COVID-19 Vaccination in Haematology Patients: An Australia and New Zealand Consensus Position Statement
Australia and New Zealand have achieved very good control of community spread of SARS-CoV-2 during the global pandemic due to highly effective public health interventions.(1, 2) As of 20 January 2021, Australia had recorded 22,201 local cases with 909 total fatalities(3) and New Zealand had reported 1044 local cases with 25 fatalities.(4)The availability of effective vaccines offers an opportunity to consolidate this successful control and requires consideration of their application to key vulnerable populations including those with haematological disorders.
Haematological malignancies account for approximately 11% of all cancers in Australia and New Zealand.(5)Patients with lymphoid malignancies, including chronic lymphocytic leukaemia (CLL) and multiple myeloma, recipients of allogeneic stem cell transplantation and of potent B- and T-cell depleting therapies are particularly vulnerable to serious viral infections.(6-9) Haematology patients are often severely immune compromised due to their underlying disease and/or associated therapy, and experience higher rates of infection than age-matched controls.
Adults with haematological malignancies are reported to be at high risk of progression to severe disease and death from COVID-19 with an estimated mortality of 36% or greater, comparable to the mortality rate of aged care residents.(10-13) While mortality risk in paediatric patients (estimated at 4%) is lower, it is much higher than in healthy children.(11)
Patients with haematological malignancies, including lymphoid disorders, multiple myeloma, acute myeloid leukaemia and myelodysplastic syndrome appear to be at highest risk of mortality.(10, 11) Among those with lymphoid malignancies who acquire COVID-19, hospitalisation rates are up to 90% and intensive care admission rates 35%.(14) CLL patients who had previously received immunochemotherapy have a mortality of up to 60%. In a multi-national cohort of patients with multiple myeloma and COVID-19 infection, the COVID-19-related mortality rate was 33% with geographical variation from 27-57% of hospitalised patients.(12) In a myelofibrosis population study, the COVID-19 mortality was 48% (15). Limited data suggest that chronic phase chronic myeloid leukaemia patients on tyrosine kinase inhibitors with COVID-19 have mortality rates comparable to the general population.(16),(17) In myelofibrosis additional risk factors of mortality include discontinuation of ruxolitinib at COVID-19 diagnosis, possibly due to rebound inflammation.(15)
Patients with benign haematological disorders have varying outcomes depending on the underlying disease and associated co-morbidities (18-21). Patients with sickle cell disease appear to be at particular risk with an age standardised mortality ratio of 7.7 times (20).
In patients with haematological malignancies, COVID-19-related mortality is not always related to recent therapy of the underlying malignancy (11, 12, 14). Risk factors for mortality include age >60 years, active or progressive disease, ECOG performance score ≥2, absolute lymphocyte count ≤0.6 x 109/L, platelet count ≤40 x 109/L, an elevated LDH, and a raised C-reactive protein.(10, 11) In multiple myeloma additional predictors of include high risk cytogenetics (del17p, t(4;14), amp 1q or t(14;16) and renal disease.(12, 22) Furthermore, patients with haematological malignancies who recover from COVID-19 display distinct, prolonged immunological complications compared to those with solid organ malignancies who have similar rates to the general population.(23)
Impaired SARS-CoV-2 Clearance and Viral Evolution in Patients with Haematological MalignanciesPatients with haematological malignancies are unable to clear certain viruses (14, 24). Preliminary reports suggest that these patients when exposed to SARS-CoV-2 display heterogeneous humoral responses, an exhausted T cell phenotype and a high prevalence of prolonged virus shedding more so than patients with solid organ malignancies(23, 25). Therefore, these patients have an ongoing risk of recurrent infection and of onward transmission. Furthermore, preliminary data suggests that immunecompromised patients have the potential for accelerated viral evolution (25, 26). Vaccine Considerations
These data should inform future preventative efforts as Australia and New Zealand commence their vaccination campaigns. At time of writing there are two vaccines of relevance in Australia and New Zealand. The Pfizer/BioNTech SARS-Cov-2 vaccine is a first-in-class mRNA vaccine which in an international phase 3 study was administered to 43,448 participants aged 16 or older in a two dose regimen 21 days apart. The vaccine was 95% effective against symptomatic COVID-19 from seven days after the second dose. Efficacy was consistent across age, gender and ethnicity, and no serious safety concerns were reported. This trial included a small number of patients (n=76) with leukaemia or lymphoma as a co-morbidity, 36 of whom received the vaccine (27).
The AstraZeneca ChAdOx1 nCOV-19 vaccine is a replication-deficient chimpanzee adenoviral vectored vaccine given in a two dose regimen. In a pooled analysis across four studies with varying dosing, overall vaccine efficacy was 70.4% with no serious safety concerns reported.(28) In a subgroup of 8,895 participants who received two standard doses (as will be administered in practice), vaccine efficacy was 62%. Experience with viral vectored vaccines is limited with no evidence in haematology patients.
An alternative vaccine available internationally is the Moderna mRNA SARS-CoV-2 vaccine (mRNA-1273) which is another two dose regimen vaccine administered 28 days apart, shown in a phase 3 study to have an overall efficacy of 94%.(29) Other vaccines with potential future relevance in Australia and New Zealand include the Novovax vaccine NVX-CoV2373, the Janssen vaccine Ad26Cov2S and access to the COVAX facility.
None of these studies included immunocompromised patients, and we await studies to evaluate these vaccines specifically in haematology patients. Despite the lack of data, none of these are live vaccines and therefore pose no risk of COVID-19 transmission.
Acknowledging the paucity of prospective data, representative experts from the Haematology Society of Australia and New Zealand, have collaborated with Infectious disease specialists on this consensus position statement regarding COVID-19 vaccination in haematology patients in Australia and New Zealand. Broadly we consider that the following applies to all haematology patients:
4. Vaccination should be timed with the aim of achieving optimal protection at the earliest opportunity without compromising disease treatment outcomes. Where possible, vaccination should be completed at least two weeks before immunosuppressive treatment (31).
Patients with bleeding disorders, those receiving antiplatelet or anticoagulant therapy and those with thrombocytopenia may have an increased risk of bleeding at the injection site given the intramuscular route of administration (40).
Both viral infections, and immunisations against viruses have been implicated as potential “triggers” of immune thrombocytopenia (ITP)(41, 42). But immunisation induced ITP is very rare, and for most ITP patients the benefits of avoiding COVID-19 infection far outweigh the risks of disease flare from vaccination. Although treatments for ITP such as high dose steroids and anti-CD20 monoclonal antibodies may impair humoral responses to immunisation, no data exist specifically for this cohort. It is recommended that vaccination of ITP patients should be done in consultation with and under the supervision of a haematologist.
Splenectomised patients should be encouraged to stay on antibiotic prophylaxis as per standard recommendations. However, consideration must be given to the indication for splenectomy including haematological malignancies, sickle cell disease and thalassemia which are associated with increased mortality with COVID-19.
Some patients with these lymphoproliferative disorders may not necessarily require immediate chemotherapy or immunotherapy. However, significant delay in interventions in an attempt to achieve a potential increased immunological response is not recommended. This should be based on clinical discretion considering the risks and benefits to the patient (35).
Given the acute and urgent nature of a diagnosis of acute leukaemia, vaccination should not delay definitive therapy. For patients in remission, vaccination should be facilitated as soon as possible with consideration for thrombocytopenia and the associated risk of bleeding.
There are case reports of aplastic anaemia (AA) post-vaccination, and of recovered AA patients relapsing post vaccination.(43, 44) Conversely, it is likely that viral insults are a key trigger in the pathogenesis of many cases of AA.(45, 46)
Recent immunosupressive treatment in the setting of AA (typically anti-thymocyte globulin (ATG) and cyclosporin) is likely to markedly impair host immune response to vaccination. However, patients on maintenance cyclosporin more than six months post ATG and/or allogeneic haematopoetic stem cell transplantation do demonstrate responses to other routine vaccinations.(47)
The risk of COVID-19 infection still favours vaccination in AA, particularly those with additional risks for severe COVID-19 disease.(48)
Refer to the ANZTCT position statement available for guidance.
These statements will be regularly reviewed and updated as appropriate as further data on vaccines emerge hsanz web page
Authors: Cited in full document
The authors declare no conflicts of interest.
Myeloma Scientific & Advisory Group (MSAG)
The Australasian Lymphoma Alliance (ALA)
Chronic Lymphocytic Leukaemia Australian Research Consortium (CLLARC)
Plan to attend the ONLY official Highlights of ASH for synopses of the top hematology research presented at the 62nd ASH Annual Meeting and Exposition this past December. This meeting is your chance to discuss rapidly evolving developments in hematology with leading faculty in the field, discover new treatments for patients, and improve overall practice methods.
This year’s all-virtual experience will take place between March 1 and April 2 and will feature curated annual meeting content that is relevant to all regions in which ASH has historically presented, including North America, the Mediterranean, Asia-Pacific, and Latin America.
Review the preliminary program and register now!
Attendees will receive full access to the entire program and content on the virtual platform until April 2, including:
Have you listened to HSANZ President, Leanne Berkan's interview with Sunalie Silva in the limbic today?
She reflects on 2020 in terms of haematology, talks about what to expect in haematology in 2021, a little about HSANZ and gives a plug for our Blood 2021 conference in September in Adelaide.
Click this link for the podcast
It is with great excitement that we congratulate Vice Present and President Elect, Associate Professor Steven Lane from the QIMR Berghofer Medical Research Institute on winning the National Stem Cell Foundation of Australia Metcalf Prize.
Associate Professor Steven Lane wants to lift the survival rates of his leukaemia patients. He thinks the key could lie in the genetic fingerprints of the blood cancer stem cells that proliferate the disease.
Steven’s research has been funded by the National Health and Medical Research Council, CSL Centenary Fellowship, Cancer Australia, Leukaemia Foundation, Cure Cancer Australia, Gordon and Jessie Gilmour Trust, MPN Research Foundation, MPN Alliance of Australia, and others.
Read more about Steven’s work here. If you’d like to send your congratulations, his email address is here.
The Metcalf Prizes are named for the late Professor Donald Metcalf, AC, who transformed cancer treatment with his discoveries of critical molecules that tell stem cells to multiply and mature to boost the immune system.
The media release is below:
Using stem cell research to fight cancer has won two Australian researchers $55,000 each in the annual Metcalf Prizes for Stem Cell Research, awarded by the National Stem Cell Foundation of Australia.
Associate Professor Steven Lane of the QIMR Berghofer Medical Research Institute wants to lift the survival rates of his leukaemia patients. He thinks the key could lie in the genetic fingerprints of the blood cancer stem cells that proliferate the disease.
Steven is studying how these cells become resistant to treatment through genetic changes. He will use the knowledge to develop more effective and tailored therapies, both to prevent and treat potentially fatal relapses.
Dr Melanie Eckersley-Maslin—a new recruit of the Peter MacCallum Cancer Centre—believes the proteins which control the growth of cells in embryos could teach us how to stop the uncontrolled growth of cells in cancer.
The scientists have been recognised by the Foundation for their early-career leadership in stem cell research.
“Melanie Eckersley-Maslin and Steven Lane are taking two very different stem cell research approaches to understand, prevent and treat different types of cancer,” says Dr Graeme Blackman AO, the chairman of the Foundation.
The awards are named for the late Professor Donald Metcalf AC who, over a 50-year career, helped transform cancer treatment and transplantation medicine, paving the way for potential stem cell therapy in the treatment of many other conditions.
The 2020 Metcalf Prizes for Stem Cell Research will be formally presented by molecular biologist Professor Suzanne Cory AC FAA FRS at a special event in Melbourne on Monday 8 February 2021.
The NSCFA is an ATO-registered, tax-deductible health promotion charity dedicated to promoting the study and responsible use of stem cells to reduce the burden of disease.
The Foundation’s activities include:
The Foundation is led by an expert volunteer Board, with a diversity of scientific, medical and governance experience. The Chairman is Dr Graeme Blackman, AO, FTSE, FAICD.
The Board consults with leading stem cell scientists before committing funds to research and education initiatives.
More at website
Issue 52 of Lymphoma and Leukaemia Research Review
This issue begins with research reporting good tolerability of BR (bendamustine, rituximab) in patients aged ≥80 years with CLL, with efficacy and safety similar to that seen in younger patients as long as carefully adapted dosing is applied.
The PDF can be viewed here, and now you can also view the issue online.
Women currently working in the healthcare sector have a final opportunity to register their interest in a scholarship worth up to AUD$5,000 to support participation in an accredited leadership development program.
Funding must be apportioned promptly, and it is unsure when these grants will be available again. Find out more and register your interest by completing the Expression of Interest form prior to 5pm on Monday, 14 December 2020.
The phase I safety trial, called ENABLE, is part the of the Malaghan Institute’s research and development of a new version of CAR T-cell technology, in partnership with Wellington Zhaotai Therapies Limited. The trial will involve up to 12 participants with certain types of relapsed and refractory B-cell non-Hodgkin lymphoma who have exhausted other treatment options.
Malaghan Institute Clinical Director Dr Robert Weinkove says the production of CAR T-cells is a major step in the development of the Institute’s cell therapy capabilities.
“Chimeric antigen receptor T-cell therapies are being offered to treat certain types of B-cell lymphoma (lymph node cancer) in countries such as Australia and the UK. For this early phase safety trial of a new type of CAR T-cell therapy, we’ll be manufacturing the cells in the dedicated cell therapy suite at the Malaghan Institute in Wellington.
“Because the safety and effectiveness are not yet known, this will be a small trial for a limited number of participants. Nonetheless, this is a very exciting milestone, and we hope the experience and knowledge we gain from the ENABLE trial will help more New Zealanders benefit from CAR T-cell therapies in the future.”
Dr Weinkove says the trial will not be the right option for everyone, and it is important that patients speak with their specialist about their treatment options. “Referrals for the trial can only be accepted from haematologists or oncologists, who will be advised of the criteria and how to refer.”
Dr Weinkove says the trial is taking place at a single centre, to allow close monitoring of participants, but referrals from other hospitals will be considered. “With support from Leukaemia & Blood Cancer New Zealand, we hope to be able to provide travel and accommodation support for participants from outside our region.”
For the rest of the article, click here
Julian Grabek is one of HSANZ / LF's PhD recipients for 2021, and is showing his research skills already. His work is on Identifying subclones in early phase MPN that drive progression and leukaemic transformation
Myeloproliferative neoplasms (MPN) are clonal haematological disorders of stem cells. These stem cells undergo a mutation that drives an overproduction of blood cells. MPNs include
Throughout the course of the disease the stem cells are driven by specific mutations (JAK2, CALR and MPL) but over time additional genetic mutations are acquired leading to progression of the disease to either secondary myelofibrosis and bone marrow failure or acute myeloid leukaemia. These outcomes have limited treatment options and have a poor prognosis.
High risk stem cells with the potential to develop into leukaemia can be identified early in the disease but are often a “needle in a haystack” when compared to the rest of the MPN stem cells. By using cutting edge single cell technology Dr Grabek will separate each individual cell of the MPN stem cells. Through a combination of mutational analysis by novel nanopore technology and assessment of downstream gene signalling he will be able to determine the early stages of leukaemia development in these disorders. In future, he hopes to establish which treatments have the potential to arrest these early changes and prevent transformation to leukaemia.
for the article on the LF website, click here
HSANZ Member, Professor John Seymour, Director of Clinical Haematology at the Peter MacCallum Cancer Centre and Royal Melbourne Hospital, has been named as among the most influential in the world in the annual Highly Cited Researchers 2020 list
The list identifies scientists who have published papers ranking in the top 1% by citations by peers in their field over the past ten years. Among the 6,400 Highly Cited Researchers across 21 fields of the sciences there are 482 named in the clinical sciences section and 199 in immunology research.
See this article in the limbic for full story
HSANZ is pleased to be invited again to partner the American Society of Hematology for the Highlights of ASH series which will be taking place virtually in March 2021. All Members of HSANZ will be entitled to a discounted registration.
ASH is excited to share additional information in the coming weeks, but the regional meetings originally scheduled to take place in North America (January), the Mediterranean (February), Asia-Pacific (March), and Latin America (April) will be offered as as a collective virtual experience in March 2021. More information about the program and registration will be available in early 2021.
Meanwhile, here is the 2021 Highlights of ASH website. As soon as we know more, we will post it here.
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Tel: 02 8097 8114
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