Olutasidenib demonstrates significant clinical activity in mutated IDH1 acute myeloid leukaemia arising from a prior myeloproliferative neoplasm

Summary

Acute myeloid leukaemia (AML) arising from a myeloproliferative neoplasm (MPN) is more aggressive and less responsive to therapies compared to de novo AML. Olutasidenib, an oral small‐molecule inhibitor of mutated IDH1 (mIDH1), showed encouraging and durable responses in a phase 1/2 study of adults with post‐MPN mIDH1 AML. Patients received olutasidenib 150 mg BID monotherapy or in combination with azacitidine. Primary end‐points: safety and best response defined as complete remission (CR), CR with partial haematological recovery or morphological leukaemia‐free state (MLFS). Analysis included 15 patients with post‐MPN mIDH1 AML; 10 had relapsed or refractory AML and five had newly diagnosed AML. Six were treated with olutasidenib monotherapy and nine in combination with azacitidine. Treatment emergent adverse events occurred in 15 patients, three of whom discontinued therapy. CR: 40% (n = 6/15); median duration of response: 15.6 months (range: 1.7–44.3); CR with incomplete haematological recovery: 13% (n = 2/15); MLFS: 7% (n = 1/15); composite complete remission (CRc): 53% (n = 8/15); and overall response rate (ORR): 60% (9/18). Median duration of CRc and ORR: 13.15 (range: 2.4–48.7) and 14.3 months (range: 2.4–48.7), respectively, and median overall survival: 13.8 months (95% confidence interval: 3.70–23.7). Olutasidenib demonstrated encouraging response rates with a manageable safety profile for patients with post‐MPN mIDH1 AML.

Outcomes with olutasidenib appear appreciably better than previous reports of other therapies for blast‐phase myeloproliferative neoplasm (MPN), supporting the role for olutasidenib‐based therapy in mIDH1 AML secondary to MPN.

INTRODUCTION

Acute myeloid leukaemia (AML) evolving from myeloproliferative neoplasms (MPNs) represents a subtype of secondary AML associated with poor response to available therapies and an overall dismal survival outcome. ¹ To date, there are no standard treatment options and there has been little therapeutic advancement over time. ¹ Allogeneic stem cell transplant (allo‐SCT) offers the best opportunity for long‐term survival; however, as with de novo AML, allo‐SCT is usually pursued after achieving disease control. This point is likely even more important in patients with an underlying MPN, where suboptimal disease control can lead to graft failure.

Somatic mutations in the isocitrate dehydrogenase 1/2 (IDH1/2) genes can occur in approximately 20% of myeloid malignancies. ² , ³ , ⁴ , ⁵ Under normal circumstances, wild‐type IDH1/2 enzymes catalyse isocitrate to alpha‐ketoglutarate (αKG); however, when mutated, IDH1/2 reduces αKG to the oncometabolite 2‐hydroxyglutarate (2‐HG). ⁵ 2‐HG interferes with normal cellular metabolism and epigenetic regulation contributing to oncogenesis. ⁵ , ⁶ In MPNs, IDH1/2 mutations are encountered in 1%–4% of patients with chronic‐phase MPN, but increases to 21% in blast‐phase MPN (MPN‐BP or post‐MPN AML), highlighting their significant role in MPN transformation. ⁷ , ⁸ , ⁹ , ¹⁰ In murine models, co‐occurring JAK2 ^V617F , the most common driver mutation in MPNs and an IDH1 ^R132H or IDH2 ^R140Q mutation induced a more aggressive MPN phenotype characterized by expansion of pathological stem and progenitor cell populations and impaired haematopoietic differentiation, in comparison with control mice expressing an IDH1, IDH2 or JAK2 mutation alone. ⁷ , ¹¹ In the clinical setting, the presence of an IDH1/2 mutation confers a higher rate of AML incidence and inferior overall survival (OS) and leukaemia‐free survival in patients with JAK2 ^V617K MPN. ¹⁰ Thus, both nonclinical and clinical data suggest a facilitatory role of mutated IDH1/2 in MPN disease progression and support a therapeutic role of inhibiting mutated IDH1/2 blasts in post‐MPN AML.

Olutasidenib is an oral, selective and potent inhibitor of the mutated IDH1 (mIDH1) protein that is approved by the United States Food and Drug Administration (FDA) for relapsed/refractory (R/R) AML harbouring an IDH1 mutation (mIDH1) based on the results from the pivotal cohort of a registrational phase 1/2 multi‐centre, open‐label, multi‐cohort trial (NCT02719574). The study evaluated olutasidenib monotherapy or in combination with azacitidine in patients with newly diagnosed or R/R mIDH1 AML or myelodysplastic syndrome. The phase 2 pivotal R/R AML cohort demonstrated a complete response (CR) or CR with partial haematological recovery (CRh) rate of 35%, with a 25.9‐month median duration of CR/CRh, leading to the FDA approval of olutasidenib. ¹² Here, we report the clinical and disease characteristics and outcomes of patients with secondary AML arising from prior MPN who enrolled on the trial.

METHODS

As previously reported, this was a multicentre, multinational, open‐label, multicohort phase 1/2 trial (NCT02719574) designed to investigate the efficacy and safety of olutasidenib as monotherapy or in combination with azacitidine in patients with AML or myelodysplastic syndromes harbouring IDH1 ^R132 mutations. ¹² , ¹³ Patients included in this subset analysis were males and females aged 18 years and older with pathologically confirmed secondary AML arising from prior MPN and harbouring mIDH1 ^R132 mutations. These patients were either treatment‐naïve or R/R to standard treatment. Pretreatment samples of peripheral blood or bone marrow aspirate were used for central confirmation of mutation status. Key inclusion criteria required an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2, adequate liver and renal function, negative pregnancy test for women and baseline‐corrected QT interval by Fridericia (QTcF) of ≤450 ms. Patients with a history of previous malignancy, prior IDH inhibitor therapy use, uncontrolled infections or metabolic disorders or significant heart disease were excluded.

Primary study end‐points included evaluation of safety (dose‐limiting toxicities and adverse events [AEs]) and the best response determined by applicable disease criteria derived from the International Working Group criteria for AML and myelodysplastic syndrome. The best response was CR, CRh, CR with incomplete haematological recovery (CRi) or morphologic leukaemia‐free state (MLFS). CRh was defined as bone marrow blasts <5% with an absolute neutrophil count >0.5 × 10⁹/L and a platelet count that was >50 × 10⁹/L. AEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA) coding system (version 21.0) using system organ class (SOC) and the preferred term (PT) and graded using the National Cancer Institute‐Common Terminology for Adverse Events (NCI‐CTCAE) version 4.03.

Olutasidenib was provided at a dose of 150 mg twice daily as a single agent or in combination with intravenous or subcutaneous azacitidine at 75 mg/m²/dose × 7 days/cycle every 28 days.

For this subset analysis, descriptive statistics were used to characterize treatment response. Median duration of response (mDoR) and OS were calculated using the Kaplan–Meier method. Survival curves for responders versus non‐responders were generated using the Mantel–Byar method to address potential immortal time bias. No formal statistical testing was performed and a formal power calculation was not required.

The study was conducted in accordance with the Good Clinical Practice guidelines and the Declaration of Helsinki. The Institutional Review Board or Ethics Committee at each study site provided protocol approval and all patients provided written informed consent.

RESULTS

Patients

Among the 336 patients who enrolled in the phase 1/2 study, 15 patients with a prior history of MPN that transformed to AML were identified and included in this analysis. Median age at diagnosis was 67 years (range: 48–83). Male to female ratio was 10:5. Of the 15 patients, five patients had newly diagnosed AML and 10 had R/R AML, including six from the pivotal cohort, with a median of two prior therapies (range: 1–6). Primary MPN diagnoses were polycythaemia vera in three, essential thrombocythaemia in three, primary myelofibrosis in six and MPN not otherwise specified in three patients; four patients had splenomegaly in their prior medical history. Median baseline bone marrow blast percentage was 35% (range: 8%–90%). IDH1 mutation type was R132C in 10, R132H in four and R132G in one patient. Three patients did not have a mutational profile completed at enrolment, but in the remaining 12, co‐mutations included JAK2 (n = 9); ASXL1 (n = 6); SRSF2 (n = 5); RUNX1 (n = 4); MPL, CALR and FLT3 (n = 2 each); and STAG2, TP53, WT1, IDH2, NRAS, CBL, U2AF1, E2H1, SETP1 and DNMT3 (n = 1 each). Cytogenetic risk status was intermediate in 11, poor in three and unknown in one patient. Cytogenetic findings included seven patients with a normal karyotype, three with complex karyotype, one with monosomy 7 and four with unknown or other karyotypes. Table 1 details patient and disease characteristics. Six patients were treated with olutasidenib monotherapy at the labelled dose of 150 mg BID and nine received olutasidenib 150 mg BID in combination with azacitidine.

TABLE 1.

Patient and disease characteristics. [Colour table can be viewed at wileyonlinelibrary.com]

Best response	Responders									Non‐responders				Un‐evaluable
	CR	CR	CR	CR	CR	CR	CRi	CRi	MLFS	CB	SD	SD	PD
Age (years)	66	75	67	67	67	70	54	71	48	66	63	77	83	70	72
Gender	F	F	M	F	M	M	M	M	M	F	M	M	M	M	F
Primary MPN diagnosis	PV	PV	PV	NOS	MF	MF	MF	ET	NOS	MF	MF	ET	NOS	MF	ET
AML disease status	RR	RR	ND	RR	RR	ND	RR	ND	RR	ND	RR	RR	RR	ND	RR
Bone marrow blast (%)	28	40	60	57	15	35	90	34	8	86	30	82	23	60	23
Study treatment	Olu	Olu Aza	Olu Aza	Olu Aza	Olu	Olu Aza	Olu	Olu Aza	Olu Aza	Olu Aza	Olu Aza	Olu	Olu	Olu Aza	Olu
IDH1 R132 mutation	C	C	C	C	H	H	C	H	C	C	H	G	C	C	C
Cytogenetic risk classification	Int	Int	Int	Po	Int	Int	Int	Int	Int	Unk	Po	Po	Int	Int	Int
Cytogenetic	Nl	Co	Oth	Co	Nl	Nl	Oth	Nl	Nl	Unk	Co	Mo	Nl	Oth	Nl
Mutational profile*	NA					NA									NA
JAK2
ASXL1
SRSF2
RUNX1
MPL
STAG2
CALR
TP53
FLT3
NPM1
NRAS
CBL
EZH2
SETP1
DNMT3
IDH2
U2AF1
WT1

Abbreviations: Aza, azacitidine; CB, clinical benefit; Co, complex; CR, complete response; CRi, complete response with haematological recovery; ET, essential thrombocythaemia; Int, intermediate; MF, myelofibrosis; MLFS, morphologic leukaemia free status; Mo, monosomy 7; MPN, myeloproliferative neoplasm; NA, not available; ND, newly diagnosed; Nl, normal; NOS, not otherwise specified; Olu, olutasidenib; Oth, other; PD, progressive disease; Po, poor; PV, polycythaemia vera; RR, relapsed refractory; SD, stable disease; Unk, unknown.

*Blue shading indicates mutation present.

Efficacy

Of the 15 patients, 6 (40%) had a CR and 2 (13%) had a CRi, giving a composite complete response (CRc; CR + CRi) in 8 (53%). The median times to response for CR and CRc were 3.8 months (range: 2–7) and 1.9 months (range: 1–6) respectively. The median duration of CR was 15.6 months (range: 1.7–44.3) and of CRc was 13.15 months (range: 2.4–48.7). One patient had MLFS leading to an overall response rate (ORR; CR + CRi + MLFS) in 9/15 (60%), with a median duration of ORR of 14.3 months (range: 2.4–48.7). Two patients discontinued study treatment within 28 days of the start of therapy due to an AE or patient decision and did not have disease response assessment. The CR, CRc and ORR rates among disease‐evaluable patients were 46% (6/13), 62% (8/13) and 69% (9/13) respectively. Of the eight patients who achieved a CRc, three were treated with olutasidenib monotherapy and five were treated with olutasidenib and azacitidine. Two patients who responded with a CR subsequently received an allo‐SCT. With a median follow‐up of 55.3 months, the median overall survival (mOS) was: 13.8 months (95% confidence interval [CI]: 3.70–23.7; range: 1.6–55.3) in all 15 patients, 24.8 months (95% CI: 13.8, not reached; range: 13.8–55.3) in patients with CR (Figure 1A). In responders, mOS was 20.9 months (95% CI: 4.4–44.3) and in non‐responders was 4.1 months (95% CI: 1.6, not reached; Figure 1B).

FIGURE 1.

Overall survival: (A) Kaplan–Meier estimates for all patients and (B) survival in responders (CR + CRi + MLFS) and non‐responders (CB + SD + PD) using the Mantel–Byar method. CB, clinical benefit; CR, complete response; CRi, complete response with haematological recovery; MLFS, morphologic leukaemia free status; PD, progressive disease; SD, stable disease.

Safety

All 15 (100%) patients experienced a treatment‐emergent adverse event (TEAE) of any grade and 11 (73%) had grade 3–4 TEAEs. The most frequent (≥20%) grade 3–4 TEAEs were red blood count decreased, occurring in 6 (40%) patients, infections in 5 (33%), neutrophil count decreased in 4 (27%) and febrile neutropenia in 4 (27%). Three patients discontinued therapy due to TEAEs: grade 4 increased GGT, nasal mucosal melanoma and hepatotoxicity (characterized by asymptomatic grade 2–4 liver function test elevations leading to hospitalization). Of the three patients, one patient was on monotherapy, and two were on combination therapy.

DISCUSSION

The patient and disease characteristics of our cohort are consistent with what has been reported for post‐MPN AML patients; namely, an older patient population, male predominance, MF as the most common antecedent MPN, presence of the canonical JAK2 mutation in the majority of cases followed by MPL and CALR in a smaller number and common co‐mutations including ASXL1, SRSF2 and RUNX1 that confer a higher risk for leukaemic transformation. ⁹ , ¹⁴ , ¹⁵

At present, treatment options for post‐MPN AML include intensive induction chemotherapy, allo‐SCT, hypomethylating agent (HMA) with or without venetoclax or HMA with or without a JAK2 inhibitor. ¹⁶ Unfortunately, these treatments do not significantly prolong survival apart from allo‐SCT. ¹ Tefferi et al. completed an analysis of 248 patients with MPN‐BP and observed a 35% CR and 24% CRi rate and mOS of 4.9 months following intensive induction chemotherapy. ¹⁴ In a large review of allo‐SCT outcomes for MPN‐BP that assessed 663 patients, the estimated 3‐year OS was 36%. ¹⁷

Published data for MPN patients who received HMA report CR rates ranging from 4% to 26% and mOS from 9.9 to 11 months. ¹⁴ , ¹⁸ , ¹⁹ In a phase 3 registrational trial of older patients with newly diagnosed secondary AML, liposomal cytarabine and daunorubicin (CPX‐351) significantly improved OS compared to standard induction chemotherapy with cytarabine/anthracycline (commonly referred to as ‘7 + 3’); however, patients with post‐MPN AML were excluded from this trial. ²⁰ To address this gap in the exclusion of post‐MPN AML patients, a recent retrospective study evaluated 12 patients with MPN‐BP treated with CPX‐351, reporting a CR rate of 35%, ²¹ similar to the response rates observed when MPN‐BP is treated with HMA and venetoclax. ²² Interestingly, some patients who initially failed treatment with CPX‐351 subsequently achieved CR after receiving salvage therapy with HMA and venetoclax, and then proceeded to allo‐SCT. ²¹

The advent of venetoclax has significantly changed the treatment landscape for AML. A recent study in treatment‐naïve patients with mIDH1 AML treated with HMA and venetoclax reported response rates (CRc: 66.7%) and mOS (15.2 months) and durable remissions (mDoR: 21.9 months). ²³ However, the role of venetoclax combination therapy in the treatment of MPN is still unknown. In retrospective reports of venetoclax and HMA in post‐MPN AML, the CR rates ranged from 11% to 26% and CRi occurred in 10%–24% of patients, and the mOS was 4–7 months, suggesting a limited benefit of venetoclax in this population. ¹⁵ Venetoclax‐based regimens had a high incidence (i.e. 80%) of grade 3 or higher AEs related to bone marrow suppression (e.g. infections and haemorrhage) due to the underlying AML, effects of venetoclax on normal haematopoiesis and the attendant bone marrow fibrosis and/or osteosclerosis present in many MPN patients. ¹⁵ , ²³ , ²⁴ , ²⁵ In contrast, in this subset analysis, patients treated with olutasidenib experienced fewer AEs associated with bone marrow suppression, suggesting that combination therapy with olutasidenib, HMA and venetoclax may not significantly increase toxicity compared to conventional regimens. Notably, in a phase 1b study, combination therapy with the IDH inhibitor ivosidenib, along with venetoclax and azacitidine, resulted in an ORR of 100% and a CRc rate of 90% compared to 83% without azacitidine, with a safety profile comparable to that of ivosidenib/azacitidine or azacitidine/venetoclax. ²⁶ Therefore, further research into olutasidenib combination regimens is warranted. Given the potential for enhanced efficacy and a tolerable safety profile compared to conventional regimens, investigations are underway to assess olutasidenib in combination with other agents for AML and other haematological cancers. ²⁷

The combination of ruxolitinib, a JAK2 inhibitor and HMA has also been employed in advanced MPN with the primary aim of reducing splenomegaly and disease‐related symptoms. ²⁸ , ²⁹ Here, in different studies all utilizing ruxolitinib, the observed CR rates fell between 0% and 27% and the CRi rates between 8% and 34%, with an mOS of 6.2–9.5 months. ¹⁵ A comparison of clinical outcomes with these best available therapies and our reported data suggest improved outcomes with olutasidenib. Specifically, in this report, 40% of patients treated with olutasidenib achieved a CR and 53% a CRc, lasting for a median of 15.6 months and 13.15 months, respectively.

The clinical activity of IDH1/2 inhibitors in mIDH1/2 post‐MPN AML has been reported in prior publications. Chifotides et al. described 12 patients with mIDH1/2 post‐MPN AML treated with IDH1/2 inhibitors (i.e. ivosidenib, olutasidenib, IDH‐305 [investigational IDH1 inhibitor] or enasidenib) and observed a CR rate of 25% with an mOS of 10 months for all patients. ⁷ Patel et al. showed that, in eight patients with mIDH2 MPN in accelerated or blast‐phase (MPN‐AP/BP) treated with enasidenib monotherapy or enasidenib and azacitidine, 25% achieved a CR with a median follow‐up of 272 days and an mOS not reached. ³⁰ Taken together, these data suggest a benefit of using IDH1/2 inhibitors in IDH1/2‐mutated advanced‐phase MPN.

To our knowledge, this report represents the largest cohort of mIDH1 AML secondary to MPN treated with an mIDH1 inhibitor. The results are encouraging with 60% (9/15) of patients attaining some level of response to olutasidenib‐based therapy and an overall mOS of 13.8 months. Both newly diagnosed (3/5, 60%) and relapsed/refractory (6/11, 55%) patients, in near equal proportions, responded to olutasidenib monotherapy or olutasidenib plus azacitidine. There appears to be a trend towards better response with olutasidenib and azacitidine with an ORR of 67% (6/9 patients) in patients receiving combination therapy, compared to an ORR of 50% (3/6 patients) in those treated with olutasidenib monotherapy, but the sample size is too small to draw a definitive conclusion.

Among the patients who responded six had a JAK2 mutation including one patient with concurrent JAK2, MPL and CALR mutations, while among the four patients who were non‐responders, two had JAK2 mutations, one had an MPL and one had a CALR mutation, suggesting a collaborative interaction of aberrant JAK2 and IDH1 in MPN disease progression and the role of an mIDH1 inhibitor in post‐MPN AML. Not unexpectedly, co‐occurring mutations in ASXL1, SRSF2 and/or RUNX1 were common and portended a more aggressive disease phenotype and lower percentage of response (e.g. CR/CRi in 2/7 [29%]). Two patients proceeded to allo‐SCT after achieving a CR with olutasidenib monotherapy, indicating that olutasidenib‐based treatments can serve as a successful bridge to allo‐SCT. Indeed, the notable limited myelosuppression with olutasidenib‐based therapy may provide an optimal platform for allo‐SCT and result in more full CR responses. Interestingly, one patient who underwent allo‐SCT received olutasidenib monotherapy as ‘maintenance’ therapy for minimal residual disease (MRD) positivity (i.e. mIDH1 MRD ≥0.01%) post‐transplant for 19 months. The second patient who received an allo‐SCT had a 12‐month duration of CR.

While the results of this subset analysis are encouraging, definitive conclusions cannot be drawn due to the inherent limitations of such subset analyses. Without adequate context from the larger study, the implications of these findings may not be fully appreciated. Nonetheless, these results can help guide future study designs and treatment strategies for patients with post‐MPN mIDH1 AML who need safe and effective therapeutic options.

CONCLUSION

The results of this subset analysis are encouraging for olutasidenib in post‐MPN mIDH1 AML and suggest it may be a potential treatment option for these patients. These results appear appreciably better than previous outcomes reported in the literature, supporting the role for olutasidenib‐based therapy in mIDH1 AML secondary to MPN. Further research is needed on the use of olutasidenib in patients with mIDH1 MPN prior to AML transformation, as early intervention with targeted therapy may be critically important for improving outcomes in these high‐risk patients.

AUTHOR CONRIBUTIONS

SDB, JC, MMC, HT and JMW made substantial contributions to conception or design of the study or analysis. All authors contributed to the acquisition, analysis or interpretation of data. SDB, JC, MMC, HT and JMW made substantial contributions to drafting the manuscript and all authors revised the drafts critically for important intellectual content. All authors reviewed and approved the final manuscript.

FUNDING INFORMATION

Funding for this study was provided by Forma Therapeutics and Rigel Pharmaceuticals. Medical writing assistance was funded by Rigel Pharmaceuticals.

CONFLICT OF INTEREST STATEMENT

SDB: Celgene, Agios, Forma, Astellas, Syros, AbbV, Bayer, Seagen, Janssen, Daiichi, Pierre Fabre, Novartis, Pfizer, SERVIER. CR: AbbV, BMS, Jazz, Amgen, Astellas, Novartis, Pfizer, Takeda, Servier. JC: AbbV, BMS, Novartis, Pfizer, BioLine, Bio‐Path, Takeda, Daiichi, Jazz, Forma, Gilead, Rigel, Sun, Terns, Genentech, Actuate, Sellas, Bio‐Path, Astellas, Amphivena. AC: Jazz, Pfizer, Novartis, AbbV. PF: AbbV, Janssen, Jazz, Novartis, BMS. PP: Jazz, Astellas, Celgene, AbbVie. AP: AbbVie, Gilead, Astellas, Agios, Pfizer, Jazz. KY: Bristol Myers Squibb/Celgene, F. Hoffmann‐La Roche, GSK, Jazz Pharmaceuticals, Novartis, Pfizer, Shattuck Labs, Taiho Oncology, Takeda, Astex Pharmaceuticals, Forma Therapeutics, Forma Therapeutics, Genentech, Geron Corporation, Gilead Sciences, Janssen Pharmaceuticals, Treadwell Therapeutics, AbbVie, TaiHo. AW: Astellas, AbbVie/Genentech, Amgen, Celgene/BMS, Novartis, Servier, Syndax, Janssen, Gilead, MacroGenetics, Pfizer, AstraZeneca and Astex. AM: BMS, AbbVie, Rigel Pharmaceuticals, Ryvu Therapeutics, Foghorn Therapeutics, Jazz Pharmaceuticals and Daiichi Sankyo. GS: Agios, Gamida, Gilead, Incyte, Amgen, BMS, Novartis, Ono Pharma, AVM Biotech, GlaxoSmithKline, Janssen/Johnson & Johnson, AbbVie, Astellas, Celgene, Karyopharm, Stemline, AstraZeneca, Actinium, Actuate, Ambit, Cellectis, Cyclacel, Constellation, Daiichi‐Sankyo, Deciphera, DeltaFly, Forma Therapeutics, FujiFilm, Genentech/Roche, Geron, Glycomimetics, Kura Oncology, Mateon, Medimmune, Millennium; Onconova, Pfizer, PrECOG, RegImmune, Sangamo, Samus, Sellas, Tolero and Trovagene. MMC, HT: Rigel. JMW: Takeda, Immune System Key Ltd., Genentech, Rafael, Reven, Celgene/BMS, Servier, Rigel, Aptose, Astellas and Daiichi.

ETHICS APPROVAL STATEMENT

The study was conducted in accordance with the Good Clinical Practice guidelines and the Declaration of Helsinki. The Institutional Review Board or Ethics Committee at each study site provided protocol approval.

PATIENT CONSENT STATEMENT

All patients provided written informed consent.

CLINICAL TRIAL REGISTRATION

Clinicaltrials.gov identifier: NCT02719574.

De Botton S, Récher C, Cortes J, Curti A, Fenaux P, Peterlin P, et al. Olutasidenib demonstrates significant clinical activity in mutated IDH1 acute myeloid leukaemia arising from a prior myeloproliferative neoplasm. Br J Haematol. 2025;206(4):1121–1128. 10.1111/bjh.19944

DATA AVAILABILITY STATEMENT

For deidentified data, requests may be sent to datasharing@rigel.com at least 24 months after clinical trial completion, provided a scientifically valid research proposal is made by qualified, academic researchers for data associated with interventions that have received regulatory approval in the United States and Europe.