Patients with haematological cancers are at higher risk of COVID-19 infection and experience more severe disease compared to people with other cancers, say experts discussing the latest evidence on COVID-19.  

Speaking as part of an expert panel assembled for a COVID-19 webinar sponsored by Janssen-Cilag, Dr Benjamin Teh, an infectious diseases physician at the Peter MacCallum Cancer Centre in Melbourne, said the COVID-19 case fatality ratio in cancer patients – at between six and 11%¹ – was higher than the general population.

He noted that in a recently submitted paper in Lancet Oncology² the fatality ratio was considerably higher in haematology patients – at 33% followed by lung cancer at 18%.

“Not only do these patients see more rapid deterioration during their progression to severe disease at a median of 13 days versus 43¹ days in the general population, they will also experience a higher rate of concurrent infections – 19% vs 2.2%², have higher rates of ICU admission and rates of mechanical ventilation and, understandably, high rates of death,” Dr. Teh said.

While hypertension, cardiovascular disease, diabetes, smoking and high BMI were all associated with severe disease and poor outcomes in the general population, Dr. Teh pointed out that for cancer patients, particularly those with haematological malignancies, the worse the cancer control the higher the risk for ICU admission, ventilation, severe symptoms or death¹.

Cancer therapy or surgery within 40 days of presentation with COVID-19 symptoms was also associated with severe events – and the type of cancer treatment that had been delivered also counted towards more severe outcomes².

Clinical presentation in cancer patients 

Looking to data from two recent retrospective case studies of coronavirus disease in hospitals within Wuhan, China^{3, 4} infectious diseases specialist Dr. Orla Morrissey from Alfred Health in Melbourne said COVID-19 was much more prevalent among cancer patients – at a rate of 2.2% which was 1.7 times higher than the general population.

Cancer patients commonly experienced dry cough and acute fever while a lot of patients had lymphopenia – more than in the general population – which she said might reflect their underlying haematological condition.

“Studies have described a decrease in lymphocyte count and that may be something that our cancer patients may already have…maybe what we really need to look at is their previous lymphocyte counts and whether there has been a drop rather than just the lymphopenia itself,” Dr. Morrissey told webinar participants.

Other clinical features³ seen in cancer patients included dyspnoea, high levels of high-sensitivity C-reactive protein (CRP), anaemia and hypoproteinemia. Common chest CT findings included ground-glass opacification (75%) and patchy consolidation (46.3%).

According to Dr Morrissey screening for COVID-19, including CT scans and nucleic acid test, was the key to potentially reducing the risk of severe complications and mortality in cancer patients.

She advised that blood tests include a full blood count, a test for urea and electrolytes, liver function tests, CRP, blood glucose, INR, APTT, D-dimer, lactate dehydrogenase and lactate.

“These are really more to support your diagnosis rather than making it but they are also useful as markers of severity as well as help guide you in terms of how the patient is actually progressing – is the patient getting better or worse – and to determine what you need to do in terms of treatment,” she noted.

Potential treatments are a story that is still unfolding

According to Dr. Teh the early message was that there were currently no good treatments for COVID-19 and evidence had not been strong for those that have shown early promise, such as hydroxychloroquine.

Early randomised control trials^{5 6 7 8 9 10} showed that the antimalarial had no clinical benefit and there was no difference in viral clearance.

“When you look at very secondary outcomes or ad hoc analysis perhaps there might be an early resolution of cough and fever by one day and there was also reports of a resolution of CRP on imaging but no clear clinical benefit and of course there’s the limitations of observational studies,” he said.

Another treatment that appears to have fallen out of favour was lopinavir/ritonavir (LPV/r) Dr. Teh said.

“A randomised control trial¹¹ showed no additional benefit to standard of care …and it certainly comes with several limitations, in particular side-effects and drug-drug interactions especially for a haematology patient.”

He noted that a lot of interest had also been generated in the RNA polymerase inhibitor remdesivir.

“So far this is just an observational study published in the New England Journal of Medicine¹² of 53 patients who received treatment through compassionate access. Of the 53 patients 64% where on mechanical ventilation when they were receiving treatment and 68% of those patients improved their category of oxygen support.”

“The authors do report an overall 84% clinical improvement, which includes being alive at discharge but comes from patients who are on low flow oxygen or not even receiving oxygen when they were on remdesivir,” he added.

There was also lot of interest in using IL-6 inhibitors, particularly in severe disease, Dr Teh noted.

“So far, we have a case series that shows that perhaps there was a 75% reduction and a 91% improvement in pulmonary imaging which is quite subjective,” he said¹³.

Other areas of interest include the use of convalescent plasma, which Dr. Teh and his team are currently investigating.

So far, a small case series¹⁴ of five patients has been published but these patients were critically ill and had a high viral load despite having antiviral therapy and despite receiving methylprednisolone in the ICU.

“When they were given convalescent plasma they had an improvement in their SOFA score, there was a resolution of ARDS and 60% were able to be weaned from ventilation but again it’s a small case series so it’s hard to know what the true effect is.”

If you would like to view a recording of the event when it is available online, please notify Janssen here.

References

1. Wenhua Liang,Weijie Guan,Ruchong Chen et al. Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China. The Lancet Oncology Mar 2020 DOI:https://doi.org/10.1016/S1470-2045(20)30096-6
2. Hui Li, Liang Liu, Dingyu Zhang et al. SARS-CoV-2 and viral sepsis: observations and hypotheses. The Lancet. Published online April 17, 2020 https://doi.org/10.1016/S0140-6736(20)30920-X
3. Zhang L, Zhu F, Xie L, et al. Clinical characteristics of COVID-19-infected cancer patients: A retrospective case study in three hospitals within Wuhan, China. Annals of Oncology. doi:10.1016/j.annonc.2020.03.296
4. Wei-jie Guan, Ph.D., Zheng-yi Ni, M.D., Yu Hu, M.D et al. Clinical Characteristics of Coronavirus Disease 2019 in China. NEJM 2020 Feb DOI: 10.1056/NEJMoa2002032
5. Zhaowei Chen, Jijia Hu, Zongwei Zhang, et al. Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial medRxiv 2020.03.22.20040758; doi: https://doi.org/10.1101/2020.03.22.20040758
6. CHEN Jun(),LIU Danping,LIU Li, et al. A pilot study of hydroxychloroquine in treatment of patients with common coronavirus disease-19 (COVID-19). J Zhejiang Univ (Med Sci), 2020, 49(1): 0-0.URL:http://www.zjujournals.com/med/10.3785/j.issn.1008-9292.2020.03.03
7. Wei Tang, Zhujun Cao, Mingfeng Han, et al. Hydroxychloroquine in patients with COVID-19: an open-label, randomized, controlled trial. medRxiv 2020.04.10.20060558; doi: https://doi.org/10.1101/2020.04.10.20060558
8. Gautret et al. (2020) Hydroxychloroquine and azithromycin as a treatment of  COVID‐19: results of an open‐label nonrandomized clinical trial. International Journal of  Antimicrobial Agents – In Press 17 March 2020 – DOI : 10.1016/j.ijantimicag.2020.105949
9. Million et al. Hydroxychloroquine-Azithromycin and COVID-19. IHU Preprint 2020
10. Molina et al, Medecine Maladies Infectieuses 2020
11. Cao et al,A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19  New Engld J Med 2020 Mar
12. Grein et al, Compassionate Use of Remdesivir for Patients with Severe Covid-19.  New Engld J Med 2020 Apr
13. Xu XL, Han MF, Li TT, Sun W, Wang DS, Fu BQ, Zhou YG, Zheng XH, Yang Y, Li XY, Zhang XH, Pan AJ, Wei HM. Effective treatment of severe COVID-19 patients with tocilizumab. ChinaXiv. 2020;202003(00026):V1
14. Shen et al, Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. JAMA 2020 Mar doi:10.1001/jama.2020.4783