ASH 2023 Highlight 1

The first daily highlight on ASH 2023 is done by Dr Bert Heyrman, haematologist at the ZNA Hospitals, Antwerp.  He selected 4 presentations from the session on Myeloid Malignancies: Real-World Treatment Patterns and Outcomes.

Hypomethylating agents (HMAs) represent the established therapeutic standard for individuals afflicted with higher-risk myelodysplastic syndromes (HR-MDS). Dr. Zeidan presented real-life data on the use of oral decitabine, in conjunction with a decitabine inhibitor, relative to intravenous (IV) and subcutaneous (SC) formulations, predominantly encompassing decitabine and azacitidine. Despite lacking approval in Belgium, the oral combination of decitabine and cedazuridine (DEC-C) obtained FDA endorsement in July 2020 for MDS treatment. Real-world data trends underscore an increasing utilization of oral DEC-C, indicative of a shifting treatment landscape. During the early phases of therapy there’s an initial equivalence in treatment persistence between DEC-C and IV/SC HMAs. An improved persistence is evident with oral DEC-C, particularly extending beyond the 6-month threshold. Oral DEC-C is correlated with a significantly reduced therapeutic burden for the patient.

Dr. Herrera delved into the intricate interplay between MDS, cardiovascular disease (CVD) and the potential mitigating effects of HMA therapy. He had previously demonstrated that MDS is independently associated with an increased risk of CVD in older patients. Approximately 25% of MDS patients reportedly die from CVD, with a plausible mechanism involving CH-mediated accelerated atherosclerosis attributed to inflammatory vascular responses. The central hypothesis of his presentation postulated that HMA therapy could potentially diminish the risk of CVD by addressing clonal hematopoiesis and mitigating inflammation. An extensive analysis of the SEER database comprising more than 14,000 patients revealed no significant association between HMAs and a reduction in the risk of CVD among MDS patients. As such, follow-up assessments specifically focused on CVD remain necessary, even when MDS patients exhibit favourable haematological responses.

In a retrospective analysis conducted by Dr. Alice Mims, an Electronic Medical Record (EMR) database was scrutinized to compare the outcomes of two treatment regimens for patients with newly diagnosed acute myeloid leukemia (AML). The study juxtaposed the efficacy of intensive chemotherapy followed by oral azacitidine (Oral-AZA) maintenance treatment against the regimen of venetoclax plus injectable azacitidine (VEN-AZA). Patients treated with frontline intensive chemotherapy followed by Oral-AZA maintenance had significantly better survival outcomes than patients who were treated and achieved remission with VEN-AZA. These results suggest that patients with newly diagnosed AML eligible for frontline intensive chemotherapy should receive this regimen, followed by Oral-AZA maintenance, if they are transplant-ineligible at remission. Unfortunately, the Oral-AZA maintenance treatment is not yet available in Belgium.

The last presentation of this session was on real-life data in primary myelofibrosis (PMF). Notably, the introduction of ruxolitinib (Rux) has demonstrated enhanced survival rates; however, concerns have arisen regarding potential cardiotoxic effects associated with the medication. Given the prolonged exposure of patients to Rux, there is an increasing need for diligent CVD monitoring. A retrospective study of patients diagnosed with PMF between 2003 and 2019 was conducted. The period was split into the pre-Rux (2003-2010) and post-approval Rux eras (2012-2019) and compared the standard mortality ratios (SMRs) of CVD in both periods. The risk of CVM in PMF relative to the general population did not reveal an apparent increase in the era after the approval of Rux. On the contrary, the period following the introduction of Rux demonstrated an association with reduced deaths from CVD. Further studies are needed to examine and validate this observation.

References:

Zeidan AM, ASH 2023, #548

Herrera DA, ASH 2023, #549

Mims A, ASH 2023, #550

Ilerhunmwuwa NP, ASH 2023, #552

With the educational support of: