News in brief: Antihistamines may enhance response to cancer immunotherapy; SCLC insights clear path to personalised medicine; 3 oncology drugs among most expensive for PBS

Thursday, 2 Dec 2021

Antihistamines may enhance response to cancer immunotherapy

Cancer patients on immunotherapy could see added efficacy and survival benefits with concurrent H1-antihistamines, a new study suggests.

The study of 2,864 cancer patients on immuno- or chemotherapy with or without antihistamines found that anti-PD-1/PD-L1-treated lung cancer and melanoma patients on antihistamines had significantly improved survival over those off antihistamines (P = 0.015 and 0.0065 respectively).

Breast cancer and colon cancer patients on immunotherapy also saw a survival benefit, though not statistically significant due to the relatively small number of antihistamine-users.

“Notably, H1-antihistamines had minimal effect on the survival of chemotherapy-treated patients, suggesting that H1-antihistamines may not target tumor cells directly,” the authors wrote in Cancer Cell.

Instead, the drugs likely affect macrophages, which can become dysfunctional when exposed to high levels of histamine and histamine receptor H1 (HRH1) in the tumour microenvironment.

“Mechanistically, HRH1-activated macrophages polarise toward an M2-like immunosuppressive phenotype with increased expression of the immune checkpoint VISTA, rendering T cells dysfunctional,” the authors wrote.

“Antihistamine treatment reverted macrophage immunosuppression, revitalised T cell cytotoxic function, and restored immunotherapy response”.

They noted that histamine-HRH1-related allergy “facilitated tumour growth and induced immunotherapy resistance in mice and humans” and that “cancer patients with low plasma histamine levels had a more than tripled objective response rate to anti-PD-1 treatment compared with patients with high plasma antihistamine”.

“Altogether, pre-existing allergy or high histamine levels in cancer patients can dampen immunotherapy responses and warrant prospectively exploring antihistamines as adjuvant agents for combinatorial immunotherapy,” they concluded.

SCLC insights clear path to personalised medicine

New insights on small cell lung cancer (SCLC) development could lead to personalised treatments and reduced mortality, Australian researchers say.

A study of SCLC progression in mice showed MYC overexpression gave mutant neuroendocrine, club and alveolar type II cells a proliferative advantage, inducing adenoma or carcinoma in situ that didn’t continue to invasive disease.

Combined with Trp53 and Rb1 deletion, however, the mutations exclusively led to SCLC formation in all cell types — with each cell of origin influencing disease latency, metastatic potential and the SCLC phenotype’s transcriptional profile.

The findings suggest SCLC “is a series of diseases rather than being a single form of cancer” that only derives from neuroendocrine cells, a statement from the Hudson Institute of Medical Research read.

Understanding the drivers of SCLC will allow researchers to develop new, targeted therapies that improve survival outcomes, study coauthor and Hudson Institute STAT Cancer Biology Research Group Head Dr Daniel Gough said in the statement.

The full study is available in Oncogene.

3 oncology drugs among most expensive for PBS

Three drugs with oncology indications are on the Top 10 PBS drugs list by cost to government released by NPS MedicineWise this week.

Pembrolizumab (Keytruda) which is PBS listed for the treatment of solid cancers and elapsed/refractory classical Hodgkin Lymphoma was the second most expensive drug on the national list. For the year July 2020 – June 2021 it had a cost of $431,701 ,955 for 49,694 prescriptions.

Nivolumab (Opdivo) , which is PBDS listed for the treatment of non-small cell lung cancer (NSCLC)  was ranked third in terms of cost to government with costs of $402,113,073 for 50,593 prescriptions in 2020/2021.

Lenalidomide (Revlimid), which is listed on the PBS for treatment of multiple myeloma, was ranked ninth most expensive, at a cost of $221,365,364, based on 40,554 prescriptions.

The most costly PBS listed drug to government was aflibercept for age related macular degeneration (AMD) with a cost of $443,729,600 per year.

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