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PATIENTS WITH RELAPSED/REFRACTORY
mIDH1 AML HAVE A POOR PROGNOSIS
PATIENTS WITH RELAPSED/ REFRACTORY mIDH1 AML HAVE A POOR PROGNOSIS
\Hello \ \Dr. \ \##accFname##,
\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.
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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
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Over half (57%) of patients with AML treated with induction therapy die or have relapsed/refractory AML within 12 months of diagnosis.6
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IDH1 GENE MUTATIONS HAVE BEEN REPORTED
IN 6% TO 9% OF PATIENTS
WITH AML
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In such a vulnerable patient population, it’s important to test for IDH1, an identified, actionable mutation with options for targeted treatment.7-9
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REZLIDHIA INDUCES DURABLE COMPLETE REMISSIONS
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REZLIDHIA INDUCES DURABLE COMPLETE REMISSIONS
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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.
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SELECT IMPORTANT SAFETY INFORMATION
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WARNING: DIFFERENTIATION SYNDROME
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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.
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REZLIDHIA CLINICAL SUMMARY*
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Almost half of patients achieved a composite complete remission10-12
35% CR/CRh
32% CR
45% CRc
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Over 2-year duration of response12
25.3 months median
duration of CR/CRh
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High-risk subgroups saw results consistent with overall population11-16
Post-venetoclax (n=12): 50% CRc
Post-intensive chemotherapy† (n=13):
46% CRc
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Median time to response was
less than 2 months12
88% of responders achieved
CR/CRh within 4 months
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Well-characterized safety profile10,12
Long-term use revealed no new safety signals
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View the efficacy and safety of REZLIDHIA from the pivotal trial and long-term analysis.
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For patients with mIDH1 AML who relapse or are refractory to initial treatment, choose REZLIDHIA as the first R/R targeted therapy
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Here is some additional information that you may find useful.
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Clinical Publication: Olutasidenib (FT-2102) induces durable complete remissions in patients with relapsed or refractory IDH1-mutated AML
Review the results of the REZLIDHIA clinical trial in Blood Advances for details about efficacy, safety, and more.
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Clinical Publication: Olutasidenib for Mutated IDH1 Acute Myeloid Leukemia: Final Five-Year Results From the Phase 2 Pivotal Cohort
Learn about the final 5-year efficacy and safety results from the REZLIDHIA pivotal cohort in the Journal of Hematology & Oncology.
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RIGEL ONECARE®
Find support for every step of treatment, including how to access REZLIDHIA, copay assistance, patient support services, and downloadable resources for you and your patients.
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Download the REZLIDHIA Patient Education Guide
Important information for patients about what to expect with REZLIDHIA when starting treatment.
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Download the REZLIDHIA Dosing Guide
Information on REZLIDHIA dosing and administration, monitoring, and dose modifications to manage potential adverse reactions.
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Download the Distribution Guide
Find information on REZLIDHIA distribution and pharmacy networks, and patient support services.
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Download the 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.
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\Thank you for your time. I look forward to our
next appointment.
\Sincerely,
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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
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Avoid concomitant use of REZLIDHIA with strong or moderate
CYP3A inducers.
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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.
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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.
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.3.2026. © National Comprehensive Cancer Network, Inc. 2025. All rights
reserved. Accessed January 21, 2026. 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. REZLIDHIA®. Package insert. Rigel Pharmaceuticals, Inc; 2022.
11. 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
12. Cortes J, Curti A, Fenaux P, et al. Olutasidenib for mutated IDH1 acute myeloid leukemia: final five-year results from the phase 2 pivotal cohort. J Hematol Oncol. 2025;18(1):102. doi:10.1186/s13045-025-01751-w
13. Data on file, Rigel Pharmaceuticals, Inc. January 2025.
14. Cortes J, Curti A, Fenaux P, et al. Olutasidenib for mutated
IDH1 acute myeloid leukemia: final five-year results from the phase 2 pivotal cohort
(supplemental data). J Hematol Oncol. 2025; https://link.springer.com/article/10.1186/s13045-025-01751-w#Sec20
15. Maiti A, Rausch CR, Cortes JE, et al. Outcomes of relapsed or refractory acute myeloid leukemia after frontline hypomethylating agent and venetoclax regimens. Haematologica. 2021;106(3):894-898. doi:10.3324/haematol.2020.252569
16. Niscola P, Gianfelici V, Catalano G, et al.
Acute myeloid leukemia in older patients: from new biological insights to targeted therapies. Curr Oncol. 2024;31(11):6632-6658. Error in Figure 1 legend. Correction. Curr Oncol. 2025;32(7):386. doi:10.3390/curroncol32070386
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