Hyperprogression and Immunotherapy: Fact, Fiction, or Alternative Fact?

Adashek, Jacob J.; Subbiah, Ishwaria Mohan; Matos, Ignacio; Garralda, Elena; Menta, Arjun K.; Ganeshan, Dhakshina Moorthy; Subbiah, Vivek

doi:10.1016/j.trecan.2020.01.005

Cited by 95 publications

(92 citation statements)

References 25 publications

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“…Moreover, besides a complete/partial response, stable disease, and progressive disease, one should be aware of two additional patterns of tumor response when using immunotherapy, namely: pseudoprogression (i.e., apparent increase in the tumor burden initially, followed by delayed tumor shrinkage, which could lead to the premature cessation of effective immunotherapy) [ 20 , 21 ] and hyperprogressive disease (i.e., accelerated tumor progression following the introduction of ICIs) [ 22 , 23 ]. Hyperprogressive disease was shown to be associated with older age—in a study including 131 patients treated with anti-PD-1/PD-L1 therapy, 7 out of 36 patients ≥65 years old (19%) were classified as having hyperprogressive disease, compared with 5 out of the 95 patients ≤64 years old (5%), p = 0.01, of which only one patient was <55 years old [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

Immunotherapy in Corticotroph and Lactotroph Aggressive Tumors and Carcinomas: Two Case Reports and a Review of the Literature

Ilie

Salle

et al. 2020

JPM

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Once temozolomide has failed, no other treatment is recommended for pituitary carcinomas and aggressive pituitary tumors. Recently, the use of immune checkpoint inhibitors (ICIs) has raised hope, but so far, only one corticotroph carcinoma and one aggressive corticotroph tumor treated with immunotherapies have been reported in the literature. Here, we present two cases, one corticotroph carcinoma and one aggressive prolactinoma (the first one reported in the literature) treated with ipilimumab (1 mg/kg) and nivolumab (3 mg/kg) every three weeks, followed by maintenance treatment with nivolumab (3 mg/kg every 2 weeks) in the case of the corticotroph carcinoma, and we compare them with the two previously reported cases. Patient #1 presented a biochemical partial response (plasma ACTH decreased from 13,813 to 841 pg/mL) and dissociated radiological response to the combined ipilimumab and nivolumab—the pituitary mass decreased from 37 × 32 × 41 to 29 × 23 × 42 mm, and the pre-existing liver metastases decreased in size (the largest one from 45 to 14 mm) or disappeared, while a new 11-mm liver metastasis appeared. The maintenance nivolumab (21 cycles) resulted in a stable disease for the initial liver metastases, and in progressive disease for the newly appeared metastasis (effectively treated with radiofrequency ablation) and the pituitary mass. Patient #2 presented radiological and biochemical progressive disease after two cycles of ICIs—the pituitary mass increased from 38 × 42 × 26 to 53 × 57 × 44 mm, and the prolactin levels increased from 4410 to 9840 ng/mL. In conclusion, ICIs represent a promising therapeutic option for aggressive pituitary tumors and carcinomas. The identification of subgroups of responders will be key.

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Section: Discussionmentioning

confidence: 99%

Immunotherapy in Corticotroph and Lactotroph Aggressive Tumors and Carcinomas: Two Case Reports and a Review of the Literature

Ilie

Salle

et al. 2020

JPM

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“…Our results suggest for the first time, to our knowledge, that some patients who do not respond early to platinum-based chemotherapy are at higher risk for the development of HPD upon immunotherapy. ICIs may promote tumor growth kinetics in certain patients and lead to the development of HPD, with an incidence ranging from 4 to 29% in different studies [21,28] There is no uniform definition for HPD, even though some authors still doubt its existence because it is an ad-hoc observation, and may reflect the natural history of disease [29,30]. The majority of researchers rely upon the rate of target lesion growth to define HPD [21,31,32].…”

Section: Discussionmentioning

confidence: 99%

Sarcopenia and high NLR are associated with the development of hyperprogressive disease after second-line pembrolizumab in patients with non-small-cell lung cancer

Petrova¹,

Donev²,

Radanova

et al. 2020

Clinical and Experimental Immunology

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The aim of this multi-center retrospective study was to evaluate the incidence of hyperprogressive disease (HPD) after second-line treatment with pembrolizumab in patients (n = 167) with metastatic non-small-cell lung cancer (NSCLC) whose tumors expressed programmed cell death ligand 1 (PD-L1) in ≥ 1% and to search for hematological and imaging biomarkers associated with its development. Prior to chemotherapy, neutrophil : lymphocyte ratio (NLR1) and platelet : lymphocyte ratio (PLR1), and prior to immunotherapy, NLR2 and PLR2 were retrospectively analyzed. The psoas major muscle area (PMMA) was calculated at the L3 position on computed tomography before chemotherapy (PMMA1) and before immunotherapy (PMMA2) (n = 112). Patients with ∆PMMA (1-PMMA2/ PMMA1) × 100 ≥ 10% were considered to have sarcopenia (low muscle mass). After treatment with pembrolizumab on the first computerized tomography (CT) scan evaluation, patients were subdivided as follows as: hyperprogressors (HPs), progressors (Ps), non-progressors (NPs) and pseudoprogressors (PPs). HPs had significantly higher ∆PMMA levels, NLR2 and PLR2 than the other patients. Moreover, in multinomial logistic regression analysis, higher levels of ∆PMMA were associated with a decreased likelihood of being a P [odds ratio (OR) = 0•81; 95% confidence interval (CI) = 0•65-0•99; P = 0•047] or an NP (OR = 0•76; 95% CI = 0•62-0•94; P = 0•012) versus an HP. Higher NLRs tended to decrease the likelihood of being a P versus an HP (OR = 0•66; 95% CI = 0•42-1•06; P = 0•09) and significantly decreased the likelihood of being an NP versus an HP (OR = 0•44; 95% CI = 0•28-0•69; P < 0•0001). Our data suggest that a high pre-immunotherapy NLR2 and the presence of sarcopenia are potential risk factors for the development of HPD.

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“…PTEN alterations have also been associated with lower ORR and shorter progression‐free survival (PFS) independently of clinical factors and PD‐L1 status in triple‐negative breast cancer (TNBC) patients treated with ICPI 19 . In addition, studies have indicated that the MDM2 proto‐oncogene, a negative regulator of the TP53 gene, when amplified as seen in multiple tumors, may be associated with disease hyperprogression in patients treated with PD‐1/PD‐L1 inhibitors 20 …”

Section: Introductionmentioning

confidence: 99%

Predictive Biomarkers for Immune Checkpoint Inhibitors in Metastatic Breast Cancer

Sivapiragasam

Kumar

Sokol³

et al. 2020

Cancer Medicine

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Hyperprogression and Immunotherapy: Fact, Fiction, or Alternative Fact?

Abstract: The phenomenon of hyperprogressive disease (HPD) is a provocative phenomenon in the era of immune checkpoint inhibitors (ICI). Multiple groups report HPD in a variety of cancers treated with ICI and it to be associated with shorter progression free survival and overall survival.

Cited by 95 publications

References 25 publications

Immunotherapy in Corticotroph and Lactotroph Aggressive Tumors and Carcinomas: Two Case Reports and a Review of the Literature

Immunotherapy in Corticotroph and Lactotroph Aggressive Tumors and Carcinomas: Two Case Reports and a Review of the Literature

Sarcopenia and high NLR are associated with the development of hyperprogressive disease after second-line pembrolizumab in patients with non-small-cell lung cancer

Predictive Biomarkers for Immune Checkpoint Inhibitors in Metastatic Breast Cancer

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