COVID-19 Presents an Opportunity for Precision Medicine to Play Expanded Role in Care

Kashyap Patel, MD, BCMAS

Kashyap Patel, MD, BCMAS

The world is facing the unprecedented crisis of a novel coronavirus, also known as COVID-19. This virus was previously referred to as novel betacoronavirus- Severe Acute Respiratory Syndrome Virus- coronavirus 2 (SARS-CoV-2).¹What started in early December 2019 with 3 patients diagnosed with unexplained pneumonia in the Wuhan province in China has led to a global pandemic. At the time of writing this article, a total of 378,392 cases have been reported and 16,490 patients have died across 192 countries.²The US alone has reported 43,449 new cases and mortality of 545 patients.³

The World Health Organization (WHO) has declared COVID-19, caused by SARS-CoV-2, a public health emergency of international magnitude and a global pandemic in March 2020.⁴The definition of a pandemic according to the WHO is a worldwide spread of a new disease for which most people do not have immunity. A pandemic occurs when a new disease emerges and spreads around the world, and most people do not have immunity.

A sudden surge in the cases of COVID-19 due to pandemic, along with efforts to contain it, has led to multiple challenges that no country has experienced in the last several decades. The global pandemic from COVID-19 poses a unique set of challenges not only for patients with cancer who need their treatment, but also for caregivers, oncologists, and the overall care team. Although it is recognized that there is a need to treat cancer patients during a pandemic, due to their immunocompromised state from the nature of their disease or type of treatment they are receiving, it is of paramount importance that the oncology care team develop and evolve a systemic approach that prioritizes patients, disease, and types of treatment. In many instances, cancer is a potentially life-threatening disease when left untreated. A system to determine a priority for treatment of patients with cancer is necessary to have a consistent approach for all providers. So far, the efforts of organizations and individual oncologists are being outpaced rapidly by the exponential and logarithmic growth of patients with COVID-19. It is likely that this will be a dynamic situation that will vary from day-to-day.

Deaths from COVID-19 have been caused by multiple organ dysfunction. This observation might be attributable to the widespread distribution of angiotensin converting enzyme 2—the functional receptor for SARS-CoV-2— in multiple organs.^5,6Patients with cancer are more susceptible to infection than individuals without cancer because of their malignancy and anticancer treatments, such as chemotherapy.⁷These patients might be at increased risk of COVID-19 and have a poorer prognosis.

Rapid growth in the number of patients with symptoms from COVID-19 has led to capacity pressures to the healthcare system on a local, regional, and national level. This impact on delivery of care is compounded by mandates from government authorities such as local shelter-in-place orders, as well as school closures, and quarantines. Cancer clinics and hospital inpatient and outpatient areas have started experiencing capacity challenges. Patients with cancer are faced with difficult decisions and anxieties related to the risks of treatment versus exposure and increased risk of contracting COVID-19 infection. Theoretically, it is possible that the COVID-19 global pandemic will hit in one or more waves. Each wave likely may last for several weeks. At the peak of the COVID-19 wave, a significant portion of staff will be ill or not be available to work (eg, due to school closures, family obligations, fear, disease, illness, etc).

The COVID-19 pandemic represents an unprecedented time in medicine, particularly for patients with cancer. Both patients and their oncology care teams are facing a predicament about the right balance between use of immunosuppressive treatment and risk of cancer progression. In the only study published by Wenhua Liang, PhD, and colleagues analyzed the risk for severe COVID-19 in patients with cancer.⁸They reported that patients with cancer might have a higher risk of COVID-19 than individuals without cancer. They emphasized that patients with malignancy had poorer outcomes from COVID-19, providing a timely reminder to physicians that more intensive attention should be paid to patients with cancer to prioritize treatment versus risk of death and adverse outcomes. Patients who underwent chemotherapy or surgery in the past month had a numerically higher risk (three of four [75%] patients) of clinically severe events than did those not receiving chemotherapy or surgery, observed by logistic regression (odds ratio [OR] 5.34, 95% CI,1.80—16.18;P=.0026) after adjusting for other risk factors, including age, smoking history, and other comorbidities.

The authors have proposed 3 major strategies for patients with cancer in the COVID-19 crisis. First, an intentional postponing of adjuvant chemotherapy or elective surgery for stable cancer in endemic areas. Second, stronger personal protection provisions should be made for patients with cancer or cancer survivors. Third, more intensive surveillance or treatment should be considered when patients with cancer are infected with COVID-19, especially in older patients or those with other comorbidities.

Oncologists and institutions treating these patients face the continued challenges of treating patients while simultaneously reducing the risk of complications in the event they end up contracting COVID-19. For patients in complete remission on maintenance therapy, stopping chemotherapy may be an option. In those patients, we may be able to switch chemotherapy from IV to oral therapies. This would decrease the frequency of clinic visits. A chemotherapy break may be an option when feasible. Delays or modifying adjuvant treatment may be balanced with the risk of recurrence. It goes without saying that the prophylactic growth factors and antibiotics in high-risk chemotherapy regimens is of paramount importance. In cases where the absolute benefit of adjuvant chemotherapy may be quite small, and where non-immunosuppressive options are available (eg, hormonal therapy in estrogen receptor positive early-stage breast cancer), risk of infection with COVID-19 may be considered as an additional factor in weighing the different treatment options available to the patient.

The Role of Precision Medicine

Providers caring for cancer patients undergoing cytotoxic chemotherapy need to consider changing their treatment when feasible to reduce the risk of life-threatening complications as well as reducing the frequency of their visits to clinics. Targeted therapies are approved for a number of aggressive cancers from non—small cell lung cancer, stage IV melanoma, to acute myeloid and lymphoid leukemia. These therapeutic options offer an opportunity to consider treatment of patients with the likelihood of a better response while at the same time increasing dose density and intensity without raising the toxicity profile.

Precision medicine guided targeted therapies as well as immunotherapy may have a special role in identifying appropriate patients who may be in need for cancer treatment. Most targeted agents are orally administered agents. The toxicity and side effects profiles of many orally administered targeted therapies is significantly different from chemotherapy. A much higher complication rate from cytotoxic chemotherapy places patients with cancer at a much higher risk of complications from COVID-19 infection. Rigorous biomarker testing and appropriate therapeutic choice should be considered in this patient population, especially in the face of a global pandemic.

Cancer Patients Assessment and Treatment Priority Determination (top, intermediate and low priority)

Instead of an arbitrary approach, a system to determine the priority for consultation and treatment of patients with cancer may provide a consistent approach for all patients and providers. It is also important to avoid, as much as possible, having different levels of care. We recommend following a “cancer patient assessment and treatment priority determination” that would assist cancer clinics and decision makers in the management of patients with cancer. Given the dynamic situation, it is likely that this will vary from day-to-day, and daily accommodation re-assessment may be required. The patient priority assessment and classification would allow flexibility determined by the local circumstances and available resources. The local or regional circumstances and the availability of resources may influence a cancer clinics’ ability to follow the criteria.

Treatment priority category

Description

Examples of treatment with precision medicine guided targeted agents

Top Priority

Patients with newly diagnosed aggressive tumors such as DLBCL, ALL, AML, small cell lung cancer, brain metastases with swelling; pancytopenia, stage IV non—small cell lung cancer; stage IV melanoma; metabolic crisis; cord compression from prostate cancer related bone metastases; myeloma with skeletal events, hypercalcemia

Immunotherapy, targeted agents as well as oral agents (such as BTK inhibitors, venetoclax (Venclexta), anti-EGFR, TKIs, PARP inhibitors, FLT3 inhibitors, BRAF inhibitor

Intermediate Priority

Most patients requiring ongoing out-patient chemotherapy will be priority B. For patients starting therapy, recognizing that there are little to no data supporting long delays, this will be a judgement call for each patient.

For those patients who can be switched over to oral agents (consider less immunosuppressive agents in place of cytotoxic chemotherapy).

Maintenance regimen for lymphoma; convert patients on oral therapies if possible (BTK, targeted therapies, TKIs), PARP inhibitors for ovarian cancer, CDK4/6 for breast cancer

Convert patients (when feasible) on all oral regimen for prostate cancer, MM, high grade MDS, CLL, and MCL.

Low Priority

Patients receiving oral hormone therapy, especially in the adjuvant setting, HMA for low grade and risk MDS, growth factors for low grade MDS; adjuvant hormone blockers for prostate cancer; patients receiving bisphosphonates only. Patients on maintenance treatment with deep remission; these patients can be either followed using telehealth or rescheduled for less frequent follow up.

Low grade MDS

Low grade lymphoma

Smoldering multiple myeloma

Stage B colon cancer

Early stage breast cancer (low score Oncotype Dx)

MGUS

ALL indicates acute lymphoblastic leukemia; AML, acute myeloid leukemia; BTK, Bruton tyrosine kinase; CDK, cyclin-dependent kinase; CLL, chronic lymphocytic leukemia, DLBCL, diffuse large B-cell lymphoma; EGFR, epidermal growth factor receptor; MCL, mantle cell lymphoma; MDS, myelodysplastic syndrome; MGUS, monoclonal gammopathy of undetermined significance; MM, multiple myeloma; PARP, poly (ADP-ribose) polymerase; and TKI, tyrosine kinase inhibitor.

References

1. Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study.Lancet.2020; published online Jan 29. https://bit.ly/2JlMnsc. Accessed Marsh 27, 2020.
2. World Health Organization. Coronavirus disease (COVID-19) Pandemic. Coronavirus disease (COVID-19) outbreak situation. Updated March 24, 2020. https://bit.ly/33J1zJ2. Accessed March 24, 2020.
3. Coronavirus Disease 2019 (COVID-19). Cases in U.S. Updated March 24, 2020. https://bit.ly/2vKBtc6. Accessed March 24, 2020.
4. World Health Organization. WHO Director-General's opening remarks at the media briefing on COVID-19 - 11 March 2020. March 11, 2020. https://bit.ly/3al0yJE. Accessed March 24, 2020.
5. Zhou P, Yang XL, Wang XG, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin.Nature. 2020;579(7798):270—273. doi:10.1038/s41586-020-2012-7.
6. Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis.J Pathol. 2004;203(2):631—637. doi:10.1002/path.1570.
7. Kamboj M, Sepkowitz KA. Nosocomial infections in patients with cancer.Lancet Oncol. 2009;10(6):589—597. doi:10.1016/S1470-2045(09)70069-5.
8. Liang W, Guan W, Chen R, et al. Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China.Lancet Oncol. 2020;21(3):335—337. doi:10.1016/S1470-2045(20)30096-6.