Mobilization-Driven Postconsolidation Therapy in Elderly Patients with Acute Myeloid Leukemia: Feasibility and Efficacy of Autologous Stem Cell Transplantation versus Low-Dose Gemtuzumab Ozogamicin

Abstract

We prospectively evaluated 2 postconsolidation strategies, administered according to the mobilization outcome, in 72 acute myeloid leukemia (AML) fit elderly patients, achieving complete remission after the first high-dose cytarabine-based induction. Autologous stem cell transplantation (ASCT) was performed in patients collecting ≥3 × 10(6) CD34(+)/kg and low-dose gemtuzumab ozogamicin (GO) was performed in poor mobilizers (collecting <3 × 10(6) CD34(+)/kg). Fifty-five patients (76.3%) underwent peripheral blood stem cell (PBSC) mobilization, after first consolidation, and 24 of 55 (44%) collected >3 × 10(6) CD34(+) cells/kg. Among the 55 patients eligible for PBSC mobilization, 7 did not receive the planned treatment, 23 were allocated for ASCT, and 25 were allocated for GO on an intention-to-treat basis. With a median follow-up of 70 months (range, 24 to 124), 20 of 55 patients are alive, 18 of them in continuous complete remission. The 8-year overall survival (OS) and disease-free survival (DFS) are, respectively, 35.9% (95% confidence interval [CI] 24% to 49.8%) and 31.2% (95% CI, 21% to 43.8%), median OS and DFS were 22 and 16 months, respectively. In multivariate analysis, postconsolidation treatment and hyperleukocytosis (WBC > 50,000/μL) significantly predicted OS and DFS, whereas secondary AML was significantly associated with a higher relapse rate (83.4% versus 54% of de novo AML). Patients with hyperleukocytosis had 0% 3-year OS versus the 46% (at 8 years) in patients without hyperleukocytosis (P = .01); 57% of patients in the GO arm are alive at 8 years, compared with 25.4% of patients in the ASCT arm, who had an overall relative risk (RR) of death of 2.6 (95% CI, 1.2 to 5.8; P = .02). DFS at 8 years was 45.3% in patients receiving GO, compared with 26% in ASCT arm (RR, 2.1; 95% CI, 1 to 4.3; P = .05). Our study outlines low feasibility and efficacy of ASCT in elderly AML patients, whereas postconsolidation with GO appears safe and effective in this unfavorable setting. The study was registered at Umin Clinical Trial Registry (www.umin.ac.jp/ctr), number R000014052.

American Society of Hematology 2020 guidelines for treating newly diagnosed acute myeloid leukemia in older adults

“…139 In 1 observational study, researchers reported the outcomes for 48 patients who received 1 cycle of consolidation plus 1 cycle of postremission therapy with gemtuzumab ozogamicin or 1 cycle of consolidation therapy plus autologous HSCT (auto-HSCT; evidence profile 2). 140 In 4 studies, 3 RCTs with 258 participants 70,141,142 and 1 observational study with 126 patients, 106 researchers compared mortality and time to recurrence between patients who received 2 cycles of consolidation therapy and patients who received 1 cycle (evidence profile 3).…”

Feasibility and Outcome of a Phase II Study of Intensive Induction Chemotherapy in 91 Elderly Patients with AML Evaluated Using a Simplified Multidimensional Geriatric Assessment

“…One is still in second CR, and the other two eventually relapsed after retreatment with GO. The 8-year OS, DFS and EFS were respectively 20.4% (11.1-34.8%), 22.9% (14.5-34.2%) and 17.9% (11.3-27.2) ( Fig. 1a).…”

“…Poor mobilizers and patients ineligible for ASCT for other reasons received gemtuzumab ozogamicin (GO) consolidation of 3 monthly 3 mg/m 2 i.v. infusions followed by three further courses every 3 months as previously described [22]. Relapsed patients received a second-line chemotherapy at the clinician's discretion.…”

Autologous Hematopoietic Stem Cell Transplantation in Acute Myelogenous Leukemia

“…Therefore, the number of infused CD34 + cells is a key factor affecting hematopoietic reconstitution and outcomes after ASCT. In a phase II prospective study in patients with AML in CR1, autografted patients who received >7.1 £ 10 6 /kg CD34 + cells showed poor OS [64]. In a separate study, higher yields of CD34 + cells (7 £ 10 6 /kg) were associated with an inferior prognosis owing to a significantly higher RR [65].…”