Suboptimal persistence with IV and SC HMA therapy may limit its clinical benefits1-3
Significant rates of HMA discontinuation1,2
~58% of patients with AML showed early HMA discontinuation1*†
<45% of patients with MDS showed early HMA discontinuation2*‡
*Defined as the completion of <4 HMA cycles.1,2
†In a retrospective US claims/registry analysis of 2263 older adults (age 66 to 99) who received an AML diagnosis from 2005 to 2015 and started HMA treatment (azacitidine or decitabine) in the first-line setting within 6 months.1
‡Based on 4 studies published between 2014 and 2021, identified through a retrospective US analysis of articles published from 2008 to 2021, that described real-world treatment persistence among patients with higher-risk MDS receiving IV or SC HMA therapies.2
Barriers to persistence
While the reasons for nonadherence vary, they may include:
Logistical and administrational challenges2,3
Distress and discomfort associated with parenteral administration2,3
Extensive travel and treatment time2,4
These barriers can lead to discontinuation of HMA therapy, which may be associated with:
Rapid disease progression2,5
Poor prognosis2,5
Higher healthcare resource use2,6
Without staying on treatment for the recommended number of cycles, patients may not experience the potential clinical benefits of HMA therapy.3
Patient preference
Patients with AML or MDS may prefer oral HMA options.3,7,8
References: 1. Zeidan AM, Wang R, Wang X, et al. Clinical outcomes of older patients with AML receiving hypomethylating agents: a large population-based study in the United States. Blood Adv. 2020;4(10):2192-2201.
2. Zeidan AM, Salimi T, Epstein RS. Real-world use and outcomes of hypomethylating agent therapy in higher-risk myelodysplastic syndromes: why are we not achieving the promise of clinical trials? Future Oncol. 2021;17(36):5163-5175. 3. Haumschild R, Kennerly-Shah J, Barbarotta L, Zeidan AM. Clinical activity, pharmacokinetics, and pharmacodynamics of oral hypomethylating agents for myelodysplastic syndromes/neoplasms and acute myeloid leukemia: a multidisciplinary review. J Oncol Pharm Pract. 2024;30(4):721-736. 4. Jensen CE, Heiling HM, Beke KE, et al. Time spent at home among older adults with acute myeloid leukemia receiving azacitidine- or venetoclax-based regimens. Haematologica. 2022;108(4):1006-1014. 5. Cabrero M, Jabbour E, Ravandi F, et al. Discontinuation of hypomethylating agent therapy in patients with myelodysplastic syndromes or acute myelogenous leukemia in complete remission or partial response: retrospective analysis of survival after long-term follow-up. Leuk Res. 2015;39(5):520-524. 6. Cheng WY, Satija A, Cheung HC, et al. Persistence to hypomethylating agents and clinical and economic outcomes among patients with myelodysplastic syndromes. Hematology. 2021;26(1):261-270. 7. Delmas A, Batchelder L, Arora I, et al. Exploring preferences of different modes of administration of hypomethylating agent treatments among patients with acute myeloid leukemia. Front Oncol. 2023;13:1160966. 8. Zeidan AM, Tsai J-H, Karimi M, et al. Patient preferences for benefits, risks, and administration route of hypomethylating agents in myelodysplastic syndromes. Clin Lymphoma Myeloma Leuk. 2022;22(9):e853-e866.
IMPORTANT SAFETY INFORMATION
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Myelosuppression INQOVI as Monotherapy for MDS or CMML
In patients with MDS or CMML, INQOVI can cause severe myelosuppression, including fatal adverse reactions. Based on laboratory values, new or worsening thrombocytopenia occurred in 82% of patients, with Grade 3 or 4 occurring in 76%. Neutropenia occurred in 73% of patients, with Grade 3 or 4 occurring in 71%. Anemia occurred in 71% of patients, with Grade 3 or 4 occurring in 55%. Febrile neutropenia occurred in 33% of patients, with Grade 3 or 4 occurring in 32%. Thrombocytopenia, neutropenia, anemia, and febrile neutropenia are the most frequent cause of INQOVI dose reduction or interruption, occurring in 36% of patients. Permanent discontinuation due to myelosuppression (febrile neutropenia) occurred in 1% of patients. Myelosuppression and worsening neutropenia may occur more frequently in the first or second treatment cycles and may not necessarily indicate progression of underlying MDS.
Fatal and serious infectious complications can occur with INQOVI. Pneumonia occurred in 21% of patients, with Grade 3 or 4 occurring in 15%. Sepsis occurred in 14% of patients, with Grade 3 or 4 occurring in 11%. Fatal pneumonia occurred in 1% of patients, fatal sepsis in 1%, and fatal septic shock in 1%.
Obtain complete blood cell counts prior to initiation of INQOVI, prior to each cycle, and as clinically indicated to monitor response and toxicity. Administer growth factors and anti‑infective therapies for treatment or prophylaxis as appropriate. Delay the next cycle and resume at the same or reduced dose as recommended.
INQOVI in Combination with Venetoclax for AML
In patients with AML, INQOVI can cause severe myelosuppression, including fatal adverse reactions, when given in combination with venetoclax. Based on laboratory values in Study ASTX727-07, Phase 2 new or worsening thrombocytopenia occurred in 70% of patients, with Grade 3 or 4 occurring in 69%. Neutropenia occurred in 48% of patients, with Grade 3 or 4 occurring in 48%. Anemia occurred in 54% of patients, with Grade 3 or 4 occurring in 50%. Febrile neutropenia occurred in 52% of patients, with Grade 3 or 4 occurring in 52%. Thrombocytopenia, neutropenia, anemia, and febrile neutropenia were a frequent cause of INQOVI and/or venetoclax dose reduction or interruption. Dose reductions of INQOVI due to neutropenia and thrombocytopenia occurred in 4% and 1% of patients, respectively. Dose interruptions of INQOVI due to neutropenia, febrile neutropenia, thrombocytopenia, and anemia occurred in 40%, 11%, 8%, and 2% of patients, respectively.
Fatal and serious infectious complications can occur during treatment with INQOVI and venetoclax. Pneumonia occurred in 25% of patients, with Grade 3 or 4 occurring in 20%. Sepsis occurred in 28% of patients, with Grade 3 or 4 occurring in 18%. Fatal pneumonia occurred in 2% of patients and fatal sepsis in 8%.
Obtain complete blood cell counts prior to initiation of INQOVI with venetoclax, prior to each cycle, and as clinically indicated to monitor response and toxicity. Administer growth factors and anti-infective therapies for treatment or prophylaxis as appropriate. Delay the next cycle and resume at the same or reduced dose as recommended.
Embryo-Fetal Toxicity
Advise patients of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with INQOVI and for 6 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with INQOVI and for 3 months after the last dose.
ADVERSE REACTIONS
INQOVI as Monotherapy for MDS or CMML
Serious adverse reactions occurred in 68% of patients who received INQOVI. Serious adverse reactions in >5% of patients included febrile neutropenia (30%), pneumonia (14%), and sepsis (13%). Fatal adverse reactions occurred in 6% of patients. These included sepsis (1%), septic shock (1%), pneumonia (1%), respiratory failure (1%), and one case each of cerebral hemorrhage and sudden death.
The most common adverse reactions (≥20%) were fatigue (55%), constipation (44%), hemorrhage (43%), myalgia (42%), mucositis (41%), arthralgia (40%), nausea (40%), dyspnea (38%), diarrhea (37%), rash (33%), dizziness (33%), febrile neutropenia (33%), edema (30%), headache (30%), cough (28%), decreased appetite (24%), upper respiratory tract infection (23%), pneumonia (21%), and transaminase increased (21%). The most common Grade 3 or 4 laboratory abnormalities (≥50%) were leukocytes decreased (81%), platelet count decreased (76%), neutrophil count decreased (71%), and hemoglobin decreased (55%).
INQOVI in Combination with Venetoclax for AML
Serious adverse reactions occurred in 82% of patients who received INQOVI+VEN. Serious adverse reactions in >5% of patients included febrile neutropenia (31%), sepsis (22%), pneumonia (15%), infection (bacterial/viral) (10%), hemorrhage (9%), and dyspnea (6%). Fatal adverse reactions occurred in 8% of patients who received INQOVI+VEN. These included sepsis (5%), dyspnea (2%), myocardial infarction (1%), hemolytic anemia (1%), and tumor lysis syndrome (1%).
The most common adverse reactions (≥20%) were neutropenia (60%), febrile neutropenia (52%), thrombocytopenia (52%), hemorrhage (42%), anemia (41%), infection (bacterial/viral) (40%), diarrhea (38%), fatigue (36%), mucositis (36%), constipation (36%), arthralgia (35%), decreased appetite (31%), edema (31%), nausea (31%), dyspnea (30%), white blood cell count decreased (28%), sepsis (28%), pneumonia (25%), rash (25%), transaminitis (24%), myalgia (23%), arrhythmia (21%), and abdominal pain (21%). The most common Grade 3 or 4 laboratory abnormalities (≥20%) were decreased leukocytes (91%), decreased lymphocytes (81%), decreased platelets (69%), decreased hemoglobin (50%), and decreased neutrophils (48%).
USE IN SPECIFIC POPULATIONS
Lactation
Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment with INQOVI and for 2 weeks after the last dose.
Renal Impairment
No dosage modification of INQOVI is recommended for patients with mild or moderate renal impairment (creatinine clearance [CLcr] of 30 to 89 mL/min based on Cockcroft-Gault). Due to the potential for increased adverse reactions, monitor patients with moderate renal impairment (CLcr 30 to 59 mL/min) frequently for adverse reactions. INQOVI has not been studied in patients with severe renal impairment (CLcr 15 to 29 mL/min) or end-stage renal disease (ESRD: CLcr <15 mL/min).
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