Optimizing Treatment Strategies for Extramedullary AML

New research suggests venetoclax-containing regimens with intensive treatment and allogeneic hematopoietic stem cell transplantation (HSCT) may improve outcomes for patients with extramedullary acute myeloid leukemia (AML).

Aleksina Shatilova, MD, of the Personalized Medicine Centre at the Almazov National Medical Research Centre in Saint Petersburg, Russia, and colleagues conducted the research and presented their findings at the 10th Annual Meeting of the Society of Hematologic Oncology.

Dr. Shatilova and colleagues conducted the study because the “optimal treatment strategy for patients with extramedullary [AML] is questionable, especially as applied to extramedullary tumor persistence while bone marrow response is achieved,” they wrote.

The study included 27 patients with verified extramedullary AML, with slightly more patients being male (51.8%) than female. The median patient age was 40 years (range, 13 to 84 years). Over half of patients (55.6%) were considered adverse risk based on the 2017 European LeukemiaNet risk stratification system, while 25.9% were considered intermediate risk, and 18.5% were considered favorable risk.

All patients received standard high-intensity and low-intensity chemotherapy regimens, with 37% of patients receiving venetoclax with 5-azacytidine because they had comorbidities or refractory disease. Most patients (63%) underwent allogeneic HSCT.

Nearly three-quarters of patients (70%) who received venetoclax with 5-azacytidine had a response, with complete eradication of the extramedullary tumor reported in 50% of patients.

High-dose cytarabine “enabled eradication of extramedullary lesions in case of failure of standard and low-intensity regimens” and decreased the rate of relapse during the first year after transplant, according to the researchers. However, persistent extramedullary disease after high-dose cytarabine occurred in three of the five patients who had complete eradication of their extramedullary tumor.

Bone marrow remission occurred in 100% of patients with favorable genetic alterations, while it was only reported in 44% of patients who did not have favorable genetic alterations (P=.044). However, there was no significant difference in the complete extramedullary response rate between patients with and without favorable genetic alterations (75% and 68%, respectively; P>.05).

Patients who underwent allogeneic HSCT in their first complete remission (CR) had a reduced risk of early relapse (12%) compared with patients who received a transplant in their second or subsequent CR. (80%; P=.015).

The median overall survival was roughly five times longer in patients who received allogeneic HSCT in their first CR (38.85 months) than those who received a transplant in their second or subsequent CR (7.57 months, P=.013).

The median relapse-free survival was around 10 times longer in patients who received allogeneic HSCT in their first CR (38.85 months) than those who received a transplant in their second or subsequent CR (3.78 months, P=.0021).

“Favorable genetic aberrations do not increase the frequency of extramedullary response. Intensive treatment helps to achieve complete eradication of extramedullary tumor and reduces early relapse rate,” Dr. Shatilova and colleagues concluded. “Using [venetoclax with 5-azacytidine] is effective among patients with [extramedullary] AML, including patients who were refractory to intensive treatment, and allows complete response achievement before [allogeneic] HSCT. The best time to perform the [allogeneic] HSCT among patients with [extramedullary] AML is the first complete remission.”

Reference

Shatilova A, Budaeva I, Motorin D, et al. Venetoclax-containing regimens improve outcomes of intensive treatment and allogeneic hematopoietic stem cell transplantation in patients with extramedullary acute myeloid leukemia. Abstract #AML-396. Presented at the 10th Annual Meeting of the Society of Hematologic Oncology, September 28-October 1, 2022.