Click Here to
Subscribe
Breaking
News, Updates,
& More
Stay Up
to Date

Safety and Tolerability of Midostaurin from Expanded Treatment Protocol in Patients with FLT3 Mutation–Positive, Newly Diagnosed AML

JHOP - March 2018 Vol 8, No 1 - ASH

 

 

Midostaurin, a multikinase inhibitor targeting FLT3 and KIT, is indicated for the treatment of patients with newly diagnosed, FLT3 mutation–positive acute myeloid leukemia (AML) in combination with standard induction and consolidation chemotherapy, based on demonstrations of superior survival outcomes versus placebo in the randomized, double-blind, phase 3 RATIFY trial. The Radius-X open-label expanded treatment protocol (ETP) was designed to provide access to midostaurin and obtain additional insights into the safety and tolerability profile of midostaurin in adult patients with newly diagnosed, FLT3 mutation–positive AML.

Patients eligible for enrollment into the ETP were adults with newly diagnosed, FLT3 mutation–positive AML (internal tandem duplication [ITD] or tyrosine kinase domain [TKD]) who were fit to receive intensive induction and consolidation chemotherapy. Patients received 1 to 2 cycles of induction therapy (cytarabine plus daunorubicin or idarubicin) and ≤4 cycles of cytarabine consolidation therapy in combination with midostaurin (50 mg twice daily on days 8-21 of each 28-day cycle), followed by ≤12 months of single-agent midostaurin (50 mg twice daily on days 1-28). Patients could initiate midostaurin therapy at any point during standard chemotherapy prior to the completion of a second cycle of consolidation.

At data cutoff, 103 patients were enrolled in the study, including 47 (46%) patients enrolled during induction and 56 (54%) during consolidation. Overall, 31 patients went on to receive maintenance therapy, 12 of whom remain on therapy. A total of 85 (83%) patients discontinued the study, mostly due to transplant (n = 52), adverse events (AEs; n = 7), relapse (n = 12), and not achieving complete response (CR)/CR with incomplete hematologic recovery (CRi; n = 4). Among the FLT3 mutation–positive patients, 75 had ITD mutations and 23 had TKD. The median age was 58 years (range, 19-79 years); 45% of patients were aged ≥60 years. The median duration of midostaurin exposure was 29 days (range, 3-299 days); dose adjustments were needed in 42 patients.

The majority (99%) of patients experienced ≥1 any-grade AEs that occurred mostly during induction (94%) and/or consolidation (85%). Grade 3/4 AEs were reported in 82% of patients. The most common any-grade nonhematologic AEs, occurring in ≥20% of patients, were nausea, diarrhea, anemia, fatigue, vomiting, headache, hypokalemia, and constipation; these were generally comparable between patients that received idarubicin and daunorubicin induction chemotherapy. Serious AEs were reported in 51% of patients, including febrile neutropenia (35%), cellulitis (6%), and pancytopenia. Eleven events of increases in corrected QT (QTc) intervals >30 ms occurred in 6 patients, none of which were >500 ms or considered clinically significant events. Midostaurin dose reduction to 50 mg once daily normalized the QTc intervals. Serious AEs were reported in 46% of patients, febrile neutropenia being the most common (32%).

Among the 47 patients who received midostaurin therapy during induction, 35 patients (74%) achieved a CR or a CRi. Among the 85 patients who received midostaurin during consolidation therapy, 52 patients (61%) remained in CR/CRi.

These results of the Radius-X ETP showed that the safety profile of midostaurin was consistent with that previously described in the pivotal phase 3 RATIFY trial.


Reference

  1. Roboz G, et al. 2017 ASH. Abstract 1338.
Related Items
Checkpoint Inhibition Consolidation Therapy Promising in High-Risk Hematologic Malignancies
Charles Bankhead
JHOP - March 2019 Vol 9, No 1 published on March 13, 2019 in ASH
MURANO: Venetoclax-Rituximab at Fixed Duration Beats Chemo­immunotherapy in Relapsed/Refractory CLL
Phoebe Starr
JHOP - March 2019 Vol 9, No 1 published on March 13, 2019 in ASH
Researchers Identify First Mutation to Explain Resistance to Venetoclax
Phoebe Starr
JHOP - March 2019 Vol 9, No 1 published on March 13, 2019 in ASH
Checkpoint Inhibitor a New Approach to Jump-Start a Waning Response to CAR T-Cell Therapy
Phoebe Starr
JHOP - March 2019 Vol 9, No 1 published on March 13, 2019 in Immunotherapy, ASH
Durable Responses to CAR T-Cell Therapy in B-Cell Lymphomas
Phoebe Starr
JHOP - March 2019 Vol 9, No 1 published on March 13, 2019 in Lymphoma, ASH
First-Line Ibrutinib Improves Outcomes Compared with Current Standard of Care in Older Patients with CLL
Wayne Kuznar
JHOP - March 2019 Vol 9, No 1 published on March 13, 2019 in Leukemia, ASH
Palliative Care Use Dismal Among Patients with Hematologic Malignancies
TON - March 2018, Vol 11, No 1 published on March 9, 2018 in Conference Correspondent, ASH, Palliative Care, Hematologic Cancers
Oral Multiple Myeloma Medication Linked to Decreased Productivity Loss
Chase Doyle
TON - March 2018, Vol 11, No 1 published on March 9, 2018 in Conference Correspondent, ASH, Multiple Myeloma
Ivosidenib, New IDH1 Inhibitor, Elicits Complete Response in Relapsed Acute Myeloid Leukemia
Wayne Kuznar
TON - March 2018, Vol 11, No 1 published on March 9, 2018 in Conference Correspondent, Drug Updates, ASH
Impact of Pharmacist-Driven Educational Intervention on Documentation of Bowel Function Assessment in Patients with Cancer Who Are Using Opioids
Kimberly N. Flynn, PharmD, BCPS, Celestine Gochett, PhD, AOCNS
JHOP - March 2018 Vol 8, No 1 published on March 1, 2018 in Original Research, ASH
Last modified: March 14, 2018