Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are closely intertwined diseases with poor survival rates that primarily affect older adults. The current treatment regimens are often associated with significant side effects: elderly patients often require transfusions and repeated hospitalizations for monitoring low blood counts and treating infections that arise from weakened immune systems. As a result, a substantial number of patients are unable to complete their treatment.

Investigators at the National Cancer Institute-designated Montefiore Einstein Cancer Center (MECC) have developed a new treatment protocol for patients with MDS and AML that is better tolerated than standard treatments, yet still effective. In a retrospective study published online today in Clinical Cancer Research, the MECC treatment strategy was found to be much less toxic, at least as effective as the standard chemotherapy regimen, and more convenient for patients. These findings may change the way elderly people with MDS and AML are treated.

“Our older patients struggle with the side effects brought on by standard chemotherapy, which negatively impacts their quality of life and limits time spent at home and out of the hospital,” said corresponding author Mendel Goldfinger, M.D., clinical program director of hematologic malignancies at MECC and associate professor of oncology and of medicine at Albert Einstein College of Medicine. “As is now more common for cancer treatments, we were eager to see if we could reduce the toxicity of treatment while maintaining clinical efficacy. We have developed a promising approach that we hope to confirm in a larger prospective clinical trial.”

The retrospective study assessed the outcomes for 75 patients with AML, MDS and chronic myelomonocytic leukemia (CMML) treated at MECC between November 2018 and November 2022. Thirty-nine of those patients received the MECC regimen, while the other 36 patients received the standard treatment regimen commonly used for older patients.

The standard regimen used a combination therapy: the chemotherapy drug decitabine along with the targeted agent venetoclax, which increases the efficacy of decitabine. One drug cycle consisted of giving both decitabine each day for 5 days with venetoclax given daily for at least 21 days, followed by an interruption period to allow for recovery from the toxic side effects, primarily a decrease in the bone marrow’s blood-forming activity. While venetoclax is an oral medication, decitabine is given intravenously, requiring a daily visit to an infusion center.

In the MECC regimen, a low-dose, once-weekly regimen of decitabine was given together with a once-a-week dose of venetoclax. Of note, decitabine was administered by subcutaneous injection that patients received at their local oncologist’s office, eliminating the need for daily hospital visits and making the treatment regimen much easier for patients to follow. This regimen was intended to employ the minimum dose required to suppress cancer cells without interfering with the patients’ normal blood-forming cells.

Overall, the MECC regimen was equally effective and less toxic than the standard treatment regimen. The MECC regimen had an 88% response rate (i.e., decrease or disappearance of disease) in newly diagnosed elderly AML patients, which is similar to what is observed with standard treatment outcomes. Over a median follow-up period of 260 days (nearly 9 months), patients tolerated the MECC regimen for a much longer period without interruption compared with the standard regimen: a median time on therapy of 126 days vs. 75.5 days, even though the patients in the MECC cohort were older and sicker. In addition, 47% of patients on the MECC regimen did not need a blood transfusion, while only 26% of patients on the standard regimen were able to avoid a transfusion.

The authors note that the findings should be broadly generalizable given the make-up of the patients enrolled in the study: 44% white, 32% Hispanic, and 19% Black; 60% males and 40% females.

The paper is titled “A Metabolically Optimized, Non-cytotoxic Low Dose Weekly Decitabine/Venetoclax in MDS and AML.” Other Montefiore Einstein authors include: David Levitz, M.D., Kateryna Fedorov, M.D., Lauren Shapiro, M.D., Ioannis Mantzaris, M.D., Aditi Shastri, M.B.B.S., Noah Kornblum, M.D., Alejandro Sica, M.D., Nishi Shah, M.D., Marina Konopleva, M.D., Kira Gritsman, M.D., Ira Braunschweig, M.D., Dennis Cooper, M.D., Kith Pradhan, Ph.D., Amit Verma, M.B.B.S., and Eric Feldman, M.D. Yogen Saunthararajah, M.D., is at the Cleveland Clinic. The authors declare no competing financial interests.