Impact of Lenalidomide Treatment on Overall Survival in Patients With Lower-Risk, Transfusion-Dependent Myelodysplastic Syndromes

Giagounidis, Aristoteles; Pelligra, C.; Franco‐Villalobos, Conrado; Tang, Derek; Morison, Jessica; Beach, C.L.; Hu, Angela; Platzbecker, Uwe; Fenaux, Pierre

doi:10.1016/j.clml.2022.05.001

Cited by 7 publications

(5 citation statements)

References 51 publications

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“…Since its serendipitous demonstration of an exceptional e cacy in MDS with del(5q) almost 20 years ago, LEN has been largely and successfully employed in the clinics with erythroid and cytogenetic response, leading to prolongation of OS (27). With its activity in promoting erythropoiesis in MDS del(5q), LEN has demonstrated an acceptable pro le of tolerability, but it is not completely devoid of toxicity.…”

Section: Discussionmentioning

confidence: 99%

Transfusion independence after lenalidomide discontinuation in patients with del(5q) myelodysplastic syndrome: a HARMONY Alliance study

Díez-Campelo,

Germing,

Bally

et al. 2024

Preprint

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Lenalidomide (LEN) can induce RBC transfusion independence (RBC-TI) in 60–70% of del(5q) myelodysplastic syndrome (MDS) patients. Current recommendation is to continue LEN in responding patients until failure or progression, with likelihood of toxicity and a high cost for healthcare systems. This HARMONY Alliance study investigated the outcome of MDS del(5q) patients who discontinued LEN in RBC-TI. We enrolled 118 patients with an IPSS-R low-intermediate risk. Seventy patients (59%) discontinued LEN for intolerance, 38 (32%) per their physician decision, nine (8%) per their own decision and one (1%) for unknown reasons. After a median follow-up of 49 months from discontinuation, 50/118 patients lost RBC-TI and 22/30 who underwent cytogenetic re-evaluation lost complete cytogenetic response. The median RBC-TI duration was 56 months. In multivariate analysis RBC-TI duration after LEN discontinuation correlated with low transfusion burden before LEN therapy, treatment ≥ 12 LEN cycles, younger age and higher Hb level at LEN withdrawal. Forty-eight patients were re-treated with LEN for loss of response and 28 achieved RBC-TI. These data show that stopping LEN therapy in MDS del(5q) patients in RBC-TI allows prolonged maintenance of TI in a large subset of patients.

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Section: Discussionmentioning

confidence: 99%

Transfusion independence after lenalidomide discontinuation in patients with del(5q) myelodysplastic syndrome: a HARMONY Alliance study

Díez-Campelo,

Germing,

Bally

et al. 2024

Preprint

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“…The growing body of mechanistic data in concert with the positive results of the prospective TELESTO study of oral iron chelation in lower risk MDS, as well as multiple retrospective datasets all point towards a positive impact for iron chelation on outcome for patients [25,26]. In my view, a preponderance of the data suggest that our interventions are in fact occurring too late, and perhaps that earlier intervention with growth factors and iron chelation, prior to the development of overt iron overload, may be needed to help mitigate the impact of disordered iron homeostasis in patients with MDS [27,28,29 ▪ ,30 ▪▪ ,31 ▪▪ ].…”

Section: Iron Homeostasismentioning

confidence: 92%

“…For many years, only limited therapeutic options were available for lower risk MDS patients with anemia. Erythropoiesis-stimulating agents (ESA) have been the mainstay of therapy for anemic low risk patients, with lenalidomide for MDS-del5q and select additional individuals [30 ▪▪ ,42]. Best responses to both these drug classes are predicted in those with lower-risk disease, who are not heavily transfusion dependent (<4 U/8 weeks) and who have lower endogenous EPO levels (<200–500 U/l) [28,42].…”

Section: Terminal Differentiationmentioning

confidence: 99%

Transfusion avoidance in myelodysplastic neoplasms

Griffiths

2023

Current Opinion in Hematology

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Purpose of review Myelodysplastic neoplasms (MDS) are diseases of stem cell aging associated with complications from inadequate hematopoiesis (red cells, neutrophils and platelets) and variable risk for transformation to acute myeloid leukemia. Those with low-risk disease also suffer and die from MDS-related complications. Among the most challenging is development of anemia and transfusion dependence, which impacts quality of life and is associated with reduced survival. Appreciating and measuring the quality-of-life impact, preventing (if possible), treating, and managing the complications from anemia in MDS are of critical importance. Recent findings Recent developments in basic science highlight the potential deleterious impact of iron overload within the developing red cell niche. Iron overload can compromise red cell maturation from healthy as well as malignant clones and produces an environment favoring expansion of mutant clonal cells, potentially driving disease progression. Observational studies in nontransfusion dependent MDS highlight that iron overload occurs even in the nontransfusion dependent. The newly approved (and established) therapies for management of MDS-related anemia work best when begun before patients become heavily transfusion-dependent. Summary Iron overload is detrimental to hematopoiesis. Understanding the benefit afforded by transfusion is critical to optimal application and patient reported outcomes can inform this. Recently developed therapies are active and optimized application may improve response.

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“…The potential rescue role of lenalidomide in EPO-failed non-del (5q) MDS patients has been explored, reporting in [91] the achievement of transfusion independence longer than 8 weeks in 26.9% of patients, achieving the response within 16 weeks of treatment [91]. Notably, these responses impacted OS by the reduction of transfusion burden and ferritin levels [92]. Furthermore, in the lenalidomide-treated patients, the presence of a mutation in any five gene, such as ASXL1, ETV6, EZH2, RUNX1, and TP53, was associated with a significantly shorter median OS, whereas those involving SF3B1, TET2, and DNMT3A had no significant effect on the patient's outcome [93].…”

Section: Lower-risk Mdsmentioning

confidence: 99%

Latest Insights and Therapeutic Advances in Myelodysplastic Neoplasms

Niscola,

Gianfelici,

Giovannini

et al. 2024

Cancers

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Myelodysplastic syndromes/neoplasms (MDSs) encompass a range of hematopoietic malignancies, commonly affecting elderly individuals. Molecular alterations in the hematopoietic stem cell compartment drive disease pathogenesis. Recent advancements in genomic profiling have provided valuable insights into the biological underpinnings of MDSs and have expanded therapeutic options, particularly for specific molecularly defined subgroups. This review highlights the diagnostic principles, classification updates, prognostic stratification systems, and novel treatments, which could inform future clinical trials and enhance the management of adult MDS patients, particularly for specific molecularly defined subgroups.

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Impact of Lenalidomide Treatment on Overall Survival in Patients With Lower-Risk, Transfusion-Dependent Myelodysplastic Syndromes

Cited by 7 publications

References 51 publications

Transfusion independence after lenalidomide discontinuation in patients with del(5q) myelodysplastic syndrome: a HARMONY Alliance study

Transfusion independence after lenalidomide discontinuation in patients with del(5q) myelodysplastic syndrome: a HARMONY Alliance study

Transfusion avoidance in myelodysplastic neoplasms

Latest Insights and Therapeutic Advances in Myelodysplastic Neoplasms

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