EXPERIENCE OF GLASDEGIB IN PATIENTS WITH ELDERLY ACUTE MYELOID LEUKEMIA

Abstract

Aim: Acute myeloid leukemia (AML) is characterized by the increase of high levels of myeloid cells in the bone marrow. In general, AML is a disease of older adults. Many adults with AML are unable to receive intensive chemotherapy because of its toxicity.In this study, it was aimed to retrospectively evaluate patients with AML who were treated Glasdegib-based regimens in our center.Case 1: A 75-year-old male patient was diagnosed with congestive heart failure + AML, and idarubicin and cytarabine chemotherapy protocol was started. The patient started to receive covid treatment due to covid lung involvement. The patient, whose treatment was interrupted for 1 month, received the second course as LDAC + glasdegib. In the bone marrow biopsy performed after the 5th cycle, it is observed in remission.Case 2: An 82-year-old male patient was diagnosed with chronic renal failure. With a diagnosis of AML intermediate risk LDAC+glasdegib treatment was given to the patient who did not go into remission after 4 cycles of decitabine treatment. The patient, who was followed in remission after 4 cycles, died due to pneumonia.Case 3: A 76-year-old male patient has a diagnosis of cerebrovascular disease. The patient, who was followed up in remission after 2 courses of azacitidine with a diagnosis of medium risk AML, was approved for glasdegib in the 3rd course of treatment, and he is being followed up with the 3rd course of LDAC+glasdegib therapy. Material and method: The data of the patients who were treated Glasdegib-based regimens with the diagnosis of AML in the Bozyaka Training and Research Hospital Department of Hematology were scanned retrospectively from their files. Results: In our 3 patients, 1 person died due to pneumonia, but the patient was being followed in remission. Our other 2 patients are still being actively followed up with LDAC + glasdegib treatments. Discussion: In 2018, the FDA approved glasdegib, a Hedgehog signaling pathway inhibitor, in adults 75 years of age or older with a diagnosis of AML or those with comorbidities that preclude the use of low-dose cytarabine plus intensive induction chemotherapy. Approval is based on interim results from the phase 2 BRIGHT 1003 study evaluating glasdegib in combination with LDAC or LDAC alone. The median OS was 4.9 months for LDAC versus 8.8 months in patients treated with glasdegib+LDAC. This difference represented an approximately 50% reduction in mortality in patients treated with glasdegib+LDAC.The final result of the BRIGHT 1003 study confirmed that glasdegib LDAC significantly improved OS compared to LDAC alone (hazard ratio, 0.495 [95% CI, 0.325-0.752]; P =0.0004). Also, the addition of glasdegib to LDAC did not cause a significant increase in adverse events.