Outcomes of Relapsed or Refractory Acute Myeloid Leukemia after Frontline Hypomethylating Agent with Venetoclax Regimens

Maiti, Abhishek; Rausch, Caitlin R.; Cortés, Jorge E.; Pemmaraju, Naveen; Daver, Naval; Ravandi, Farhad; Borthakur, Gautam; Naqvi, Kiran; Ohanian, Maro; Alvarado, Yesid; Benton, Christopher B.; Kadia, Tapan M.; Takahashi, Koichi; Yılmaz, Musa; Jain, Nitin; Kornblau, Steven M.; Bravo, Guillermo Montalbán; Sasaki, Koji; Andreeff, Michael; Bose, Prithviraj; Ferrajoli, Alessandra; Issa, Ghayas C.; Masárová, Lucia; Rytting, Michael; Thompson, Philip A.; Wang, Sa A.; Konoplev, Sergej; Chen, Zhining; Goswami, Maitrayee; Maduike, Rita; Guerrero, Julio A; Zhang, Qi; Cavazos, Antonio; Ma, Helen; Bivins, Carol; Wade, Allison; Adewale, Shadiat L; Tse, Susan; Thomas, Robin; Vaughan, Kenneth; Pierce, Sherry; Ning, Jing; Qiao, Wei; Welch, John S.; Kantarjian, Hagop M.; Konopleva, Marina; DiNardo, Courtney D.

doi:10.1182/blood-2019-128909

Cited by 29 publications

(50 citation statements)

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“…39,40 The approval was based on a phase 1/2 trial. 29 Here, enasidenib monotherapy achieved an ORR of 40.3%, with a median dura tion of response of 5.8 months and a median OS of 9.3 months in R/R IDH2-mutated AML patients. 40 GO also received approval by the FDA (not the EMA) for R/R patients with CD33 + AML and can be added to inten sive ther apy.…”

Section: Treatment Of Aml In Relapsementioning

confidence: 79%

“…Unfortunately, a ret ro spec tive anal y sis sug gests that once patients become unre spon sive to HMA/VEN the prog no sis is very poor. 29 This might be related to the acqui si tion of high-risk cytoge netic and molec u lar fea tures (eg, muta tions in TP53, N/KRAS, and/or KIT). 29 For patients who are older but lack comorbidities, the ques tion arises as to whether inten sive ther apy or HMA/VEN treat ments are the wiser treat ment choice.…”

Section: Nonintensive Ther Apy With Novel Agentsmentioning

confidence: 99%

“…29 This might be related to the acqui si tion of high-risk cytoge netic and molec u lar fea tures (eg, muta tions in TP53, N/KRAS, and/or KIT). 29 For patients who are older but lack comorbidities, the ques tion arises as to whether inten sive ther apy or HMA/VEN treat ments are the wiser treat ment choice. To date, there is no ran dom ized trial com par ing inten sive che mo ther apy with HMA-VEN head-to-head.…”

Section: Nonintensive Ther Apy With Novel Agentsmentioning

confidence: 99%

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What to use to treat AML: the role of emerging therapies

Thol

2021

Hematology

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The development and approval of novel substances have resulted in substantial improvements in the treatment of acute myeloid leukemia (AML). In the current era of novel treatment options, genetic and molecular testing at the time of diagnosis and relapse becomes increasingly relevant. Midostaurin in combination with intensive chemotherapy is the standard of care as upfront therapy in younger AML patients with mutated fms-related tyrosine kinase 3 (FLT3). Gilteritinib, a second- generation FLT3 inhibitor, represents a key drug for relapsed/refractory (R/R) FLT3-mutated AML patients. Targeted therapy has also been developed for patients with mutated isocitrate dehydrogenase 1 (IDH1) and IDH2. The US Food and Drug Administration (FDA) approved ivosidenib as a monotherapy for newly diagnosed older adult IDH1-mutated patients and enasidenib for R/R IDH2-mutated AML patients. CPX-351, a liposomal formulation of daunorubicin and cytarabine, has become an important upfront treatment strategy for fit patients with therapy-related AML or AML with myelodysplasia-related changes that are generally challenging to treat. The antibody drug conjugate gemtuzumab ozogamicin was approved in combination with intensive therapy for patients with newly diagnosed (FDA/European Medicines Agency [EMA]) as well as R/R CD33+ AML. The combination of venetoclax, an oral selective B-cell leukemia/lymphoma-2 inhibitor, with hypomethylating agents or low-dose AraC (LDAC) has changed the treatment landscape and prognosis for older adult patients very favorably. The addition of glasdegib, a small-molecule hedgehog inhibitor, to LDAC is another example of novel options in older patients. Further substances have shown promising results in early clinical trials.

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Section: Treatment Of Aml In Relapsementioning

confidence: 79%

Section: Nonintensive Ther Apy With Novel Agentsmentioning

confidence: 99%

Section: Nonintensive Ther Apy With Novel Agentsmentioning

confidence: 99%

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What to use to treat AML: the role of emerging therapies

Thol

2021

Hematology

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“…After patients attain remission with VENbased therapy, we periodically monitor the ongoing response using bone marrow biopsies performed every 3-6 months, and we routinely test for MRD to identify early relapse. Patients relapsing after VEN-based therapy have a poor prognosis, as demonstrated by Maiti et al, 41 and such patients should be referred for clinical trials.…”

Section: Duration Of Venetoclax-based Therapy and Allohct After Ven-hmamentioning

confidence: 99%

Venetoclax-containing regimens in acute myeloid leukemia

Aldoss

Pullarkat

Stein

2021

Therapeutic Advances in Hematology

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Venetoclax in combination with hypomethylating agents (HMAs) or low-dose cytarabine (LDAC) has demonstrated exceptional activity in elderly and unfit patients with newly diagnosed acute myeloid leukemia (AML). Notably, the safety profile of venetoclax-based induction regimens was favorable, with a low rate of early treatment-related mortality, even in frail study participants. Thus, the introduction of venetoclax has transformed the landscape of AML therapy in elderly patients. Given these promising results, venetoclax in combination with other agents is now being studied as a frontline therapy in younger patients with AML, as well as in relapsed/refractory AML patients. Here, we review clinical data for venetoclax-based therapy in AML, both from prospective as well as retrospective studies, and highlight ongoing novel studies of venetoclax-containing regimens and discuss future research directions.

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“…However, although the majority of patients will respond to this new standard regimen, relapses still occur with more resistant clones. Those who lose their responses after HMA−venetoclax combinations will have a dismal outcome and a median OS of 2.4 months regardless of salvage treatment used [9]. Strategies to improve further the long-term outcomes of venetoclax-based combinations and reach a potential cure for older AML adults are much needed.…”

mentioning

confidence: 99%

Exciting times ahead for older patients with acute myeloid leukemia: azacitidine and venetoclax followed by allogeneic hematopoietic cell transplantation

Bazarbachi

2021

Bone Marrow Transplant

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Outcomes of Relapsed or Refractory Acute Myeloid Leukemia after Frontline Hypomethylating Agent with Venetoclax Regimens

Cited by 29 publications

References 0 publications

What to use to treat AML: the role of emerging therapies

What to use to treat AML: the role of emerging therapies

Venetoclax-containing regimens in acute myeloid leukemia

Exciting times ahead for older patients with acute myeloid leukemia: azacitidine and venetoclax followed by allogeneic hematopoietic cell transplantation

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