Checkpoint inhibitor immunotherapy prior to surgery improved outcomes in brain cancer treatment
Pembrolizumab (Keytruda, Merck) treatment initiated prior to surgery and continued afterwards extended survival and induced better anti-tumor responses than post-surgery-only administration of the PD-1-blocking MAb in glioblastoma patients. In a small clinical trial involving 35 subjects with recurrent surgically resectable tumors, those who received pembrolizumab first lived on average 420 days compared to 230 days in those who received it after surgery.1
Neoadjuvant administration of pembrolizumab was associated with enhanced T-cell expansion and downregulation of cell cycle-related genes in the tumor.
“By administering the immunotherapy before surgery, we activated the T cells within the tumor that were previously functionally impaired, which is essentially what helped extend people’s lives,” lead author Timothy Cloughesy of University of California in Los Angeles said.
Glioblastoma is an aggressive form of cancer, which has so far shown little response to immunotherapeutic approaches. Patients with recurrent disease live the average of 6–9 months.
(1) Cloughesy TF, Mochizuki AY, Orpilla JR, Hugo W, Lee AH, Davidson TB, Wang AC, Ellingson BM, Rytlewski JA, Sanders CM, Kawaguchi ES, Du L, Li G, Yong WH, Gaffey SC, Cohen AL, Mellinghoff IK, Lee EQ, Reardon DA, O’Brien BJ, Butowski NA, Nghiemphu PL, Clarke JL, Arrillaga-Romany IC, Colman H, Kaley TJ, de Groot JF, Liau LM, Wen PY, Prins RM. Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma. Nat Med 2019; doi: 10.1038/s41591-018–0337-7
Seasonal influenza vaccine effectiveness reaches almost 50% in the US, interim results show
The seasonal influenza vaccine has prevented 47% cases of medically attended acute respiratory virus infection in the US, according to an interim report by the Centers for Disease Control and Prevention based on data collected from November through February.1 This represents an increase from last year’s 38%.
European countries report vaccine effectiveness ranging from 45% to 70%. The quadrivalent live attenuated nasal-spray vaccine has prevented 87% of influenza caused by the main circulating strain, H1N1, in UK children aged 2–17 years.2 The UK also noted an increased vaccination rates in this vulnerable population.
(1) Blanton L, Dugan VG, Abd Elal AI, Alabi N, Barnes J, Brammer L, Budd AP, Burns E, Cummings CN, Garg S, Garten R, Gubareva L, Kniss K, Kramer N, O’Halloran A, Reed C, Rolfes M, Sessions W, Taylor C, Xu X, Fry AM, Wentworth DE, Katz J, Jernigan D. Update: Influenza Activity – United States, September 30, 2018–February 2, 2019. MMWR Morb Mortal Wkly Rep 2019; 68:125–134
(2) Kissling E, Rose A, Emborg HD, Gherasim A, Pebody R, Pozo F, Trebbien R, Mazagatos C, Whitaker H, Valenciano M, European Ive Group. Interim 2018/19 influenza vaccine effectiveness: six European studies, October 2018 to January 2019. Euro Surveill 2019; 24(8)
PD-1 blockade immunotherapy successful as first-line therapy of aggressive form of skin cancer
56% of patients with recurrent, locally advanced or metastatic Merkel cell carcinoma reported long-lasting responses, 24% with complete remission, after receiving the PD-1 inhibitor MAb pembrolizumab in a Phase 2 trial enrolling 50 subjects.1 70% of the patients were alive after two years.
“This is the earliest trial of immunotherapy as a front-line therapy for Merkel cell carcinoma, and it was shown to be more effective than what would be expected from traditional therapies, like chemotherapy. Immunotherapy provides an effective treatment for patients with Merkel cell carcinoma who before had few options,” senior author Suzanne Topalian of Johns Hopkins University said.
Pembrolizumab was granted accelerated approval by the US Food and Drug Administration for advanced Merkel cell carcinoma in 2018.
(1) Nghiem P, Bhatia S, Lipson EJ, Sharfman WH, Kudchadkar RR, Brohl AS, Friedlander PA, Daud A, Kluger HM, Reddy SA, Boulmay BC, Riker AI, Burgess MA, Hanks BA, Olencki T, Margolin K, Lundgren LM, Soni A, Ramchurren N, Church C, Park SY, Shinohara MM, Salim B, Taube JM, Bird SR, Ibrahim N, Fling SP, Homet Moreno B, Sharon E, Cheever MA, Topalian SL. Durable Tumor Regression and Overall Survival in Patients With Advanced Merkel Cell Carcinoma Receiving Pembrolizumab as First-Line Therapy. J Clin Oncol 2019; doi: 10.1200/JCO.18.01896
A universal influenza vaccine candidate had promising phase 2 results
The universal influenza vaccine candidate M2SR (FluGen) protected against a mismatched strain in a placebo-controlled Phase 2 challenge study involving 100 healthy adults. The vaccine, which is an M2-deleted single replication H3N2 strain from the 2007 season, reduced viral load by 34% compared with placebo after participants had been challenged with the 2014 strain. M2SR also reduced symptoms of disease by 50%.
Combination immunotherapy helped some patients with metastatic prostate cancer
The CTLA-4 inhibitor ipilimumab (Yervoy) together with the PD-1 inhibitor nivolumab (Opdivo, both BMS) induced tumor shrinkage after ~1 year in a subset of patients with castration-resistant prostate cancer that progressed after prior therapy. Among 32 subjects who had been treated with hormonal therapy, 25% responded. There were 10% responders in 30 subjects who had undergone chemotherapy. Two patients from each cohort saw their tumors disappear completely. However, around half of subjects discontinued the trial due to disease progression.
“This was the first combination trial of two immune checkpoint therapies in prostate cancer. These results support the idea that immune checkpoint blockade can play an important role in the treatment of these patients and provide the foundation to test this strategy in a larger clinical trial,” principal investigator Padmanee Sharma of MD Anderson Cancer Center said.
Prostate cancer has proven difficult to treat with immune-targeting monotherapies in previous clinical trials due to low T-cell infiltration into the tumor microenvironment.
Vaccine against metapneumovirus and parainfluenza was immunogenic in a phase 1 trial
Single vaccination with mRNA-1653 (Moderna) was sufficient to elicit neutralizing antibodies against human metapneumovirus and parainfluenza type 3 according to interim data from a randomized, placebo-controlled, dose-escalation Phase 1 study. No serious adverse events were reported. The vaccine consists of two mRNAs encoding fusion proteins from the two viruses formulated in a lipid nanoparticle.
There are no licensed vaccines for these two infections, which cause severe respiratory diseases particularly in children.
Clinical trial starts for a therapeutic HPV vaccine regimen
66 women positive for HPV strains 16 and 18 are enrolled in a randomized, double-blind, placebo-controlled Phase 1/2 study of a combination of therapeutic vaccines. They will receive the adenovirus-based Ad26.HPV16 or Ad26.HPV18 (Janssen) as a prime followed by the Modified Vaccinia Ankara-vectored MVA.HPV16/18 as a boost (Bavarian Nordic). The main objective of the study is to evaluate safety, reactogenicity and immunogenicity of the regimen. While prophylactic HPV vaccines exist, there are no therapeutic vaccines for HPV-positive women to prevent tumorigenesis.
Two trials will test oral norovirus vaccine
The oral tablet vaccine VXA-G1.1-NN (Vaxart) will be tested in a Phase 2 challenge study. The adenovirus-vectored vaccine, which consists of noroviral GI.1 VP1 and a dsRNA adjuvant, was shown in a previous study to be safe and immunogenic. Another Phase 1 will test a bivalent vaccine from the same company. There is no licensed vaccine against norovirus, which is a common cause of gastroenteritis.
Egg allergy immunotherapy was effective for at least 5 years
Oral immunotherapy of egg allergy allowed a subset of patients to incorporate eggs into their diet ≥5 years after they had stopped the treatment. In a randomized, placebo-controlled trial 55 egg-allergic subjects received immunotherapy or placebo for four months, after which their sensitivity for eggs was tested. 50% did not have any reaction, and all of these subjects could eat eggs in any form for the following 5 years. The remaining group had a more variable reaction to both concentrated and baked egg.
“These results further support the effectiveness of [oral immunotherapy] as a safe way of desensitizing children and youth with egg allergy,” study leader Edwin Kim of University of North Carolina said. “Past research also suggests that eating egg may actually shorten the amount of time a patient has the allergy, so any amount of egg that is incorporated into an allergy patient’s diet is helpful.”
Pneumococcal vaccine candidate has entered human testing
Safety and immunogenicity of the pneumococcal vaccine ASP3772 (Astellas and Affinivax) will be evaluated in a Phase 1/2 trial, which enrolls >600 adults. In the first stage, the optimal dose will be determined in subjects aged <65 years. The second stage will focus on the vulnerable population of the elderly. ASP3772 will be compared with the licensed Prevnar 13 (Pfizer) and Pneumovax 23 (Merck).
ASP3772 is based on Multiple Antigen Presenting System, which allows the incorporation of more strains than in licensed conjugate or polysaccharide vaccines. It is designed to induce T-cell responses and reduce nasopharyngeal colonization.
High-fiber diet might improve immunotherapy of melanoma
Melanoma patients who ate high-fiber food were five times as likely to benefit from anti-PD-1 MAb immunotherapy compared to subjects on low-fiber diet, according to a study that investigated 46 patients. Eating whole grains, fruits, vegetables and other high-fiber diet was correlated with the presence of gut bacteria previously shown to improve immunotherapy outcomes. The researchers could show that high gut microbiota diversity was associated with better responses to any form of treatment.
“We know from prior research that eating a higher-fiber diet has a lot of health benefits,” said Christine Spencer of Parker Institute for Cancer Immunotherapy who presented the study at the AACR Annual Meeting. “But with this preliminary research on cancer patients and the microbiome, it appears that fiber is also linked to a better response to immunotherapy.”
In contrast, using probiotics was associated with lower diversity of gut microbiota in melanoma patients.