A Sherban1, P Raanani2, R Gurion3, O Wolach4, A Gafter-Gvili5. 1. Internal Medicine Department A, Rabin Medical Center, Beilinson Hospital, 39 Jabotinski St., Petah Tikva, P.O BOX 49100, Israel; Sackler Faculty of Medicine, Tel Aviv University, 39 Haim Levanon St., Tel-Aviv, P.O. Box 39040, Israel. Electronic address: a.sherban@gmail.com. 2. Sackler Faculty of Medicine, Tel Aviv University, 39 Haim Levanon St., Tel-Aviv, P.O. Box 39040, Israel; Division of Hematology, Rabin Medical Center, Beilinson Hospital, 39 Jabotinsky St., Petah Tikva, P.O BOX 49100, Israel. Electronic address: praanani@012.net.il. 3. Sackler Faculty of Medicine, Tel Aviv University, 39 Haim Levanon St., Tel-Aviv, P.O. Box 39040, Israel; Division of Hematology, Rabin Medical Center, Beilinson Hospital, 39 Jabotinsky St., Petah Tikva, P.O BOX 49100, Israel. Electronic address: ronitgurion@gmail.com. 4. Sackler Faculty of Medicine, Tel Aviv University, 39 Haim Levanon St., Tel-Aviv, P.O. Box 39040, Israel; Division of Hematology, Rabin Medical Center, Beilinson Hospital, 39 Jabotinsky St., Petah Tikva, P.O BOX 49100, Israel. Electronic address: owolach@gmail.com. 5. Internal Medicine Department A, Rabin Medical Center, Beilinson Hospital, 39 Jabotinski St., Petah Tikva, P.O BOX 49100, Israel; Sackler Faculty of Medicine, Tel Aviv University, 39 Haim Levanon St., Tel-Aviv, P.O. Box 39040, Israel; Division of Hematology, Rabin Medical Center, Beilinson Hospital, 39 Jabotinsky St., Petah Tikva, P.O BOX 49100, Israel. Electronic address: gaftera@gmail.com.
Abstract
BACKGROUND: Older patients encompass about 75 % of patients with acute myeloid leukemia (AML). Today therapeutic options to prevent relapse in older patients who managed to achieve complete remission (CR) after intensive chemotherapy are scarce. Recent randomized controlled trials (RCTs) have aimed to reduce the risk of relapse by means of post-CR maintenance therapy. METHODS: We performed a systematic review and meta-analysis of RCTs comparing the efficacy and safety of maintenance with hypomethylating agents (HMA) vs. observation, conventional care or placebo in older patients with AML who are not candidates for allogeneic hematopoietic transplantation (allo-HCT). We searched Cochrane Library, PubMed and conference proceedings up to August 2021. RESULTS: Six trials were included. Treatment with hypomethylating agents significantly improved overall survival (HR 0.80, 95 % CI 0.70 to 0.91, I2 = 30 %), and disease control (HR 0.80, 95 % CI 0.70 to 0.91, I2 = 0). A significant decrease was seen in both one year mortality (Risk Ratio [RR] 0.61, 95 % CI 0.48 to 0.77, I2 = 0) and mortality at the end of follow-up (RR 0.77, 95 % CI 0.67 to 0.88, I2 = 0). The rate of relapse at 6 months and at one-two years was lower in the HMA arm vs. control (RR, 0.59; 95 % CI, 0.47-0.72; RR, 0.74, I2 = 0; 95 % CI 0.69 - 0.91, I2 = 41 %, respectively). HMA were associated with a statistically non-significant increase in the risk of serious adverse events (RR 3.44, 95 % CI 0.93-12.74, I2 = 80 %). CONCLUSIONS: Our meta-analysis shows that in older patients who are not candidates for allo-HCT, maintenance therapy with HMA improves OS and disease control without a statistically significant increase in adverse events.
BACKGROUND: Older patients encompass about 75 % of patients with acute myeloid leukemia (AML). Today therapeutic options to prevent relapse in older patients who managed to achieve complete remission (CR) after intensive chemotherapy are scarce. Recent randomized controlled trials (RCTs) have aimed to reduce the risk of relapse by means of post-CR maintenance therapy. METHODS: We performed a systematic review and meta-analysis of RCTs comparing the efficacy and safety of maintenance with hypomethylating agents (HMA) vs. observation, conventional care or placebo in older patients with AML who are not candidates for allogeneic hematopoietic transplantation (allo-HCT). We searched Cochrane Library, PubMed and conference proceedings up to August 2021. RESULTS: Six trials were included. Treatment with hypomethylating agents significantly improved overall survival (HR 0.80, 95 % CI 0.70 to 0.91, I2 = 30 %), and disease control (HR 0.80, 95 % CI 0.70 to 0.91, I2 = 0). A significant decrease was seen in both one year mortality (Risk Ratio [RR] 0.61, 95 % CI 0.48 to 0.77, I2 = 0) and mortality at the end of follow-up (RR 0.77, 95 % CI 0.67 to 0.88, I2 = 0). The rate of relapse at 6 months and at one-two years was lower in the HMA arm vs. control (RR, 0.59; 95 % CI, 0.47-0.72; RR, 0.74, I2 = 0; 95 % CI 0.69 - 0.91, I2 = 41 %, respectively). HMA were associated with a statistically non-significant increase in the risk of serious adverse events (RR 3.44, 95 % CI 0.93-12.74, I2 = 80 %). CONCLUSIONS: Our meta-analysis shows that in older patients who are not candidates for allo-HCT, maintenance therapy with HMA improves OS and disease control without a statistically significant increase in adverse events.