Use of pembrolizumab in MSI-high uterine leiomyosarcoma; a case report and review of the literature

Wang, Yannan J.; Williams, Heather; Brzezinska, Bogna; Gaidis, Anna; Patel, Bhavi; Munroe, Janet; White, Joseph; Rungruang, Bunja

doi:10.1016/j.gore.2021.100701

Cited by 11 publications

(10 citation statements)

References 10 publications

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“…However, TMB is not indicative of response across all cancer types [86], and "TMB high" cut-offs vary widely [87]. Moreover, as mentioned previously, some success with immunotherapy in uLMS has been observed [62,63,66].…”

Section: Genomic Landscapementioning

confidence: 94%

“…PD-L1 expression, widely used as a biomarker to indicate immunotherapy response, has been reported as being positive in up to 70% of uLMS cases [61]. Two case studies involving patients with metastatic uLMS reported dramatic reductions in tumour burden and symptomatic disease with immune checkpoint inhibitor therapy [62,63], yet clinical trials on small patient cohorts have as yet failed to show any response to anti PD-1 therapy in uLMS [64,65]. However, in a basket study of doublet immunotherapy involving nivolumab and ipilimumab for four cycles followed by maintenance nivolumab [66], two patients had complete response and a third showed a partial response out of the five uLMS patients enrolled.…”

Section: Treatmentmentioning

confidence: 99%

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Interrogating the Genomic Landscape of Uterine Leiomyosarcoma: A Potential for Patient Benefit

Dall

Hamilton

Ratnayake

et al. 2022

Cancers

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Uterine leiomyosarcoma (uLMS) is a rare and aggressive gynaecological malignancy. Surgical removal and chemotherapy are commonly used to treat uLMS, but recurrence rates are high. Over the last few decades, clarification of the genomic landscape of uLMS has revealed a number of recurring mutations, including TP53, RB1, ATRX, PTEN, and MED12. Such genomic aberrations are difficult to target therapeutically or are actively targeted in other malignancies, and their potential as targets for the treatment of uLMS remains largely unexplored. Recent identification of deficiencies in homologous recombination in a minority of these tumours, however, has provided a rationale for investigation of PARP inhibitors in this sub-set. Here, we review these mutations and the evidence for therapeutic avenues that may be applied in uLMS. We also provide a comprehensive background on diagnosis and current therapeutic strategies as well as reviewing preclinical models of uLMS, which may be employed not only in testing emerging therapies but also in understanding this challenging and deadly disease.

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Section: Genomic Landscapementioning

confidence: 94%

Section: Treatmentmentioning

confidence: 99%

Interrogating the Genomic Landscape of Uterine Leiomyosarcoma: A Potential for Patient Benefit

Dall

Hamilton

Ratnayake

et al. 2022

Cancers

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show abstract

“…The third patient died from rapidly progressive disease postsurgical resection after receiving pembrolizumab for only 1.5 months. In another case report by Wang et al, 17 a patient with a MSI-H uterine leiomyosarcoma showed partial response to pembrolizumab after three cycles but ultimately had disease progression after seven cycles. Our case therefore adds to the existing published data of response of MSI-H/MMRd sarcoma to ICI, albeit showing an extremely favorable response.…”

Section: Discussionmentioning

confidence: 96%

Soft Tissue Leiomyosarcoma With Microsatellite Instability, High Tumor Mutational Burden, and Programmed Death Ligand-1 Expression Showing Pathologic Complete Response to Pembrolizumab: A Case Report

Tay

Yeong

Chen

et al. 2022

JCO Precision Oncology

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“…The dMMR/MSI-H and TMB-H may provide a potential mechanism for the successful management of the LMS. Though MMR deficiency occurs infrequently in LMS, it has been reported in some studies, and the MMR-deficient status points to some LMS patients as potentially sensitive to immunotherapy (25)(26)(27). However, in a clinical trial of pembrolizumab, one dMMR sarcoma patient enrolled still developed progressive disease (7).…”

Section: Discussionmentioning

confidence: 99%

Case Report: Complete Response to Antiangiogenesis and Immune Checkpoint Blockade in an Unresectable MMR-Deficient Leiomyosarcoma Harboring Biallelic Loss of PTEN

Guo

Tong

et al. 2022

Front. Oncol.

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BackgroundLeiomyosarcoma (LMS) is a malignant smooth muscle neoplasm, in which the efficacy of immune checkpoint blockade (ICB) is very limited. What is worse, loss of PTEN, known as a negative factor for ICB, frequently occurred in LMS. Seeking new strategies for LMS patients harboring loss of PTEN is important and challenging.Case PresentationA 42-year-old Chinese male was diagnosed as having unresectable LMS of the iliopsoas. After the failure of two prior chemotherapy regimens, whole-exome sequencing revealed that tumor tissue had high tumor mutation burden (689 Muts), high microsatellite instability, and some somatic mutations, including PTEN (copy number loss and p.N323fs), MSH6 (p.F1088fs), TP53 p.R273C, ASXL1 p.G645fs, ATR p.S1843P, and CDKN2A p.A118P. Then, antiangiogenic agent (pazopanib or anlotinib) plus pembrolizumab was administered from January 2 to August 6, 2018. However, pazopanib was stopped on June 18 due to the grade 2/3 adverse effect of hand–foot skin reaction, and anlotinib was administered. Considering that the tumor shrunk after immunotherapy, he underwent radical resection on September 6, 2018. The final pathological diagnosis confirmed pathologic complete response (CR). Until the latest follow-up (September 15, 2021), no progressive disease was observed and total disease-free survival has exceeded 36 months.ConclusionWe presented a patient with an unresectable mismatch repair (MMR)-deficient LMS harboring biallelic loss of PTEN who achieved CR from a combination strategy of antiangiogenesis plus pembrolizumab. Such a strategy might be a promising strategy to overcome the ICB resistance caused by the loss of PTEN. Such conclusions need to be further confirmed in further investigations.

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Use of pembrolizumab in MSI-high uterine leiomyosarcoma; a case report and review of the literature

Cited by 11 publications

References 10 publications

Interrogating the Genomic Landscape of Uterine Leiomyosarcoma: A Potential for Patient Benefit

Interrogating the Genomic Landscape of Uterine Leiomyosarcoma: A Potential for Patient Benefit

Soft Tissue Leiomyosarcoma With Microsatellite Instability, High Tumor Mutational Burden, and Programmed Death Ligand-1 Expression Showing Pathologic Complete Response to Pembrolizumab: A Case Report

Case Report: Complete Response to Antiangiogenesis and Immune Checkpoint Blockade in an Unresectable MMR-Deficient Leiomyosarcoma Harboring Biallelic Loss of PTEN

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