a low-intensity backbone combination of cladribine with low-dose cytarabine  led to high rates of durable remissions and measurable residual disease negativity in older patients with newly diagnosed AML. (Ref. Kadia TM, Borthakur G, Pemmaraju N, et al. Phase II study of venetoclax added to cladribine + low dose AraC (LDAC) alternating with 5-azacytidine demonstrates high rates of minimal residual disease (MRD) negative complete remissions (CR) and excellent tolerability in older patients with newly diagnosed acute myeloid leukemia (AML). Abstract #25. Presented at the 2020 American Society of Hematology Annual Meeting, December 5, 2020)