COURTNEY DINARDO (HOUSTON)
THE ROLE OF IDH1/2 INHIBITORS AS MONOTHERAPY
Dept. of Leukemia, The University of Texas at MD Anderson Cancer Center, Houston, USA
Mutations in IDH1 and IDH2 occur in approximately 20% of patients with AML, occurring more
frequently in patients of advanced ages. The presence of IDH mutations and the role of IDH-directed
therapy is thus particularly relevant in discussions regarding lower intensity treatment options for
older patients who are inappropriate for intensive chemotherapy.
Recently, oral targeted inhibitors of mutant IDH1 and 2 have been approved by the US Food and
Drug Administration as single agent therapies, enasidenib for patients with IDH2-mutated AML and
ivosidenib for patients with IDH1-mutated AML. Several other IDH inhibitors are in ongoing clinical
development.
As single agents, the approved targeted inhibitors enasidenib and ivosidenib are safe and effective,
leading to an approximately 20% CR and 40% ORR rate. Responses typically occur with a median of
2-3 months, and median overall survival in relapsed patients with either agent is ~9 months overall.
In patients achieving a true CR, median OS extends well beyond 12 months.
Thus while many patients do very well with IDH inhibitor therapy, not all patients respond, and most
responding patients will ultimately relapse with single-agent therapy. Importantly, the IDH1/2
inhibitors have few drug–drug interactions, suggesting non-overlapping toxicity with other effective
anti-leukemic strategies. As such, several combination strategies involving IDH inhibitors are being
evaluated in clinical trials, suggesting a future which will incorporate the IDH inhibitors in even more
effective combinations leading to improved and more durable efficacy.
SCIENTIFIC
PROGRAMME
RARE SUBSETS OF
ACUTE LEUKAEMIA
TRACKING LEUKAEMIC
STEM CELLS (LSCs)
ROUTINE DIAGNOSIS
GENE EXPRESSION
AND MUTATIONAL
PROFILING
DEBATE 1 – ALL
PATIENTS WITH
INTERMEDIATE-RISK
AML MUST BE
TRANSPLANTED
INTERACTIVE
CASES 1 – MUTATION-BASED
THERAPY
OFF-LABEL
ROUNDTABLE –
SHOULD WE REALLY
USE NEW TARGETED
INHIBITORS AS SINGLE
AGENTS ?
ADDITION OF A 3RD
AGENT TO FRONTLINE
7+3
ROUNDTABLE –
CURATIVE OPTIONS
FOR OLDER AML
INTERACTIVE CASES 2
DEBATE 2 - BEST
TREATMENT FOR
NPM1-MUTATED AML IN
THE NEXT FUTURE ?
ALLOGENEIC
HAEMATOPOIETIC
STEM CELL
TRANSPLANTATION
(HSCT)
IMMUNOTHERAPY FOR
ACUTE LEUKAEMIA
DEBATE 3 - T-ALL:
WHERE ARE WE GOING
NOW?
SELECTED ABSTRACTS
AND CLINICAL
CASES FOR AN ORAL
PRESENTATION
SELECTED ABSTRACTS
FOR A POSTER
PRESENTATION
DISCLOSURES