PATIENTS
WITH RELAPSED/
REFRACTORY
mIDH1 AML
HAVE
A POOR PROGNOSIS
\Hello \Dr\##accLname##,
\I hope all is well. I wanted to send this information about
the poor prognosis for patients with mIDH1 AML and how a treatment may help.Acute myeloid leukemia (AML) is a malignancy characterized by uncontrolled
clonal expansion of myeloblasts in the bone marrow and peripheral blood, most
frequently diagnosed in patients aged 65 to 74 years. The 5-year survival rate for
all patients with AML is 31.7% and drops to 10.7% for patients aged ≥65 years.1-5
Over half (57%) of patients with AML treated with induction therapy die or
have relapsed/refractory AML within 12 months of diagnosis. Patients with
relapsed/refractory AML experience dismal outcomes.2,6
IDH1
GENE MUTATIONS HAVE BEEN REPORTED
IN
6% TO 9% OF PATIENTS
WITH AML
In such a vulnerable patient population, it’s important to test for
IDH1, an identified, actionable mutation with options for targeted
treatment.7-9
Median
Overall Survival (OS) of Patients with
mIDH1
AML
Across Treatment Settings10
 
A median OS of <6 months in the relapsed/
refractory
setting emphasizes the
need
for
therapeutic
options to improve patient
outcomes10
|
|
|
|
REZLIDHIA
INDUCES DURABLE
COMPLETE REMISSIONS
REZLIDHIA is indicated for the treatment of adult patients with relapsed or
refractory acute myeloid leukemia (AML) with a susceptible isocitrate
dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test.SELECT
IMPORTANT SAFETY INFORMATION
WARNING:
DIFFERENTIATION SYNDROME
Differentiation
syndrome, which can be fatal, can occur with REZLIDHIA treatment. Symptoms
may include dyspnea, pulmonary infiltrates/
pleuropericardial effusion, kidney injury, hypotension,
fever, and weight gain. If differentiation syndrome is suspected, withhold
REZLIDHIA and initiate treatment with corticosteroids and hemodynamic
monitoring until symptom resolution.
|
Please
see additional Important Safety
Information
below and Full
Prescribing
Information,
including Boxed WARNING.
REZLIDHIA
CLINICAL SUMMARY*
Almost half of
patients responded
to treatment11,12
35% CR/CRh
32% CR
48% ORR
|
Over
2-year duration
of response11
25.9 months median
duration of CR/CRh
28.1 months median
duration of CR
|
Improvement
in transfusion
independence11
34% of transfusion-dependent patients
became transfusion independent
|
Well-characterized
safety profile11
8% of patients discontinued due to
adverse events
|
|
|
|
|
Olutasidenib (REZLIDHIA) is recommended by the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) as a targeted treatment option for relapsed/refractory AML with an IDH1 mutation.9
|
|
|
|
|
LEARN MORE ABOUT REZLIDHIA
Here is some additional information that you may find useful.
\
Enrollment
Form
Enroll patients in RIGEL ONECARE® for patient
support services, including benefits verification, prior authorizations, temporary
and long-term free drug supply, and adherence support. All Rigel programs are
subject to eligibility requirements. Restrictions may apply.
\Thank you for your time. I look forward to our next
appointment.\Sincerely,
|
|
|
IMPORTANT
SAFETY INFORMATION (CONT’D)
WARNINGS
AND PRECAUTIONS
Differentiation
Syndrome
REZLIDHIA can cause differentiation syndrome. In the clinical trial of
REZLIDHIA in patients with relapsed or refractory AML, differentiation syndrome
occurred in 16% of patients, with grade 3 or 4 differentiation syndrome occurring in
8% of patients treated, and fatalities in 1% of patients. Differentiation syndrome
is associated with rapid proliferation and differentiation of myeloid cells and may
be life-threatening or fatal. Symptoms of differentiation syndrome in patients
treated with REZLIDHIA included leukocytosis, dyspnea, pulmonary
infiltrates/
pleuropericardial
effusion, kidney injury, fever, edema, pyrexia, and weight gain. Of the 25 patients
who experienced differentiation syndrome, 19 (76%) recovered after treatment or
after dose interruption of REZLIDHIA. Differentiation syndrome occurred as early as
1 day and up to 18 months after REZLIDHIA initiation and has been observed with or
without concomitant leukocytosis.If differentiation syndrome is suspected, temporarily withhold REZLIDHIA and
initiate systemic corticosteroids (e.g., dexamethasone 10 mg IV every 12 hours) for
a minimum of 3 days and until resolution of signs and symptoms. If concomitant
leukocytosis is observed, initiate treatment with hydroxyurea, as clinically
indicated. Taper corticosteroids and hydroxyurea after resolution of symptoms.
Differentiation syndrome may recur with premature discontinuation of corticosteroids
and/or hydroxyurea treatment. Institute supportive measures and hemodynamic
monitoring until improvement; withhold dose of REZLIDHIA and consider dose reduction
based on recurrence.Hepatotoxicity
REZLIDHIA can cause hepatotoxicity, presenting as increased alanine
aminotransferase (ALT), increased aspartate aminotransferase (AST), increased blood
alkaline phosphatase, and/or elevated bilirubin. Of 153 patients with relapsed or
refractory AML who received REZLIDHIA, hepatotoxicity occurred in 23% of patients;
13% experienced grade 3 or 4 hepatotoxicity. One patient treated with REZLIDHIA in
combination with azacitidine in the clinical trial, a combination for which
REZLIDHIA is not indicated, died from complications of drug-induced liver injury.
The median time to onset of hepatotoxicity in patients with relapsed or refractory
AML treated with REZLIDHIA was 1.2 months (range: 1 day to 17.5 months) after
REZLIDHIA initiation, and the median time to resolution was 12 days (range: 1 day to
17 months). The most common hepatotoxicities were elevations of ALT, AST, blood
alkaline phosphatase, and blood bilirubin.Monitor patients frequently for clinical symptoms of hepatic dysfunction
such as fatigue, anorexia, right upper abdominal discomfort, dark urine, or
jaundice. Obtain baseline liver function tests prior to initiation of REZLIDHIA, at
least once weekly for the first two months, once every other week for the third
month, once in the fourth month, and once every other month for the duration of
therapy. If hepatic dysfunction occurs, withhold, reduce, or permanently discontinue
REZLIDHIA based on recurrence/severity.ADVERSE
REACTIONS
The most common (≥20%) adverse reactions, including laboratory
abnormalities, were aspartate aminotransferase increased, alanine aminotransferase
increased, potassium decreased, sodium decreased, alkaline phosphatase increased,
nausea, creatinine increased, fatigue/malaise, arthralgia, constipation, lymphocytes
increased, bilirubin increased, leukocytosis, uric acid increased, dyspnea, pyrexia,
rash, lipase increased, mucositis, diarrhea and transaminitis.DRUG
INTERACTIONS
|
• |
Avoid concomitant use of REZLIDHIA with strong or moderate CYP3A inducers.
|
|
• |
Avoid concomitant use of REZLIDHIA with sensitive CYP3A substrates unless
otherwise instructed in the substrates prescribing information. If
concomitant use is unavoidable, monitor patients for loss of therapeutic
effect of these drugs. |
LACTATION
Advise women not to breastfeed during treatment with REZLIDHIA and for 2
weeks after the last dose.GERIATRIC
USE
No overall differences in effectiveness were observed between patients 65
years and older and younger patients. Compared to patients younger than 65 years of
age, an increase in incidence of hepatotoxicity and hypertension was observed in
patients ≥65 years of age.HEPATIC
IMPAIRMENT
In patients with mild or moderate hepatic impairment, closely monitor for
increased probability of differentiation syndrome.Please
see REZLIDHIAhcp.com
for Full
Prescribing
Information, including Boxed
WARNING.
|
|
|
REFERENCES:
1.
DiNardo CD, Cortes JE. Mutations in AML: prognostic and therapeutic implications.
Hematology Am Soc Hematol Educ Program. 2016;2016(1):348-355.
doi:10.1182/asheducation-2016.1.348 2.
Tenold ME, Moskoff BN, Benjamin DJ, et al. Outcomes of adults with
relapsed/refractory acute myeloid leukemia treated with venetoclax plus
hypomethylating agents at a comprehensive cancer center. Front Oncol.
Published online March 11, 2021. doi:10.3389/fonc.2021.649209 3.
Saultz JN, Garzon R. Acute myeloid leukemia: a concise review. J Clin Med.
2016;5(33). doi:10.3390/jcm5030033 4.
Cancer stat facts: leukemia — acute myeloid leukemia (AML). National Cancer
Institute. Accessed July 20, 2023.
https://seer.cancer.gov/statfacts/html/amyl.html 5.
SEER Explorer. Acute myeloid leukemia (AML) SEER 5-year relative survival rates,
2013-2019. National Cancer Institute. Accessed July 20, 2023. Link
to data. 6.
Walter RB, Othus M, Burnett AK, et al. Resistance prediction in AML: analysis of
4,601 patients from MRC/NCRI, HOVON/SAKK, SWOG, and MD Anderson Cancer Center.
Leukemia. 2015;29(2):312-320. doi:10.1038/ leu.2014.242 7.
Abbas S, Lugthart S, Kavelaars FG, et al. Acquired mutations in the genes encoding
IDH1 and IDH2 both are recurrent aberrations in acute myeloid leukemia: prevalence
and prognostic value. Blood. 2010;116(12):2122-2126.
doi:10.1182/blood-2009-11-250878 8.
Chotirat S, Thongnoppakhun W, Promsuwicha O, Boonthimat C, Auewarakul CU. Molecular
alterations of isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) metabolic genes and
additional genetic mutations in newly diagnosed acute myeloid leukemia patients.
J Hematol Oncol. 2012;5(5). doi:10.1186/1756-8722-5-5 9.
Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology
(NCCN Guidelines®) for Acute
Myeloid Leukemia V.4.2023. © National Comprehensive Cancer Network, Inc. 2023.
All rights reserved. Accessed July 28, 2023. To view the most recent and
complete version of the guideline, go online to NCCN.org. NCCN makes no
warranties of any kind whatsoever regarding their content, use or application and
disclaims any responsibility for their application or use in any way. 10.
DiNardo CD, Ravandi F, Agresta S, et al. Characteristics, clinical outcome, and
prognostic significance of IDH mutations in AML. Am J Hematol.
2015;90(8):732-736. doi:10.1002/ajh.24072 11.
REZLIDHIA®. Package
insert. Rigel Pharmaceuticals, Inc; 2022. 12.
de Botton S, Fenaux P, Yee K, et al. Olutasidenib (FT-2102) induces durable complete
remissions in patients with relapsed or refractory IDH1-mutated AML. Blood
Adv. 2023;7(13):3117-3127. doi:10.1182/bloodadvances.2022009411
|
|
|
|
|
