Revuforj confirmed continued effectiveness in treating sufferers with relapsed or refractory KMT2A acute leukemia, with excessive charges of minimal residual illness negativity and development to stem cell transplant.
Sufferers with relapsed or refractory KMT2Ar acute leukemia continued to expertise clinically significant responses, akin to increased charges of minimal residual illness (MRD) negativity and the proportion of procession to hematopoietic stem cell transplant (HSCT) when handled with Revuforj (revumenib).
Up to date evaluation from the section 2 AUGMENT-101 trial introduced on the 2024 ASH Annual Assembly additionally confirmed that the protection profile of the agent continued to be manageable, with no sufferers discontinuing remedy on account of differentiation syndrome or QTc prolongation.
“This trial represents the most important analysis of a focused remedy for sufferers with relapsed/refractory KMT2Ar acute leukemias to this point, together with the most important pediatric menin inhibitor cohort,” Dr. Ibrahim Aldoss, affiliate professor, Division of Hematology & Hematopoietic Cell Transplantation, Metropolis of Hope Nationwide Medical Heart, Duarte, California, mentioned throughout a presentation of the longer follow-up. “…[Revuforj] is the primary authorised menin inhibitor and first authorised remedy for KMT2Ar acute leukemia.”
Glossary:
Minimal residual illness (MRD) negativity: the absence of small quantities of most cancers cells.
Hematopoietic stem cell transplant (HSCT): when wholesome stem cells are infused right into a affected person.
Differentiation syndrome: a critical facet impact brought on by the massive, speedy launch of cytokines from leukemia cells affected by anticancer medication, in response to the Nationwide Most cancers Institute.
QTc prolongation: when it takes longer than traditional for the guts to recharge between beats, in response to the Mayo Clinic.
Total response fee (ORR): sufferers who responded partially or fully to remedy.
Full remission (CR): the disappearance of indicators and signs of most cancers.
Full remission with partial hematologic restoration (CRh): when all indicators of most cancers have disappeared, however a affected person’s blood cell counts haven’t returned to regular ranges, in response to The College of Texas MD Anderson Most cancers Heart.
Length of response (DOR): how lengthy a affected person responds to remedy.
Febrile neutropenia: when a affected person has a fever and a low depend of white blood cells.
Anemia: a low depend of wholesome crimson blood cells.
Neutrophil: a kind of white blood cell.
Response to Revuforj
As of the information cutoff of Feb. 29, 2024, the general response fee (ORR) was 63.9%, together with a whole remission (CR) or a CR with partial hematologic restoration (CRh) fee of twenty-two.7% and composite CR (CRc) of 42.3%.
Of 18 CR+CRh responders and 36 CRc responders who had been evaluable, 11 (61.1%) and 21 (58.3%), respectively, skilled MRD negativity.
Additional, median length of response (DOR) for the 22 CR+CRh responders was 6.4 months. In complete, eight sufferers stay in follow-up with out relapse or dying. Aldoss famous that the up to date median DOR of CR+CRh for the 13 sufferers who responded to Revuforj remedy within the interim evaluation was 13 months.
The median time to first response in all responders was one month, and was two months in CR+CRh responders.
Total, 21 sufferers (33.9%) within the ORR cohort went on to obtain HSCT, of which 9 (42.9%) of them restarted remedy with Revuforj after a median of 70 days. Of the sufferers who went on to obtain HSCT, 9 of the 11 CRc responders and 4 of the six CR or CRh responders with MRD standing out there had been adverse.
No New Security Indicators
Grade 3 (extreme) or increased treatment-emergent or treatment-related unwanted effects occurred in 91.4% and 54.3% of sufferers, respectively, of which 77.6% and 36.2% had been critical. Remedy-emergent unwanted effects led to dose discount in 9.5% of sufferers and discontinuation in 13.8% of sufferers, whereas treatment-related unwanted effects led to discount and discontinuation in 8.6% and 5.2%, respectively.
The most typical grade 3 or increased treatment-emergent unwanted effects had been febrile neutropenia (38.8%), anemia (19.8%), decreased platelet depend (16.4%), differentiation syndrome (14.7%), decreased neutrophil depend (14.7%), decreased white blood cell depend (14.7%), sepsis (13.8%) and QTc prolongation (12.9%). No new security indicators had been reported and no sufferers discontinued remedy on account of cytopenias, differentiation syndrome or QTc prolongation, Aldoss mentioned.
Unmet Want in Acute Leukemias
Aldoss famous that remedies are wanted for KMT2Ar acute leukemia, as many sufferers relapse after chemotherapy and/or HSCT, with remaining remission charges in each adults and pediatrics remaining low.
Subsequently, within the section 2 AUGMENT-101 trial, investigators evaluated the protection and efficacy of the oral, small molecule menin inhibitor.
Sufferers acquired 163 milligrams (mg) (95 mg per sq. meter) if physique weight lower than 40 kilograms) each 12 hours orally plus a powerful CYP3A4 inhibitor in 28-day cycles till lack of at the very least morphological leukemia-free state after 4 cycles, illness development or unacceptable unwanted effects.
CR and CRh charges, in addition to security and tolerability served as the first finish factors. Secondary finish factors included the speed of CRc (outlined as CR plus CRh plus CR with incomplete platelet restoration plus CR with incomplete depend restoration), ORR, DOR and time to response.
Sufferers had been eligible with the next standards: age of 30 days or extra; relapsed/refractory acute myeloid leukemia, acute lymphoblastic leukemia, or mixed-phenotype acute leukemia with KMT2Ar or NPM1m; and sufferers with main refractory or relapsed refractory illness. Sufferers had been excluded if that they had lively central nervous system illness.
Among the many sufferers within the efficacy (97 sufferers) and security (116 sufferers) analyses, median age was 37 years and 35.5 years, respectively, with the vast majority of each teams being within the age vary of 18 to 65 years (67% and 63.8%). Over half of each teams had been girls (56.7% and 57.8%, respectively) and had been White (71.1% and 69%).
In line with the summary, sufferers underwent a median of two prior therapies, with 51 (44%) receiving three or extra prior traces, 73 (63%) receiving prior Venclexta (venetoclax) and 59 (51%) who underwent prior HSCT.
Aldoss concluded by noting that the impartial NPM1m cohort outcomes from the trial will likely be introduced in future publications.
Reference:
“Up to date Outcomes and Longer Comply with-up from the AUGMENT-101 Section 2 Research of Revumenib in All Sufferers with Relapsed or Refractory (R/R) KMT2Ar Acute Leukemia” by Dr. Ibrahim Aldoss et al., introduced at: 2024 ASH Annual Assembly; Dec. 7 to 10, 2024, San Diego, California, summary 211.
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