Not Very Impressed
Why use this when I can use VEN/ASA?
Remind your customers that acute leukemias with a KMT2A rearrangement are aggressive diseases associated with a very poor prognosis and high rates of resistance and relapse. 1,2
For adult patients with AML with a KMT2A rearrangement, up to 82% relapse within the first year following second-line therapy, and only 9% achieve CR or CRi following third-line or later therapy?
In the AUGMENT-101 clinical trial, note how REV was studied in a heavily pretreated patient population.
We treat RR AML but, I’m not sure we’ve identified a KMT2A abnormality?
KMT2A translocations are a type of KMT2A gene rearrangement (or KMT2Ar), which may also be referred to as mixed-lineage leukemia rearranged (or MLLr). KMT2A rearrangements can occur across multiple age groups in AML, ALL, and mixed-phenotype acute leukemia (MPAL).* While KMTZA rearrangements are detected more frequently in infant cases, up to 10% of adults with ALL or AML test positive for KMT2Ar. I-3
Approximately 95% of patients with KMT2Ar acute leukemia have a KMT2A translocation, a type of rearrangement that occurs when part of one chromosome breaks and fuses to a different chromosome.
What percentage of pts in your trial experienced DS?
Discuss the data from the Prescribing Information, pointing out that 29% of patients (39/135) experienced differentiation syndrome, with a median time to onset of 10 days (range: 3-41 days).
What’s the starting dose for a 90.lbs patient not on a strong CYP3A4 inhibitor?
Explain how the starting dose for patients weighing more than 40 kg without a strong CYP3A4 inhibitor is 270 mg orally twice daily. This dosage would require patients to be prescribed both the 160-mg and 110-mg tablets. If the patient is on a strong CYP3A4 inhibitor, then the starting dose is 160 mg orally twice daily.
Close by reminding customers that Revuforj offers the convenience of an oral, targeted therapy that patients can take at home.
The Von Trapp family, whose escape from Austria during WW11 was made famous in the 1965 musical “The Sound of Music,” moved to which New England state upon feeling Europe?
Hint: This location was chosen for its Alpine landscape, similar to what they left behind.
Vermont
Why wasn’t ORR your primary endpoint?
When discussing overall response rate and/or composite complete remission, it's important to note that secondary endpoints were predefined but were not powered in the statistical plan at the time of the interim analysis.
Which tests detect KMT2Ar?
You can inform them that KMT2Ar, including translocations, can be detected by standard cytogenetic testing, such as karyotyping and fluorescence in situ hybridization (FISH).
Remind them how it's important to request and confirm with their pathologist that KMT2A rearrangements are included when testing at both diagnosis and relapse.
KMT2A rearrangements may show up as "KMT2Ar" or "MLLr" located at "11q23."
How do you recommend we manage DS?
Inform customers that if differentiation syndrome is suspected, immediately initiate treatment with systemic corticosteroids (eg, dexamethasone 10 mg intravenously every 12 hours in adults or dexamethasone 0.25 mg/kg/dose intravenously every 12 hours in pediatric patients weighing less than 40 kg) for a minimum of 3 days and until resolution of signs and symptoms.
Institute supportive measures and hemodynamic monitoring until improvement.
Interrupt Revuforj if severe signs and/or symptoms persist for more than 48 hours after initiation of systemic corticosteroids, or earlier if life-threatening symptoms occur such as pulmonary symptoms requiring ventilator support. Restart steroids promptly if differentiation syndrome recurs after tapering corticosteroids.
"Can I use Revuforj in my AML patients with an NPM1 mutation?"
Revuforj is approved for the treatment of relapsed or refractory acute leukemia with a KMTZA translocation in adult and pediatric patients 1 year and older. There are multiple clinical trials ongoing for Revuforj, but the safety and efficacy in those populations have not been established.
If you have any specific questions regarding use in patients with NPM1m AML, I would be happy to submit a medical information request form (MIRF).
ACTION: If your customers have additional questions, you may offer to complete/submit a medical information request on their behalf.
In 1939 which New England state passed legislation to make it illegal to put tomatoes in clam chowder?
Maine
Why is the CR + CRh Rate so low?
In the AUGMENT-101 clinical trial, note how Revuforj was studied in a heavily pretreated patient population with challenging disease characteristics
Median of 2 previous regimens (range: 1-11)
26% had relapsed at least twice
44% had received at least 1 hematopoietic stem cell transplant (HSCT)
Remind your customers that acute leukemias with a KMT2A rearrangement are aggressive diseases associated with a very poor prognosis and high rates of resistance and relapse.
For adult patients with AML with a KMTZA rearrangement, up to 82% relapse within the first year following second-line therapy, and only 9% achieve CR or CRi following third-line or later therapy.
Can I use Revuforj in combo with other treatments?
In the AUGMENT-101 clinical trial, Revuforj was studied as a single agent and the approval is based on singe-agent data. If you have any specific questions regarding combination use, I would be happy to submit a medical information request form (MIRF)
"I'm concerned about QTc prolongation, especially in patients who have existing cardiac issues."
Share that you understand how QTc prolongation can be concerning as it is a serious adverse reaction.
Discuss the data from the label, pointing out that QTc interval prolongation occurred in 29% of patients (39/135). QTc interval prolongation was Grade 3 in 12% of patients, and Revuforj dose reduction was required for 5% of patients.
Inform customers that they should monitor for QTc interval prolongation and manage any abnormalities promptly. Per the Prescribing Information, blood counts, electrolytes, and liver enzymes should be assessed prior to the initiation of Revufori and monthly thereafter. Perform an electrocardiogram (ECG) prior to the initiation of Revuforj, at least once a week for the first 4 weeks, and at least monthly thereafter.
Remind customers to correct electrolyte abnormalities, including hypokalemia and hypomagnesemia, prior to treatment with Revuforj. It's also important to note that Revuforj should not be initiated in patients with QTcF >450 msec.
In patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval, more frequent monitoring may be necessary.
DAILY DOUBLE!!!!!
The very first hamburger was created in which New England state back in 1895?
Connecticut
Which New England state operates out of the oldest State Capital Building in the country and boasts the record for the world’s highest wind speeds recorded at ground level on April 12th, 1934?
New Hampshire
Oh, another menin inhibitor, like Zifto right?
Remind customers that Revuforj offers a clinical benefit to patients as the only FDA-approved targeted treatment for relapsed or refractory acute leukemias with a KMT2A translocation.
I‘m confused, What’s the difference between a translocation and a rearrangement?
A gene rearrangement refers to any change to the structure of a chromosome, including translocations, deletions, insertions, and tandem duplications. A translocation is a type of rearrangement that occurs when part of one chromosome breaks and fuses to a different chromosome. Approximately 95% of patients with acute leukemia who have a KMT2A gene rearrangement (KMT2Ar) have a KMT2A translocation.1
Revuforj is indicated for the treatment of relapsed or refractory acute leukemia with a KMT2A translocation in adult and pediatric patients 1 year and older.?
"I'm concerned about the potential for my patients to develop differentiation syndrome and how to manage it."
Share that you understand how differentiation syndrome can be concerning as it is a serious adverse reaction.
Discuss the data from the Prescribing Information, pointing out that 29% of patients (39/135) experienced differentiation syndrome, with a median time to onset of 10 days (range: 3-41 days).
Mention how treatment interruption was required for 7% of patients and was withdrawn for 1%. It's also important to note that the white blood cell (WBC) count should be reduced to less than 25 Gi/L prior to starting Revuforj.
Inform customers that if differentiation syndrome is suspected, immediately initiate treatment with systemic corticosteroids (eg, dexamethasone 10 mg intravenously every 12 hours in adults or dexamethasone 0.25 mg/kg/dose intravenously every 12 hours in pediatric patients weighing less than 40 kg) for a minimum of 3 days and until resolution of signs and symptoms.
Institute supportive measures and hemodynamic monitoring until improvement.
Interrupt Revuforj if severe signs and/or symptoms persist for more than 48 hours after initiation of systemic corticosteroids, or earlier if life-threatening symptoms occur such as pulmonary symptoms requiring ventilator support. Restart steroids promptly if differentiation syndrome recurs after tapering corticosteroids.
For customers with patients who are taking Revuforj, encourage them to talk with their patients about the importance of always carrying the Differentiation Syndrome Wallet Card with them.
Close by reminding customers that Revuforj offers a clinical benefit to patients as the only FDA-approved targeted treatment for relapsed or refractory acute leukemia with a KMT2A translocation. They should consider the benefits and risks of any treatment to determinA of gat is right for their patients.
"Dosing seems somewhat complicated."
Inform customers the recommended dosage of Revuforj varies by patient weight and concomitant use of strong CYP3A4 inhibitors. Ask them if their patient weighs more than 40 kg (88 lbs.). If so, show them the recommended dosage from the Prescribing Information (Table 1).
Explain how the starting dose for patients weighing more than 40 kg without a strong CYP3A4 inhibitor is 270 mg orally twice daily. This dosage would require patients to be prescribed both the 160-mg and 110-mg tablets. If the patient is on a strong CYP3A4 inhibitor, then the starting dose is 160 mg orally twice daily.
Close by reminding customers that Revuforj offers the convenience of an oral, targeted therapy that patients can take at home.
Which New England State has the oldest U.S. newspaper still being published: Established in 1764?
Connecticut
“The Hartford Courant”
Why is your data in the PI different from the phase 2 data published in the Journal of Clinical Oncology?
The data presented for Revuforj have consistently demonstrated a clinical benefit in patients 1 year and older with relapsed or refractory acute leukemia with a KMT2A translocation.
There may be numerical differences in data presentations depending on study patient populations, timing of data cuts, and data pooling.
The data in the FDA-approved Prescribing Information combine patients from both the phase 1 and phase 2 portions of AUGMENT-101. Data from a prespecified analysis of the phase 2 portion of the clinical trial were published in the Journal of Clinical Oncology. These data are a subset of the label data and are consistent with the pooled population.
ACTION: You may direct the conversation to the Reprint Carrier
Shouldn’t I refer a patient like this to a trial option?
Reiterate that Revuforj is the first and only FDA-approved menin inhibitor that targets relapsed or refractory acute leukemia with a KMT2A translocation.
Revuforj offers the convenience of an oral, targeted therapy that patients can take at home.
Early identification of KMT2A rearrangements is critical given the rapid onset and quick progression of KMT2Ar AML and ALL.5,6 Detecting KMT2Ar, particularly KMT2A translocations, can help determine a specific course of action and identify relapsed/refractory patients who may benefit from a targeted treatment.
DAILY DOUBLE!!!!!
in 1891, Dr. James Naismith invented the great game of what in Springfield, Massachusett?
Basketball
“Based on the recommended dose, I cannot give Revuforj to my pediatric patients."
Reiterate how Revuforj is approved for pediatric patients 1 year and older. Ask your customer whether their patient can swallow tablets.
If the patient is able to swallow the tablets whole, advise them not to cut or chew tablets. For patients who are unable to swallow tablets whole, Revuforj tablets may be crushed and dispersed in water and taken within 2 hours of preparation.
Offer to review the Instructions for Use with your customer.
Encourage customers to have their patients read the FDA-approved patient labeling (Medication Guide) and Instructions for Use.
The term “sideburns” is named after Ambrose Burnside, a former governor of which New England state?
Rhode Island
Also,
In 1678, the country’s first traffic law was created when authorities banned galloping horses on the local streets of Newport, RI.