Subgroup of Elderly Patients With Acute Myeloid Leukemia May Benefit From Initial Intensive Induction Chemotherapy
Initial intensive induction chemotherapy may be of benefit in a subgroup of newly diagnosed elderly patients with acute myeloid leukemia (AML), according to a study by Ross et al in Oncology Research. However, relapse rates remained high.
Elderly patients with AML generally experience worse outcomes compared with younger patients, due in part to the higher incidence of comorbidities, reduced tolerance to standard therapy, and decreased performance status in these patients. To achieve higher complete remission rates, researchers have recently centered on attempting to determine whether elderly patients with AML can tolerate more intensive chemotherapy.
Thus, Ross and colleagues conducted a prospective study examining the efficacy and safety associated with intensive chemotherapy in patients 70 years of age or older with newly diagnosed AML. In addition, they attempted to identify factors that may be predictive of a positive response to induction chemotherapy.
Study Details
Included in the study were 62 patients (37 male and 25 female) aged ≥ 70 years with AML. Induction chemotherapy consisted of cytarabine 100 mg/m2/d on days 1 to 7 and idarubicin 12 mg/m2/d on days 1 to 3 for 54 patients, and mitoxantrone 10 mg/m2/d days 1 to 5 and etoposide 100 mg/m2/d on days 1 to 5 for the remaining 8 patients. Patients with residual leukemia received additional intensive chemotherapy (mitoxantrone and etoposide, topotecan and cytarabine, mitoxantrone and cytarabine, or idarubicin and cytarabine). Third-line therapy consisted of fludarabine and cytarabine or gemtuzumab ozogamicin (Mylotarg) and cytarabine.
The median age of patients was 73, and 32% had secondary AML. Patients were stratified by cytogenetic risk category at diagnosis, with 26% categorized as unfavorable, 60% as intermediate, 5% as favorable, and 9% were not reported.
Complete remission was defined by the presence of less than 5% blasts in the bone marrow, absence of extramedullary leukemia, and peripheral blood cell count recovery with a neutrophil count of at least 1×109/L. Overall survival was defined as the date of starting induction chemotherapy until the date of recorded death.
Overall Complete Response Rate of 56%
The overall complete response rate in these patients was 56%. Twenty-four patients achieved remission after one course of intensive chemotherapy, 10 patients after two courses, and 1 patient after three courses. Twenty-one patients (34%) had persistent leukemia after one to three courses of intensive chemotherapy. The majority of patients who achieved remission received additional postremission therapy with cytarabine.
At the time of analysis, 57 of the 62 patients studied had died. The median overall survival was 6.85 months (95% confidence interval [CI] = 3.7–13.5 months). The median overall survival for patients who achieved remission after induction chemotherapy was significantly higher than those who did not respond to therapy (20.4 months vs 3.5 months, P < .001).
Patients with intermediate or favorable cytogenetics (P = .0036) and primary AML (P = .0212) experienced higher rates of complete remission than did those with unfavorable cytogenetic profiles or secondary AML. Unfavorable cytogenetics (P = .004) and persistent leukemia after induction therapy (P < .001) were associated with lower overall survival.
The all-cause 4-week mortality rate was 11%, and the all-cause 8-week mortality rate was 17.7%, with infectious complications being the most common cause of death. All patients developed grade 4 neutropenia and thrombocytopenia, all patients had febrile neutropenia, 10 patients developed Clostridium difficile colitis, and 24 patients had bacteremia.
Closing Thoughts
Regarding predictive factors, adverse cytogenetics and secondary acute myeloid leukemia were found to influence outcomes. The researchers noted there was a significant survival benefit in patients who achieved complete remission, suggesting that this could be a prerequisite for long-term survival.
The investigators concluded, “[A] subgroup of elderly patients may benefit more from initial intensive induction chemotherapy, specifically those with [a performance status] able to tolerate induction chemotherapy and favorable cytogenetic status. However, despite high rates of initial [complete remission], relapse rates are still high, suggesting that alternative strategies of post-remission therapy are warranted.”
Michael Boyiadzis, MD, MHSc, of the University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, is the corresponding author of this article in Oncology Research. The authors reported no potential conflicts of interest.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
