Long‐term efficacy and safety of arsenic trioxide for first‐line treatment of elderly patients with newly diagnosed acute promyelocytic leukemia

Abstract

BACKGROUND:The prognosis of acute promyelocytic leukemia (APL) in the elderly is poorer than that of younger patients after treatment with all-trans retinoic acid plus chemotherapy, which is the current standard therapy for APL. A significantly higher mortality during consolidation therapy was found, which is mainly due to deaths from sepsis following chemotherapy-induced myelosuppression. METHODS: A total of 33 patients aged 60 years or older with de novo APL were treated with single-agent arsenic trioxide (ATO) for remission induction and postremission therapy. The postremission therapy continued for up to 4 years. RESULTS: Twentynine patients (87.9%) achieved a hematologic complete remission, and the most common adverse event during remission induction was leukocytosis (63.6%). Definite differentiation syndrome was observed in 5 patients. Nonhematologic adverse events were all manageable and reversible. Twenty-eight patients proceeded to postremission therapy. Adverse effects during postremission therapy were mild, transient, and no treatment was required. No patients died from ATO-related toxicities. With a median follow-up of 99 months, the 10-year cumulative incidence of relapse, overall survival, disease-free survival, and cause-specific survival were 10.3%, 69.3%, 64.8%, and 84.8%, respectively, which are comparable with those in the younger APL partners. No significant risks for development of chronic arsenicosis or second malignancy were observed during the follow-up period. CONCLUSIONS: The results indicate that the single-agent ATO regimen is safe and effective with long-term durable remission, and could be used as first-line treatment

Acute promyelocytic leukemia in patients aged >70 years: the cure beyond the age

“…The introduction of newer and less toxic agents in the treatment of APL (arsenic trioxide and gentuzumab ozogamicin) will probably improve these results [18][19][20][21], allowing a better tolerance and a stronger intensity in this particular subset of frailer patients.…”

New Strategies in Acute Promyelocytic Leukemia: Moving to an Entirely Oral, Chemotherapy-Free Upfront Management Approach

“…Two prospective studies of ATO monotherapy for newly diagnosed APL reported 5-year event-free survival (EFS), disease-free survival (DFS), and OS rates of 69%, 80% and 67%, and 74% and 64%, respectively (31, 34). ATO-associated toxicities, mainly cytopenias, liver enzyme abnormalities, QTc prolongation, and differentiation syndrome, were generally manageable and reversible (31, 34, 35). Arsenic directly binds to the PML moiety and exhibits dose-dependent dual effects with preferential a proapoptotic effect at higher concentrations and partial differentiation at lower concentrations (Fig.…”

ATO/ATRA/Anthracycline-Chemotherapy Sequential Consolidation Achieves Long-Term Efficacy in Primary Acute Promyelocytic Leukemia

“…The reason might be that majority of the relapsed patients lost sensitivity to ATRA due to previous exposure, making it difficult to expect a full efficacy of the synergism between ATRA and ATO in those patients. In addition, parts of recent studies about different risks of patients were summarized in Table 3 [23], [25], [31], [37]–[42] to make a comparison and we found that there was no strong evidence about the recommended strategy for different risk groups. However, the addition of ATO was proved to improve the long-term survival of patients with different risks, which gave support to our present study.…”