MEET A REAL PATIENT WITH R/R mIDH1 AML TREATED WITH REZLIDHIA
Transform expectations of clinical outcomes post venetoclax
Virtually all patients with acute myeloid leukemia (AML) eventually relapse or become intolerant or develop resistance to venetoclax-based treatment,
even after a favorable initial result.1-8
Effective treatment after a venetoclax-based regimen is an area of
urgent unmet clinical need.1,2,4-8
MEET RUTH*
An 82-year-old White female with relapsed/refractory mIDH1 AML
Ruth was initially diagnosed with myelodysplastic syndrome (MDS) with isolated del(5q). Three years later, she was diagnosed with AML. She began treatment with venetoclax + azacitidine but was only able to complete 1 cycle due to persistent myelosuppression. Ruth then initiated treatment with REZLIDHIA.
This case study contains data from an actual patient. The case studies are intended for general medical education purposes only and are not a substitute for independent clinical medical judgment. The intent of this case study is to present the experience of the individual patient, which may not represent the outcomes in the overall patient population. Response to treatment may vary from patient to patient.
Ruth was initially diagnosed with myelodysplastic syndrome (MDS) with isolated del(5q). Three years later, she was diagnosed with AML. She began treatment with venetoclax + azacitidine but was only able to complete 1 cycle due to persistent myelosuppression. Ruth then initiated treatment with REZLIDHIA.
This case study contains data from an actual patient. The case studies are intended for general medical education purposes only and are not a substitute for independent clinical medical judgment. The intent of this case study is to present the experience of the individual patient, which may not represent the outcomes in the overall patient population. Response to treatment may vary from patient to patient.
See below for her complete treatment history and response to REZLIDHIA.
Click to view important moments within Ruth’s treatment journey
Marrow evaluation deferred given clinical benefit being clearly derived with suspicion for ongoing remission based on peripheral blood studies.
ANC=absolute neutrophil count; BID=twice a day; CR=complete remission; CRh=complete remission with partial hematologic recovery; IDH1=isocitrate dehydrogenase-1; MFC-MRD=multiparametric flow cytometry for measurable residual disease; mIDH1=mutated isocitrate dehydrogenase-1; RBC=red blood cell; R/R=relapsed/refractory VRE=vancomycin-resistant Enterococci.
Real-world use of REZLIDHIA suggests durable remission is possible in a post-venetoclax setting, as seen in Ruth who9:
This case study contains data from an actual patient. The case studies are intended for general medical education purposes only and are not a substitute for independent clinical medical judgment. The intent of this case study is to present the experience of the individual patient, which may not represent the outcomes in the overall patient population. Response to treatment may vary from patient to patient.
References:
- Bewersdorf JP, Shallis RM, Derkach A, et al. Efficacy of FLT3 and IDH1/2 inhibitors in patients with acute myeloid leukemia previously treated with venetoclax. Leuk Res. 2022;122:106942. doi:10.1016/j.leukres.2022.106942
- Abaza Y, Winer ES, Murthy GSG, et al. Clinical outcomes of hypomethylating agents plus venetoclax as frontline treatment in patients 75 years and older with acute myeloid leukemia: real-world data from eight US academic centers. Am J Hematol. 2024;99(4):606-614. doi:10.1002/ajh.27231
- Gangat N, Ilyas R, Johnson IM, et al. Outcome of patients with acute myeloid leukemia following failure of frontline venetoclax plus hypomethylating agent therapy. Haematologica. 2023;108(11):3170-3174. doi:10.3324/haematol.2022.282677
- Khanna V, Azenkot T, Liu SQ, et al. Outcomes with molecularly targeted agents as salvage therapy following frontline venetoclax + hypomethylating agent in adults with acute myeloid leukemia: a multicenter retrospective analysis. Leuk Res. 2023;131:107331. doi:10.1016/j.leukres.2023.107331
- Maiti A, Qiao W, Sasaki K, et al. Venetoclax with decitabine vs intensive chemotherapy in acute myeloid leukemia: a propensity score matched analysis stratified by risk of treatment-related mortality. Am J Hematol. 2021;96(3):282-291. doi:10.1002/ajh.26061
- 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. 2021;11:649209. doi:10.3389/fonc.2021.649209
- Thol F, Döhner H, Ganser A. How I treat refractory and relapsed acute myeloid leukemia. Blood. 2024;143(1):11-20. doi:10.1182/blood.2023022481
- Cortes J, Jonas BA, Schiller G, et al. Olutasidenib in post-venetoclax patients with mutant isocitrate dehydrogenase 1 (mIDH1) acute myeloid leukemia (AML). Leuk Lymphoma. 2024;65(8):1145-1152. doi:10.1080/10428194.2024.2333451
- REZLIDHIA®. Package insert. Rigel Pharmaceuticals, Inc; 2022.
INDICATION AND IMPORTANT SAFETY INFORMATION, INCLUDING BOXED WARNING
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.
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.
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 Full Prescribing Information, including Boxed WARNING.
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.
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.
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 Full Prescribing Information, including Boxed WARNING.