Case Report: Durable response to lenalidomide rechallenge after azacitidine failure in myelodysplastic neoplasm with del(5q)
Abstract
Lower-risk myelodysplastic neoplasms (MDS) with isolated del(5q) are particularly sensitive to lenalidomide, although most patients eventually lose their response and may experience disease progression. Hypomethylating agents (HMAs) are commonly used as salvage therapy after lenalidomide failure, but treatment options following subsequent HMA failure remain limited. Evidence regarding lenalidomide rechallenge after intervening HMA therapy is scarce. We report the long-term clinical course of a woman with MDS with del(5q) and multilineage dysplasia, diagnosed after prior cytotoxic therapy for colon adenocarcinoma. Lenalidomide was started for transfusion-dependent anemia (IPSS Intermediate-1; IPSS-R Intermediate) and resulted in transfusion independence and a complete cytogenetic response after four cycles. Hematologic remission was maintained for more than three years, but lenalidomide was discontinued after 41 cycles because of progressive cytopenias and cytogenetic evolution. The patient subsequently received 36 cycles of azacitidine, achieving transient hematologic improvement before disease progression with an increase in bone marrow blasts. Because the del(5q) clone persisted and no established salvage option was available, lenalidomide was reintroduced at the original starting dose and produced a rapid erythroid response together with a reduction in bone marrow blasts, without a cytogenetic response. Hematologic benefit was sustained for approximately seven years using an individualized treatment schedule. Molecular analyses performed late during the second lenalidomide course identified two pathogenic TP53 variants, at low variant allele frequency, together with a SETBP1 mutation, corresponding to a Molecular International Prognostic Scoring System (IPSS-M) High-risk category. The response was eventually lost, and transformation to acute myeloid leukemia occurred after lenalidomide discontinuation. This case illustrates that lenalidomide rechallenge may provide prolonged clinical benefit in selected patients with persistent del(5q) after progression during HMA therapy. Further studies are required to determine the frequency and biological basis of renewed lenalidomide sensitivity in this setting.
Related
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- Acquired Elliptocytosis With Hemolytic Anemia in Myelodysplastic Neoplasm With del(20q)
- Rapid Transformation of Myelodysplastic Neoplasm to Myelodysplasia-related Acute Myeloid Leukemia with Central Nervous System Leukemia in a Young Adult
- ACUTE PROMYELOCYTIC LEUKEMIA FOLLOWING MYELODYSPLASTIC NEOPLASM IN AN OCTOGENARIAN PATIENT: A CASE REPORT
- Response to Venetoclax and Azacitidine in Induction-Refractory Adult Acute Myeloid Leukemia with UBTF Tandem Duplication and Associated Aberrant Splicing: A Case Report
BibTeX
@article{sabini2026case,
title = {{Case Report: Durable response to lenalidomide rechallenge after azacitidine failure in myelodysplastic neoplasm with del(5q)}},
author = {Lorenzo Sabini and Alice Clemente and Livia Leuzzi and Giorgia Saporiti and Sara Tarantino and Stefania Girlanda and Niccolò Frungillo and Francesca Cavallaro and Marta Bruno Ventre and Fabio Serpenti and Ilaria Carola Casetti and Francesco Onida},
journal = {Frontiers in Oncology},
year = {2026},
month = nov,
doi = {10.3389/fonc.2026.1978049},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1978049},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Case Report: Durable response to lenalidomide rechallenge after azacitidine failure in myelodysplastic neoplasm with del(5q)
AU - Lorenzo Sabini
AU - Alice Clemente
AU - Livia Leuzzi
AU - Giorgia Saporiti
AU - Sara Tarantino
AU - Stefania Girlanda
AU - Niccolò Frungillo
AU - Francesca Cavallaro
AU - Marta Bruno Ventre
AU - Fabio Serpenti
AU - Ilaria Carola Casetti
AU - Francesco Onida
PY - 2026
DA - 2026/11/04
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1978049
UR - https://www.frontiersin.org/articles/10.3389/fonc.2026.1978049
AB - Lower-risk myelodysplastic neoplasms (MDS) with isolated del(5q) are particularly sensitive to lenalidomide, although most patients eventually lose their response and may experience disease progression. Hypomethylating agents (HMAs) are commonly used as salvage therapy after lenalidomide failure, but treatment options following subsequent HMA failure remain limited. Evidence regarding lenalidomide rechallenge after intervening HMA therapy is scarce. We report the long-term clinical course of a woman with MDS with del(5q) and multilineage dysplasia, diagnosed after prior cytotoxic therapy for colon adenocarcinoma. Lenalidomide was started for transfusion-dependent anemia (IPSS Intermediate-1; IPSS-R Intermediate) and resulted in transfusion independence and a complete cytogenetic response after four cycles. Hematologic remission was maintained for more than three years, but lenalidomide was discontinued after 41 cycles because of progressive cytopenias and cytogenetic evolution. The patient subsequently received 36 cycles of azacitidine, achieving transient hematologic improvement before disease progression with an increase in bone marrow blasts. Because the del(5q) clone persisted and no established salvage option was available, lenalidomide was reintroduced at the original starting dose and produced a rapid erythroid response together with a reduction in bone marrow blasts, without a cytogenetic response. Hematologic benefit was sustained for approximately seven years using an individualized treatment schedule. Molecular analyses performed late during the second lenalidomide course identified two pathogenic TP53 variants, at low variant allele frequency, together with a SETBP1 mutation, corresponding to a Molecular International Prognostic Scoring System (IPSS-M) High-risk category. The response was eventually lost, and transformation to acute myeloid leukemia occurred after lenalidomide discontinuation. This case illustrates that lenalidomide rechallenge may provide prolonged clinical benefit in selected patients with persistent del(5q) after progression during HMA therapy. Further studies are required to determine the frequency and biological basis of renewed lenalidomide sensitivity in this setting.
SN - 2234-943X
ER -