Conference Interview #6 of 16
Liz Meszaros, MDLinx
58th American Society of Hematology Annual Meeting & Exposition
San Diego, California, United States | December 03-06, 2016
“This study is primarily directed at older AML patients, which are people aged 60 years and older. We deliberately chose this AML patient population, this age cohort, because we know when these patients go through aggressive chemotherapy, it takes a long time for the bone marrow to heal and recover. That has a lot of implications,” said lead researcher Sudipto Mukherjee, MD, PhD, MPH, assistant staff, Taussig Cancer Institute/Leukemia Program, Cleveland Clinic, Cleveland, OH.
“Delayed platelet count, in particular, could lead to prolonged dependence on platelet transfusion, there is a risk of bleeding, there could be a risk of alloimmunization to platelet transfusions, and more importantly, it may delay their time to reach complete remission, which is a gold standard to reach in a timely manner so that they can get started on subsequent chemotherapies,” he added.
Dr. Mukherjee and colleague conducted this interim, prespecified analysis of a single arm, phase 2 study in older AML patients to assess the efficacy of eltrombopag in accelerating platelet counts. They included 13 newly diagnosed AML patients aged ≥ 60 years (mean age: 64 years; 54% female), who had ECOG scores ranging from 0 to 2 (75% ECOG status 0 or 1), who had no active second malignancy, and no evidence of marrow fibrosis at the time of diagnosis. The majority of patients (62%) had de novo AML, and 38% had secondary AML.
Induction chemotherapy (IC) was comprised of either daunorubicin (45 mg/m2) or idarubicin (12 mg/m2), both anthracyclines, for 3 days and infusional cytarabine (100 mg/m2) for 7 days. Beginning on day 15, patients who had no morphologic evidence of disease by day 14, received eltrombopag, for which the criterion was marrow blasts greater than 5%.
Patients received daily doses of 200 mg eltrombopag (100 mg for East Asian patients), with a one-time maximal dose escalation to 300 mg daily (150 for East Asian patients), if platelet counts were still ≤ 50,000 µL after 2 weeks of treatment. When platelet counts exceeded 100,000 µL, eltrombopag treatment was discontinued.
Researchers used a two-stage accrual design, with a maximum goal of 31 patients, with early discontinuation if ≥ 5 of the 12 initial patients did not achieve platelet counts of ≥ 50,000 µL by day 24.
Median duration of eltrombopag treatment was 10 days, with no dose escalations required, and patients were given a median of 4 units of platelets during induction. During the treatment period, this decreased to 2 units or 1 unit every 4.8 days (P=0.04). Patients were transfused with a median of 7 units of red blood cells, or 1 unit every 2 days during induction. During treatment, however, this requirement decreased to 4 units, or 1 unit every 3.6 days (P=0.02).
A full 92% of patients achieved CR (median time: 32.5 days from IC), and 1 patient had an incomplete CR. From IC initiation, median time to platelet count ≥ 20,000 µl was 19 days, ≥ 50,000 µl 24 days, and ≥ 100,000 µL 25 days.
By day 24, 62% of patients had platelet counts ≥ 50,000 µl. Median peak platelet count was 719,000 µL, with the median time to reach peak count from eltrombopag initiation was 19 days.
All toxicities were grade 1 or 2 and included nausea, decreased vision, elevated transaminases, and hypokalemia and hypomagnesaemia.
This study met all interim objectives, and is currently accruing patients.
“Although this is an interim analysis, the data are promising. If these data hold true, it gives us an additional agent that can be used in the front-line setting with a very aggressive chemotherapy regimen in older people, and gives older people a chance to recover their counts—especially the platelet counts, in a timely manner, and proceed to subsequent treatments, be it additional chemotherapy or even proceeding to a bone marrow transplant,” said Dr. Mukherjee.
“That would really be a big change in our treatment practice, considering the fact that one of the biggest problems we face with our older AML population going through another chemotherapy, is that we just don’t get their platelet counts to recover in time to do additional treatments,” he concluded.
Dr. Mukherjee is a consultant for and has received honoraria and research funding from Celgene, Ariad, and Novartis.