Blood Cancer Uncensored was privileged to be a part of project to outline the impact of the pandemic on people with blood cancer and other immune compromise and to make recommendations. This was a truly international project with a broad range of stakeholders as can be seen by the list of signatories. A PDF version is also available and more information is available here.

Date of release: 21 February 2022

M

A multi-stakeholder coalition consisting of representatives from the global patient advocacy and clinical community has formed the International COVID-19 Blood Cancer Coalition (ICBCC) to address the specific impact of the pandemic on immunocompromised blood cancer patients (both acute and chronic), like those living with Chronic Lymphocytic Leukemia (CLL), and to recommend solutions and actions to mitigate those risks.

The Problem

The estimated share of those who are immunocompromised or immunosuppressed (IC/IS) is between two and three percent of the total global population. All are more vulnerable to contracting and suffering poor outcomes with COVID-19. Sadly, during the last two years their circumstances have been neglected to a larger or smaller extent with marked differences across geographical locations, leaving some to call them the “Prisoners of the Pandemic”.

Their antibody responses to COVID-19 vaccines and even boosters have been repeatedly proven to be less predictable and robust when compared to the general populationi,ii,iii. However, there is also evidence that boosters do yield benefits for people living with hematologic malignanciesxiii.

What we do know is that immunocompromised / immunosuppressed (IC/IS) patients1 in general, and blood cancer patients in particular, have:

1. Much greater risk from COVID-19 including higher rates of hospitalization, ICU admissions and deathiv.
2. Higher rates of breakthrough infections after being fully vaccinatedv.
3. Higher rates of their infection spreading to household contacts.
4. No simple lab test to reliably predict protection post vaccination.
5. Shown in some cases to carry and shed severe acute respiratory syndrome coronavirus 2 (orSARS-CoV-2) for months leading to the risk of introducing potentially dangerous new mutations into the broader populationvi.

While ∼97% of the adult population has the option of a safe and extremely effective way to prevent severe COVID-19 and can re-engage in the world by getting vaccinated, the vulnerable 2-3%, namely the IC/IS patients, continue to be cautioned by local and global health authorities not to rely on vaccines for protectionvii.

1 For the purposes of this statement, we use this definition of immunocompromised: Having a weakened immune system can make you more likely to get severely ill from COVID-19. Many conditions and treatments can cause a person to be immunocompromised or have a weakened immune system. Primary immunodeficiency is caused by genetic defects that can be inherited.  Also, the definition of who is considered immunocompromised is unclear and absent of precise diagnostic and clinical indicators. One example is those with Chronic Lymphocytic Leukemia (CLL) who have long been recognized as being significantly immunocompromised at all stages of disease, regardless of their treatment statusviii. Quoting from a recent study of COVID-19 vaccine response in blood cancer patients: “More than one-third (36%) of patients with CLL, the most common leukemia in U.S. adults, were seronegative after vaccination. Nearly three in ten of them had no cancer therapy in the past two years, showing that the disease itself may impair the B cell function needed to make antibodies to vaccines.” ix Moreover, we know that we can’t rely on any single blood test to determine vulnerability to COVID-19.

As a significant stressor, the COVID-19 pandemic has also resulted in the deterioration of mental health in some patient groupsx,xv, specifically multiple stressing factors of being immunocompromised, being less protected than others, and continuation of shielding from the environment, despite the relaxation of public rules.

Principles

The mantra of “Get vaccinated but act as if you are not” is an appropriate interim solution. But we cannot expect IC/IS patients to remain locked down indefinitely as the rest of the world returns to near normal.

The special vulnerability of those with blood cancers and others needs to be addressed in a proactive way. While we need to be prepared for surprises when dealing with COVID-19, certain principles can inform best practices for the IC/IS community:

1. We recognize that there is public fatigue with health measures.
2. Public awareness of issues for IC/IS is important.
3. IC/IS blood cancer patients must be included in the priority treatment groups with thoseconsidered at high risk and most vulnerable to COVID-19 infection. Everyone, regardless of their immune status, should be vaccinated. The active immunity from a vaccine is preferred for those who can rely on it. The more people are vaccinated, including booster vaccine doses, the more the IC/IS are protected.
4. Strategies and actions for IC/IS need to rely on antivirals and COVID-19 monoclonal antibodies (CmAbs).
5. Educating the IC/IS patients that continued masking and social distancing in high-risk circumstances are essential even if the public rules on masking and social distancing are relaxed. This is especially true in settings where the IC/IS will likely be present such as during public transit and in public buildings.
6. Safety measures and masking should continue to be maintained in any clinical setting when treating IC/IS patients even when public rules are being relaxed.

Recommendations

1. Access to fast response COVID-19 testing for high-risk patientsxvi. Many of the lifesaving therapies must be instituted quickly after diagnosis to be effective. Waiting a week for the results of a PCR test could be a fatal delay. Possible solutions include:
   1. Special access to home tests for the IC/IS community.
   2. Testing slots set aside or special testing sites for the IC/IS.
   3. Systems should be in place at national level to process the IC/IS that test positive toCOVID-19 to ensure a quick access to treatment.
2. Access to Pre-Exposure Prophylaxis or PrEP and Post Exposure Prophylaxis or PEP, and antivirals for high-risk patients. When vaccination doesn’t provide protection, there must be adequate access to appropriate therapies to prevent and treat infections. A critical claim, it can be achieved by accelerating the production and equitable distribution of antivirals and CmAbs. We have good options but scarce supplies.

3. Using scientific rigor to best define who is at high risk for COVID-19. It cannot be based on a single blood value and instead should be informed by the increasing volume of scientific literature on COVID-19 outcomes in several different IC/IS communities. This is especially true for all those with lymphoid malignancies including many lymphomas such as CLL/SLL (chronic lymphocytic leukemia/small lymphocytic lymphoma), regardless of whether they are before, during or after treatment.
4. More research is needed about blood cancer and IC/IS patients and existing and future antivirals.
5. Ensuring equitable access to best practices and treatments as well as affordable PPE and COVID-19 tests regardless of geographic, socio-economic, racial or ethnic considerations.
6. All those who might benefit should be offered additional or “booster” vaccine dosesxii. Booster vaccine doses should be offered especially to the elderly and immunocompromised based on studies demonstrating their protective benefits
7. Involvement of the medical institutions in low- and middle-income countries into the clinical studies / trials of new anti-COVID-19 medications.
8. Provision of psychological and psycho-oncological services specifically to the immunocompromised who need to continue shielding and social distancing despite the relaxation of public rulesxiv. Offering the right protective measures complete with a comprehensive strategy to protect the patients from the multiple stressing factors of being immunocompromised, less protected than others, being in lockdown or otherwise shielding from the environment will lead to better physical and mental health outcomes.
9. Vaccines must be made available globally, not only in high income countries. Reliable information about vaccines and treatments should be made available and more visible.

Until there is enough antiviral and antibody therapy for all who might benefit, difficult choices will need to be made to ensure equitable access.

Protecting the most vulnerable is not only the right thing to do, but also the smart thing to do. Protecting the immunocompromised where the virus has proven to linger and mutate, protects everyonexii.

COVID-19 management is changing rapidly. While this represents the consensus as to best practices at the time of its publication, new options will require ongoing updates. And so, it is also essential to ramp up research into identifying the factors of neglected care for the broader patient community of IC/IS patients.

Thank you for considering the needs of this large population that has been largely forgotten during the pandemic.

On behalf of the International COVID-19 Blood Cancer Coalition (ICBCC) 21st of February 2022

Endorsed by:

Global Patient Organisations:

Nick York, Chair

CLL Advocates Network (Global)

Dennis Costello, Executive Director
CML Advocates Network (Global)

Chris Tanti, CEO

Leukaemia Foundation (Australia)

Elke Stienissen, President

Lymphoma Association Flanders (Belgium)

Dr Brian Koffman, Executive Vice President and Chief Medical Officer
CLL Society
(USA)

Zack Pemberton-Whiteley, Chair

Acute Leukemia Advocates Network, ALAN (Global)

Sharon Winton, CEO

Lymphoma Australia (Australia)

Reymond Vles, Chair

CLL Canada (Canada)

Lorna Warwick, Chief Executive Officer Lymphoma Coalition (Global)

Fernando Piotrowski, Executive Director
Asociación ALMA (Argentina)

Hyacinth Grimes, Vice President

Lymphoma and Leukemia Foundation of Barbados (Barbados)

Nadine Prévost, Senior Director

The Leukemia & Lymphoma Society of Canada (Canada)

Silvia Diaz, President

AGALEMO (Costa Rica)

Rita O. Christensen, President
Patient Advocacy Group for Lymphoma, Leukemia and MDS, LyLe
(Denmark)

Jan Geissler, Chairman

Leukaemie Online (Germany)

Dražen Vincek, President

Hrvatska Udruga Leukemija i Limfomi, HULL (Croatia)

Pierre Aumont, Trustee

Ensemble Leucémie Lymphomes Espoir – ELLyE
(France)

Kimon Ourountzoglou

Hellenic Group of Patients with CLL (Greece)

Giora Sharf, Director

Flute of Light – Home of blood cancer patients in Israel (Israel)

Jana Pelouchova, President

Diagnóza Leukemie (Czech Republic)

Rainer Göbel, Chairman

Deutsche Leukämie- und Lymphom-Hilfe, DLH (Germany)

Vandana Gupta, Founder

V Care Foundation (India)

Lidija Pecova, President

HEMA (Macedonia)

Michael Rynne, Co-founder

CLL Ireland (Ireland)

Bahija Gouimi, President

AMAL (Morocco)

Emma Barker, Head of Support Services & Operations Leukaemia & Blood Cancer New Zealand

(New Zealand)

Maja Kocic, President

Lymphoma Patient Association LYPA / LIPA
(Serbia)

Dr Jeroen Goede, President

SFK- Stiftung zur Förderung der Knochenmarktransplantion (Switzerland)

Krishna Prasad Upadhyaya, Vice Chairman
Blood Cancer Society Nepal (Nepal)

Dr Gillian Corbett, Trustee

CLL Advocates New Zealand, CLLANZ
(New Zealand)

Elena Palma, International Representative AELCLES (Spanish Network for Leukemia and Blood Disorder) (Spain)

Rosmarie Pfau, President

Lymphome.ch Patientennetz Schweiz (Switzerland)

Marianne van Maarschalkerweerd, Expert Patient Advocate Hematon
(The Netherlands)

Oksana Chirun, President

Inter-regional public organization for patients with hematological diseases «Most Miloserdiya» («Mercy Bridge») (Russia)

Lise-lott Eriksson, President

Blodcancerförbundet / The Swedish Blood Cancer Association (Sweden)

Gerard Masalago, Chairman

Blood Cancer Foundation Tanzania (Tanzania)

Zack Pemberton-Whiteley, Chief Executive Officer Leukaemia Care
(UK)

Marc Auckland, Chair

CLL Support (UK)

Dr Adrian Warnock, Founder

Blood Cancer Uncensored (UK / USA / Canada)

Dallas Pounds, Director of Services Lymphoma Action (UK)

Helen Rowntree, Director of Research, Services & Engagement
Blood Cancer UK
(UK)

Ivan Zelenskyi, Director

Charity Fund of patients “Drop of Blood”
(Ukraine)

Jonathan Neil Mendelsohn, Trustee
Follicular Lymphoma Foundation (UK)

Tom Mallon, Coordinator

Leukaemia & Lymphoma NI (UK)

Gwen Nichols, MD, Chief Medical Officer
The Leukemia & Lymphoma Society
(USA)

Clinical community / Medical Societies:

Prof Paolo Ghia, President

European Research Initiative on CLL, ERIC
(Europe)

Prof Peter Hillmen, Chairperson

International Workshop on Chronic Lymphocytic Leukemia (iwCLL) (Global)

Dr Yervand Hakobyan, President

AHA – Armenian Hematology Association (Armenia)

Vanessa O’Shaughnessy,

Director Communications

Peter MacCallum Cancer Centre (Australia)

Dr. Kostas Stamatopoulos, Director
Institute of Applied Biosciences CERTH – Center for Research and Technology Hellas (Greece)

Dr Renata Walewska, Chair

UK CLL Forum (UK)

Nicole Lamanna, MD

Director CLL Program Hematologic Malignancies Section Herbert Irving Comprehensive Cancer Center
New York-Presbyterian/Columbia University Medical Center (USA)

Dr Versha Banerji, Physician

(Canada)

Dr Tamar Tadmor, Physician

The Israeli CLL Study Group (Israel)

Prof Paul Moss, Physician

Chief Investigator of the CLL- Vaccine Response Study, Birmingham
(UK)

Prof. Alain Delmer & Prof. Pierre Feugier
CLL Scientific Board French Innovative Leukemia Organization
(France)

Dr Vasile Musteata, Physician

State University of Medicine and Pharmacy “N. Testemitanu”, Institute of Oncology (Moldavia)

Anne Crook, Counsellor / Psychotherapist, Psycho- oncology
(UK)

8 | Page

Selected References:

1. Herishanu, Y., Avivi, I., Aharon, A., Shefer, G., Levi, S., Bronstein, Y., … Ghia, P. (2021). Efficacy of the BNT162b2 mRNA COVID-19 vaccine in patients with chronic lymphocytic leukemia. Blood, 137(23), 3165–3173. https://doi.org/10.1182/blood.2021011568.
2. Greenberger, L. M., Saltzman, L. A., Senefeld, J. W., Johnson, P. W., DeGennaro, L. J., & Nichols, G. L. (2021). Antibody response to SARS-CoV-2 vaccines in patients with hematologic malignancies. Cancer Cell, 39(8), 1031–1033. https://doi.org/10.1016/j.ccell.2021.07.012.
3. Re, D., Seitz-Polski, B., Carles, M., Brglez, V., Graça, D., Benzaken, S., … Jérôme, B. (2021). Humoral and cellular responses after a third dose of BNT162b2 vaccine in patients treated for lymphoid malignancies. MedRxiv, 2021.07.18.21260669. https://doi.org/10.1101/2021.07.18.21260669.
4. Roeker, L. E., Scarfo, L., Chatzikonstantinou, T., Abrisqueta, P., Eyre, T. A., Cordoba, R., … Patel, M. (2020). Worldwide Examination of Patients with CLL Hospitalized for COVID-19. Blood, 136(Supplement 1), 45–49. https://doi.org/10.1182/blood-2020-136408.
5. Brosh-Nissimov, T., Orenbuch-Harroch, E., Chowers, M., Elbaz, M., Nesher, L., Stein, M., … Wiener- Well, Y. (2021). BNT162b2 vaccine breakthrough: clinical characteristics of 152 fully vaccinated hospitalized COVID-19 patients in Israel. Clinical Microbiology and Infection, 27(11), 1652–1657. https://doi.org/10.1016/j.cmi.2021.06.036.
6. Karataş, A., İnkaya, A. Ç., Demiroğlu, H., Aksu, S., Haziyev, T., Çınar, O. E., … Göker, H. (2020). Prolonged viral shedding in a lymphoma patient with COVID-19 infection receiving convalescent plasma. Transfusion and Apheresis Science, 59(5), 102871. https://doi.org/10.1016/j.transci.2020.102871.
7. Interim Public Health Recommendations for Fully Vaccinated People.
   and Respiratory Diseases (NCIRD), Division of Viral Diseases. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/fully-vaccinated-guidance.html.
8. Sun, C., & Wiestner, A. (2021). Can Immunocompetence Be Restored in Chronic Lymphocytic Leukemia? Hematology/Oncology Clinics of North America, 35(4), 827–845. https://doi.org/10.1016/j.hoc.2021.03.010.
9. Study from The Leukemia & Lymphoma Society Shows COVID-19 Vaccine is Safe but 25% Of Blood Cancer Patients Do Not Produce Detectable Antibodies. (Leukemia & Lymphoma Society). July 22, 2021. https://www.lls.org/news/study-leukemia-lymphoma-society-shows-covid-19-vaccine-safe-25-blood- cancer-patients-do-not.
10. Lindoso, L., Astley, C., Queiroz, L. B., Gualano, B., Pereira, R. M. R., Tannuri, U., … Silva, C. A. (2021). Physical and mental health impacts during COVID-19 quarantine in adolescents with preexisting chronic immunocompromised conditions. Jornal de Pediatria. https://doi.org/10.1016/j.jped.2021.09.002.
11. Al-Rahimi, J. S., Nass, N. M., Hassoubah, S. A., Wazqar, D. Y., & Alamoudi, S. A. (2021). Levels and predictors of fear and health anxiety during the current outbreak of COVID-19 in immunocompromised and chronic disease patients in Saudi Arabia: A cross-sectional correlational study. PLOS ONE, 16(4), e0250554. https://doi.org/10.1371/journal.pone.0250554.
12. Bar-On, Y. M., Goldberg, Y., Mandel, M., Bodenheimer, O., Freedman, L., Alroy-Preis, S., … Milo, R. (2021). Protection against Covid-19 by BNT162b2 Booster across Age Groups. New England Journal of Medicine, 385(26), 2421–2430. https://doi.org/10.1056/NEJMoa2115926
13. ttps://www.lls.org/news/largest-study-date-demonstrates-most-blood-cancer-patients-benefit-third- primary-dose-mrna, last accessed: 08.02.2022
14. Zomerdijk, N., Jongenelis, M., Yuen, E., Turner, J., Huntley, K., Smith, A., … Short, C. E. (2021). Experiences and needs of people with haematological cancers during the COVID‐19 pandemic: A qualitative study. Psycho-Oncology, pon.5819. https://doi.org/10.1002/pon.5819.
15. Zomerdijk, N., Jongenelis, M., Short, C. E., Smith, A., Turner, J., & Huntley, K. (2021). Prevalence and correlates of psychological distress, unmet supportive care needs, and fear of cancer recurrence among haematological cancer patients during the COVID-19 pandemic. Supportive Care in Cancer, 29(12), 7755–7764. https://doi.org/10.1007/s00520-021-06369-5.
16. https://www.nhs.uk/conditions/coronavirus-covid-19/people-at-higher-risk/who-is-at-high-risk-from- coronavirus/, last accessed: 11.02.2022