medwireNews: European researchers reject the use of a fixed dose of low molecular weight heparin (LMWH) in patients undergoing remission-induction treatment for acute lymphoblastic leukemia or lymphoma (ALL).
The prospective side study of the HOVON-100 trial showed no significant difference in the rate of venous thromboembolism (VTE) in the first 60 days of follow-up for the patients who were given an intermediate dose of LMWH and those given no thromboprophylaxis.
Presenting the research at the EHA2024 Hybrid Congress in Madrid, Spain, Mandy Lauw (Erasmus Medical Center, Rotterdam, the Netherlands) explained that although ALL survival has improved over the past 20 years, symptomatic VTE occurs in 10–40% of patients, triggered by a combination of prothrombotic changes associated with ALL and the effect of asparaginase therapy on the coagulation system.
VTE requires therapeutic anticoagulation and interruption of ALL treatment, with an associated impact on morbidity and long-term survival, and there is “no consensus” or “global standard of care” on thromboprophylaxis in patients with ALL, Lauw said. Research has not supported the use of fresh frozen plasma, antithrombin concentrate, or the direct oral anticoagulant apixaban in this population, although LMWH has been indicated in children without increasing the risk for major bleeding, she explained.
To determine whether LMWH prophylaxis may benefit adults with ALL, the team amended the protocol of the HOVON-100 ALL trial, which investigated the addition of clofarabine to induction therapy for adults aged 18–70 years with a new diagnosis of ALL. This allowed the inclusion of a single-arm side study assessing the use of a fixed, intermediate dose of the LMWH nadroparin (5700 anti-Xa IU/day) from prephase day 1 to day 35 of induction therapy.
The per protocol primary outcome of a first episode of venous or arterial thrombosis over the first 60 days of ALL therapy occurred in 17% of the 253 patients who received LMWH versus 11% of the 116 patients who were treated before the amendment, giving a nonsignificant subdistribution hazard ratio (SHR) of 1.52 after adjusting for age group, ALL subtype, and receipt of clorafabine.
Lauw highlighted that the patients were evenly split between those aged 18–40 years and those aged over 40 years in both the LMWH (51 vs 49%) and no LMWH (42 vs 58%) groups, recognizing that only the younger cohorts received pegylated asparaginase in their first induction cycle.
Patients in the younger age group had a trend toward a lower rate of VTE with LMWH, while the opposite was seen in the older age group, with SHRs of 0.88 and 2.47, respectively, Lauw reported.
Over the full HOVON-100 trial treatment period – a median follow-up of 87 months – there was again no significant difference in the rate of first VTE events in patients who were and were not given LMWH (33 vs 22%, adjusted SHR=1.59). And there was no difference in the rate between the younger and older patients (adjusted SHR=1.59 and 1.60, respectively).
Mandy Lauw summarized that the fixed intermediate dose of LMWH did not reduce the risk of VTE and “may be disadvantageous in older patients” who are not given pegylated asparaginase in the first induction cycle.
Given the cumulative incidence of VTE in the first 60 days of treatment was 15.0%, increasing to 29.8% over the full study period, the presenter emphasized the “need for future and possibly randomized trials on VTE prevention in ALL,” including the use of alternative types of anticoagulants in this population.
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