These findings justify the integration of menin inhibitors into the AML therapeutic landscape, and support ongoing randomized trials to confirm their benefit in both frontline and relapse or refractory settings.

4 months ago

Journal

NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • MEIS1 (Meis Homeobox 1) • MEN1 (Menin 1)

NPM1 mutation • KMT2A rearrangement • KMT2A mutation • MLL mutation

Venclexta (venetoclax) • Revuforj (revumenib) • Komzifti (ziftomenib) • bleximenib (JNJ-6617) • enzomenib (DSP-5336)

4ms

Therapeutic Implications of Menin Inhibitors in the Treatment of Acute Leukemia: A Critical Review. (PubMed, Diseases)

Currently, six menin inhibitors are in clinical evaluation as monotherapy or in combination regimens: revumenib, ziftomenib, bleximenib (previously JNJ-75276617), enzomenib (previously DSP-5336), DS-1594, and BMF-219. We discuss their efficacy, safety profiles, and potential roles within the current treatment algorithm. The continued clinical evaluation of menin inhibitors may redefine treatment paradigms for NPM1m and KMT2Ar AML and other acute leukemia with the aberrant MEIS1-HOXA axis, offering new hope for patients with limited therapeutic options.

4 months ago

Review • Journal

NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • MEIS1 (Meis Homeobox 1)

NPM1 mutation • KMT2A rearrangement • MLL mutation

Revuforj (revumenib) • Komzifti (ziftomenib) • icovamenib (BMF-219) • bleximenib (JNJ-6617) • emilumenib succinate (DS-1594) • enzomenib (DSP-5336)

5ms

CR108998: A Phase 1/2 Study of Bleximenib in Participants With Acute Leukemia (clinicaltrials.gov)

P1/2, N=400, Recruiting, Janssen Research & Development, LLC | Trial completion date: Oct 2027 --> May 2028

5 months ago

Trial completion date

NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)

bleximenib (JNJ-6617)

6ms

Menin inhibitors from monotherapies to combination therapies: clinical trial updates from 2024 ASH annual meeting. (PubMed, J Hematol Oncol)

Following the promising outcomes of the two pioneering menin inhibitors, revumenib and ziftomenib, other menin inhibitors, including bleximenib, enzomenib, BN-104 and HMPL-506 are currently under investigation in clinical trials. Several trials presented their initial outcomes at the 2024 ASH Annual Meeting. This review highlights the key outcomes of these pivotal clinical trials.

6 months ago

Review • Journal

NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • MEIS1 (Meis Homeobox 1)

NPM1 mutation • KMT2A rearrangement

Revuforj (revumenib) • Komzifti (ziftomenib) • bleximenib (JNJ-6617) • enzomenib (DSP-5336)

6ms

cAMeLot-2: A Study of Bleximenib, Venetoclax and Azacitidine For Treatment of Participants With Acute Myeloid Leukemia (AML) (clinicaltrials.gov)

P3, N=600, Recruiting, Janssen Research & Development, LLC | Not yet recruiting --> Recruiting

6 months ago

Enrollment open

Venclexta (venetoclax) • azacitidine • bleximenib (JNJ-6617)

6ms

Menin Inhibitors in KMT2A-Rearranged and NPM1-Mutated Acute Leukemia: A Scoping Review of Safety and Efficacy. (PubMed, Crit Rev Oncol Hematol)

Menin inhibitors demonstrate promising clinical activity in molecularly defined leukemias, with Revumenib establishing proof-of-concept for this therapeutic approach. However, challenges remain, including resistance development, optimal timing of therapy initiation, and determination of effective combination strategies. Larger randomized trials with extended follow-up are needed to establish long-term efficacy and safety profiles. The rapid clinical development of multiple agents in this class suggests an expanding role for Menin inhibitors in leukemia treatment paradigms.

6 months ago

Review • Journal

NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • MEN1 (Menin 1)

NPM1 mutation • KMT2A rearrangement

Revuforj (revumenib) • Komzifti (ziftomenib) • icovamenib (BMF-219) • bleximenib (JNJ-6617) • emilumenib succinate (DS-1594) • enzomenib (DSP-5336)

7ms

CR109124: A Study of Bleximenib in Combination With Acute Myeloid Leukemia (AML) Directed Therapies (clinicaltrials.gov)

P1, N=200, Recruiting, Janssen Research & Development, LLC | Trial primary completion date: Aug 2026 --> Oct 2024

7 months ago

Trial primary completion date

NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)

Venclexta (venetoclax) • cytarabine • azacitidine • daunorubicin • idarubicin hydrochloride • bleximenib (JNJ-6617)

7ms

MENIN inhibitor-based therapy in acute leukemia: latest updates from the 2024 ASH annual meeting. (PubMed, Exp Hematol Oncol)

At the 2024 ASH annual meeting, updated clinical data regarding monotherapy with MENINis in AL, including revumenib, bleximenib, enzomenib and BN104, were presented. Furthermore, the therapeutic effects of venetoclax plus azacitidine or "3 + 7" regimens were further enhanced by the addition of MENINis in KMT2Ar- and NPM1m-AML patients. Therefore, MENINis offer new therapeutic prospects for AML patients, particularly for those with high-risky and poor-prognostic on-target subtypes.

7 months ago

Journal

NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • HOXA9 (Homeobox A9) • MEIS1 (Meis Homeobox 1)

NPM1 mutation

Venclexta (venetoclax) • azacitidine • Revuforj (revumenib) • bleximenib (JNJ-6617) • enzomenib (DSP-5336)

8ms

CR109124: A Study of Bleximenib in Combination With Acute Myeloid Leukemia (AML) Directed Therapies (clinicaltrials.gov)

P1, N=200, Recruiting, Janssen Research & Development, LLC | Trial primary completion date: Mar 2025 --> Aug 2026

8 months ago

Trial primary completion date

NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)

Venclexta (venetoclax) • cytarabine • azacitidine • daunorubicin • idarubicin hydrochloride • bleximenib (JNJ-6617)