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Fungi have a reputation for appearing where humans don’t want them: on crops, in basements and cold storage rooms, and in the human body. Worse, fungi are getting better at resisting conventional defenses, meaning we need to either use even more fungicides—which would exacerbate the resistance problem—or innovate our tools.

Researchers have now developed a spray that can keep fungi at bay. The nontoxic solution forms an extremely hydrophobic surface coating that makes it harder for fungi to latch on to a surface and kills them if they do take root.

Boaz Pokroy, a materials scientist at Technion—Israel Institute of Technology, and his colleagues decided to leverage their previous work with antibacterial fatty acids to develop a novel “dual mode” agent that is very difficult for the fungi to become resistant to. First, stearic acid, with its inherent hydrophobicity, keeps fungi from sticking to the surface. This alone reduced the growth of gray mold, Botrytis cinerea, by more than 60% on filter paper.

Second, the addition of a shorter-chain fatty acid, such as caprylic acid, provides fungicidal power against any fungi that manage to anchor themselves. With the combined fatty acids, the researchers were able to achieve total inhibition of the mold.

Pokroy and his team explain that after spraying, stearic acid forms crystal nuclei, which caprylic acid adsorbs onto. As the spray’s solvent evaporates, stearic acid crystals assemble into clusters, thus producing a rough surface imbued with adsorbed liquid layers of caprylic acid, which is primed to kill fungi. The caprylic acid leached out of the coating after about a week, thereby diminishing the potency of the coating.

Pokroy points to ventilation ducts as a prime location to use the new spray. Air ducts often become breeding grounds for fungi due to their damp, dark, and cold interiors. These fungi release fungal spores into the air. In hospital settings, those spores raise the risk of infection for already vulnerable people. Since conventional fungicides are toxic to humans and the environment, stringent limits exist on the site, quantity, and duration of their use.

Jonathan C. Barnes, a chemistry professor at Washington University in St. Louis who wasn’t involved in the study, commended the work and found the technology “very scalable,” as the same fatty acids are common ingredients of food and cosmetics.

“The fact that the dual-purpose coating was successfully applied to both glass slides and cellulose filter substrates is an indication that the technology could be used on a variety of surfaces and thus in many different applications,” he says. One potential application he saw was spraying this coating on medical implants, where a quick burst release of the medium-chain fatty acids may prevent infections during surgery.

Patients with polycythemia vera (PV) require treatment to reduce hematocrit and maintain quality of life over a significant span of time living with the disease. In a recent in-person Community Case Forum event in Santa Monica, California, Mojtaba Akhtari, MD, professor of medicine at Loma Linda University, discussed the trials in high-risk disease that not only looked at response to treatment but showed promise in reducing thrombotic events that represent the greatest risk to patients’ survival. Trials that have been ongoing for several years are now producing longer-term data that provides guidance on how to manage treating patients with PV most effectively and what trends indicate worse outcomes.

This article is part 2 of a 2-part series from a Community Case Forum event.

Targeted Oncology: Could you describe the design of the MAJIC-PV study [ISRCTN61925716]in patients with higher-risk PV?

Mojtaba Akhtari, MD: The MAJIC-PV study was done in the United Kingdom; Claire N. Harrison, MD, of St. Thomas’ Hospital in South London, did the MAJIC-PV study for patients with PV with a 1:1 randomization of 190 patients: one group received ruxolitinib [Jakafi] and the other group received best available treatment. They looked for complete or partial response, and if they had complete or partial response, they continued ruxolitinib as long as they had a partial response for up to 5 years, and in the other arm they were allowed to change the treatment.

A complete remission was getting hematocrit below 45%, white blood cell [WBC] count below 10,000/μL, platelet count less than 400,000/μL, no phlebotomy, and normalization of spleen size. Looking at those given ruxolitinib, they did better [HR, 0.38; 95% CI, 0.24-0.61; P < .001].¹ Looking at the event-free survival [EFS], they did better [HR, 0.58; 95% CI, 0.35-0.94; P = .03]. The patients on ruxolitinib had fewer thrombotic events. This is the first time that an intervention has shown it reduces the risk of thrombosis.

What data support the long-term use of ropeginterferon alfa-2b (Besremi) in high-risk PV?

The PROUD-PV and CONTINUATION-PV studies [NCT01949805; NCT02218047] enrolled adult patients with PV who were [either] naive patients in need of cytoreductive [therapy] or some patients pretreated with hydroxyurea with a 1:1 randomization. One arm received ropeginterferon, the other one received hydroxyurea, and patients were able to continue through 12 months, and then for up to 3 to 5 years, they continued with either ropeginterferon or best available treatment.

For ropeginterferon alfa-2b, the rate of complete hematologic response and normal spleen size at 12 months was 21% [vs 28% in the control group].² The rate of complete hematologic response only at 12 months was 43% [vs 46%], and molecular response at 12 months was 34% [vs 42%].

Hydroxyurea is very like old-fashioned chemotherapy. Interferon is more like targeted treatment that works through the immune system. We are not treating patients with chronic myeloid leukemia with hydroxyurea anymore, unless you want to control severe leukocytosis…so I’m not sure why we should give hydroxyurea to patients with PV, but it’s good to have discussions. Patients can have adverse events, but it’s usually well tolerated; the discontinuation rate is low.

In the long term, in year 6 of treatment for ropeginterferon, 81.4% were keeping the hematocrit below 45%; in the control arm, it was 60%.³ EFS was better for ropeginterferon, so patients would have fewer complications if they were on ropeginterferon.

What did the REVEAL study (NCT02252159) show about disease outcomes of PV?

This is the largest prospective observational study of PV in the United States. More than 2500 patients were enrolled, and 2200 patients were eligible. A total of 142 thrombotic events were observed: 100 were venous thrombotic events and 42 were arterial traumatic events.⁴

If we look at what the [lower-risk] patients were given as treatment, 54.3% only had phlebotomy, 18.1% had hydroxyurea only, 15.7% had phlebotomy and hydroxyurea, 7% other, and 5% watchful waiting. I don’t think I have patients with PV on watchful waiting because they need phlebotomy or they need to be on aspirin.

Looking at cumulative incidence of thrombotic events for these patients, high-risk patients had more thrombotic events vs low-risk patients [5.2% vs 2.78%]. Heart attack and stroke were what killed these patients. They looked at blood values to see which patients could get more blood clots. Patients whose hematocrit was more than 45% had more trouble. Patients whose WBC count was more than 11,000/μL and patients whose platelet count was more than 400,000/μL did worse. This is another study showing that leukocytosis and thrombocytosis matter in patients with PV.

Looking at the thrombotic events in the high-risk patients, those with erythrocytosis or hematocrit of more than 45%, leukocytosis with WBC count more than 11,000/μL, or thrombocytosis with platelet count than 400,000/μL were associated with worse outcomes.

_{DISCLOSURES: Akhtari previously reported consulting or advisory roles with Abbvie, BMS, Incyte, Karyopharm Therapeutics, Pfizer, and Takeda; and speakers’ bureau with Incyte, Jazz Pharmaceuticals, and Novartis.}

_References:

_{1. Harrison CN, Nangalia J, Boucher R, et al. Ruxolitinib versus best available therapy for polycythemia vera intolerant or resistant to hydroxycarbamide in a randomized trial. J Clin Oncol. 2023;41(19):3534-3544. doi:10.1200/JCO.22.01935}

_{2. Gisslinger H, Klade C, Georgiev P, et al. Ropeginterferon alfa-2b versus standard therapy for polycythaemia vera (PROUD-PV and CONTINUATION-PV): a randomised, non-inferiority, phase 3 trial and its extension study. Lancet Haematol. 2020;7(3):e196-e208. doi:10.1016/S2352-3026(19)30236-4}

_{3. Gisslinger H, Klade C, Georgiev P, et al. Ropeginterferon alfa-2b achieves patient-specific treatment goals in polycythemia vera: final results from the PROUD-PV/CONTINUATION-PV studies. HemaSphere. 2022;6:97-98. doi:10.1097/01.hs9.0000843676.80508.b5}

_{4. Gerds AT, Mesa R, Burke JM, et al. Association between elevated white blood cell counts and thrombotic events in polycythemia vera: analysis from REVEAL. Blood. 2024;143(16):1646-1655. doi:10.1182/blood.2023020232}