ASH Clinical News October 2017 | Page 31

CLINICAL NEWS

The study is limited by its small patient population , single-arm design , and limited follow-up .

AbbVie and Genentech , the manufacturers of venetoclax , provided financial support for the study . The authors report financial support from Celgene , Janssen-Cilag , Takeda , Novartis , Amgen , AbbVie , Servier , Merck , and BeiGene .

REFERENCE

Moreau P , Chanan-Khan A , Roberts AW , et al . Promising efficacy and acceptable safety of venetoclax plus bortezomib and dexamethasone in relapsed / refractory MM . Blood . 2017 August 28 . [ Epub ahead of print ]

The hypomethylating agents ( HMAs ) azacitidine and decitabine have been shown to improve survival and / or delay disease progression in patients with higher-risk myelodysplastic syndromes ( MDS ), but outcomes in lower-risk disease have not been as systematically reported . In a randomized study published in Blood , HMAs could be administered in doses lower than what is approved , and are safe and effective in patients with less severe MDS .

Elias Jabbour , MD , from The University of Texas MD Anderson Cancer Center in Houston , and co-authors on behalf of the U . S . MDS Clinical Research Consortium enrolled 113 adult patients ( median age = 70 years ; range = 44-84

ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling :

• Hemorrhage [ see Warnings and Precautions ]

• Cardiotoxicity [ see Warnings and Precautions ]

• Hypersensitivity Reactions [ see Warnings and Precautions ]

• Copper Overload [ see Warnings and Precautions ]

• Tissue Necrosis [ see Warnings and Precautions ]

Clinical Trials Experience Because clinical trials are conducted under widely varying conditions , adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice .

The safety of VYXEOS was determined in a randomized trial for adults with newly-diagnosed t-AML or AML-MRC which included 153 patients treated with VYXEOS and 151 patients treated with a standard combination of cytarabine and daunorubicin ( 7 + 3 ). At study entry , patients were required to have a LVEF of at least 50 % and a prior lifetime cumulative anthracycline exposure less than 368 mg / m 2 daunorubicin ( or equivalent ). On study , the median number of cycles administered was 2 ( range , 1 – 4 cycles ) on the VYXEOS arm and 1 ( range , 1 – 4 cycles ) on the control arm . The median cumulative daunorubicin dose was 189 mg / m 2 ( range , 44 – 337 mg / m 2 ) on the VYXEOS arm and 186 mg / m 2 ( range , 44 – 532 mg / m 2 ) on the control arm .

Nine patients each on the VYXEOS arm ( 6 %) and the control arm ( 6 %) had a fatal adverse reaction on treatment or within 30 days of therapy that was not in the setting of progressive disease . Fatal adverse reactions on the VYXEOS arm included infection , CNS hemorrhage , and respiratory failure . Overall , all-cause day-30 mortality was 6 % in the VYXEOS arm and 11 % in the control arm . During the first 60 days of the study , 14 % ( 21 / 153 ) of patients died in the VYXEOS arm vs . 21 % ( 32 / 151 ) of patients in the 7 + 3 treatment group .

The most common serious adverse reactions ( incidence ≥5 %) on the VYXEOS arm were dyspnea , myocardial toxicity , sepsis , pneumonia , febrile neutropenia , bacteremia and hemorrhage . Adverse reactions led to discontinuation of VYXEOS in 18 % ( 28 / 153 ) of patients , and 13 % ( 20 / 151 ) in the control arm . The adverse reactions leading to discontinuation on the VYXEOS arm included prolonged cytopenias , infection , cardiotoxicity , respiratory failure , hemorrhage ( GI and CNS ), renal insufficiency , colitis , and generalized medical deterioration . The most common adverse reactions ( incidence ≥25 %) in patients on the VYXEOS arm were hemorrhagic events , febrile neutropenia , rash , edema , nausea , mucositis , diarrhea , constipation , musculoskeletal pain , fatigue , abdominal pain , dyspnea , headache , cough , decreased appetite , arrhythmia , pneumonia , bacteremia , chills , sleep disorders , and vomiting . The incidences of common adverse drug reactions during the induction phase in Study 1 are presented in Table 2 .

Table 2 : Common Adverse Reactions ( ≥10 % Incidence in the VYXEOS arm ) During the Induction Phase

All Grades a Grades 3 to 5 a

Adverse Reaction

VYXEOS N = 153 n (%)

7 + 3 N = 151 n (%)

VYXEOS N = 153 n (%)

7 + 3 N = 151 n (%)

Adverse Reaction

VYXEOS N = 153 n (%)

All Grades a

7 + 3 N = 151 n (%)

Grades 3 to 5 a

VYXEOS N = 153 n (%)

7 + 3 N = 151 n (%)

a

Adverse reactions were graded using NCI CTCAE version 3.0 .

During the consolidation phase ( both consolidation cycles pooled ) the two most common adverse reactions on the VYXEOS arm are the same as those during induction , hemorrhagic events and febrile neutropenia . These occurred at lower rates in the pooled consolidation phase ( 43 % and 29 %, respectively ), compared to the induction phase . All of the common adverse reactions ( ≥10 % incidence in the VYXEOS arm ) seen in the pooled consolidation phase were also seen in the induction phase . These occurred at lower incidence in the consolidation phase , with the exception of chills , dizziness and pyrexia , where the incidences were relatively similar across the induction and consolidation cycles .