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Take a look at a selection of our recent media coverage:

Harnessing the potential of bispecific antibodies in blood cancer care and beyond

16th February 2024

Bispecific antibodies are following hot on the heels of CAR T-cell therapies and paving the way for more accessible and timely treatment for patients with life-limiting diseases such as cancer. Saša Janković finds out more.

Bespoke, personalised blood cancer treatment was revolutionised by the approval of the first chimeric antigen receptor (CAR) T-cell therapy in 2017, and they continue to offer an improved quality of life for many patients.

More recent advancements have taken this to the next level, with off-the-shelf alternatives emerging from the development pipeline. Their name? Bispecific antibodies.

These are next generation monoclonal antibodies (mAbs). While typical mAbs target one epitope, bispecific antibodies have two distinct binding domains that can bind to two antigens or two epitopes of the same antigen simultaneously, causing multiple physiological or anti-tumour responses.

As a result, the treatment may act like a combination of two mAbs, but drug developers need to manufacture only one molecule, and patients may need only one antibody treatment.

And their benefits don’t end there.

Development milestones

Bispecific antibodies have been in development for several decades, and as of August 2023 there were approximately 160 in clinical trials and a further 460 in pre-clinical development.

Over 85% of bispecific antibodies in clinical trials are aimed at cancer therapeutics, but others are focused on chronic inflammatory, autoimmune, and neurodegenerative diseases; vascular, ocular and haematologic disorders; and infections.

‘Bispecific antibody therapies show promise and encouraging outcomes to date,’ says Dr Harriet Walter, associate professor of medical oncology and honorary consultant medical oncologist at the University of Leicester, and a medical advisor at Cancer Research UK.

‘We have seen particular success in haematological indications including non-Hodgkin lymphoma and myeloma, including in the post-transplant and CAR T-cell populations.’

In addition, research into bispecific antibodies has shown other promising results. ‘We are seeing encouraging developments in the treatment of certain solid tumours, with US Food and Drug Administration and European Medicines Agency (EMA) approval of tebentafusp-tebn for HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma’, says Dr Walter.

‘Tarlatamab in the treatment of small cell lung cancer has also shown impressive activity in the relapsed setting, with response rates of 40% and median overall survival of over 14 months in the phase 2 DeLLphi-301 trial, far exceeding historical treatment pathways, [and] the Phase 3 trial is ongoing.’

The list of recent approvals and recommendations for this drug class is extensive and includes:

Also on the horizon is Regeneron’s odronextamab, which is currently entering Phase 2 and 3 trials for R/R follicular lymphoma; and Amgen’s small cell lung cancer treatment tarlatamab – a bispecific T-cell engager class of artificial bispecific monoclonal antibodies that are being investigated for use as anti-cancer drugs.

CAR T versus bispecific antibodies

A clinician’s choice of CAR T-cell therapy versus bispecific antibodies depends on the characteristics of the disease being treated and the treatment’s approved indications, as well as the health of the patient.

CAR T-cell immunotherapy involves the extraction of T-cells from the patient, genetic modification of these cells in a laboratory setting to express the CAR, and then reinfusion of the engineered T-cells back into the patient to seek out and eliminate cells expressing the target antigen.

CAR T-cell product is given on a one-time basis, usually involving the patient travelling to a CAR T-cell therapy centre and remaining there for around a month due to the time required to manufacture the T-cells.

Dr David Tucker, substantive consultant haematologist leading the haematology Clinical Trials Unit at the Royal Cornwall Hospital, who is also the regional lead for non-malignant haematology research for the National Institute for Health Research (NIHR) clinical research network, has conducted seven clinical trials on bispecifics.

He says, in his practice, ‘CAR T therapy has a delay because patients have to have T-cells removed and sent to US where they are bio engineered before being returned to the patient, which can take three to six weeks’.

For a patient who needs treatment quickly, this may not be a viable option.

Another drawback to CAR T-cell therapy is that the sites that administer CAR T tend to be in bigger cities, ‘so for patients in far-flung places, or who are older and ill with cancer, travelling is no mean feat’, Dr Tucker adds.

A timely and accessible option

The off-the-shelf nature of bispecific antibodies means they can offer a timelier and more accessible alternative. They are administered as drugs, typically through intravenous infusion, as ongoing treatment often needing to be administered over a period of a year or more.

‘Bispecific antibodies are readily available, readily accessible, and NICE-approved in the UK to be used in district general hospitals across the country in haemato-oncology units. [They are] administered by the same nurses who would normally give chemotherapy’, Dr Tucker says.

Dr William Townsend, consultant haematologist at University College Hospital London and an advisor to the charity Lymphoma Action, says, bispecific antibodies could ‘potentially benefit more patients than CAR T-cell therapy because they enable treatment to be started sooner, and at locations that are more convenient for patients’.

What’s more, from a patient perspective, Dr Walter says: ‘Hospitalisation requirements and lower risk of severe cytokine release syndrome and neurological toxicity with bispecific therapies also confer potential benefits.’

And another perceived benefit is ‘the flexibility to potentially combine different bispecific constructs and target multiple-target tumour antigens and effector cells’, as well as ‘the ability to interrupt dosing if required due to toxicity’, she adds.

Research is also looking at how to harness the potential of bispecific antibodies in combination with other chemo-immunotherapeutic approaches to target unmet needs.

‘Despite ongoing waves of innovation in oncology, there remain significant unmet medical needs for patients’, says Edmond Chan, senior director, Europe, Middle East and Africa (EMEA) therapeutic area lead, haemato-oncology at Janssen EMEA. ‘For example, multiple myeloma remains incurable and with each line of additional therapy, patients face shorter remissions and more frequent relapses.

‘Another example is lung cancer, which is Europe’s biggest cancer killer, causing more deaths than breast cancer and prostate cancer combined. Of all lung cancers, non-small cell lung cancer accounts for around 85% of cases, where patients often face poor outcomes as they become resistant to standard treatments.’

While bispecific antibodies might not be suitable for everyone, healthcare professionals having another potential option in the treatment arsenal is certainly advantageous.

Current challenges and research opportunities

While their benefits cannot be ignored, there remain some unavoidable – for now – downsides to bispecific antibodies, including the obvious point of not yet having long-term data.

‘Although bispecifics are a very exciting development I don’t think at the moment they’re in a place to replace CAR T-cell therapy because we don’t yet have data that shows they have a curative effect, and we also don’t have long-term data on survival,’ says Dr Tucker.

‘At the moment I wouldn’t say that they were a substitute, but they can be a useful alternative for patients who are perhaps a bit frail or are unable or unable to travel or receive CAR T-cell therapy for some other reasons.’

Dr Walter adds that one of the major challenges is understanding how best to sequence bispecific antibodies with other approaches, including CAR T-cell therapies, particularly in haematological indications where both are approved.

She says working out ‘who benefits most from which approach and at what point in their disease trajectory’ is particularly important where both approaches are directed against the same tumour antigen, since ‘we know that antigen escape is one mechanism of resistance that can occur’.

‘Other potential barriers lie in the risks associated with stimulation of the immune system, which we also need for these agents to work’, Dr Walter continues.

‘However, with increasing knowledge of the toxicity profiles, mitigation strategies, such as step-up dosing and pre-treatment with steroids, this risk is significantly reduced.’

There are also perceived barriers to the success of bispecific antibodies in solid tumours.

Dr Walter says these are around ‘identification of suitable target antigens, avoiding the inevitable adverse effects on normal tissues, and potential limited access of bispecifics to the tumour site due to disordered neovasculature and stromal tissue as well as “cold” tumours’.

However, she adds that ‘approaches using, for example, T-cell stimulating vaccines are currently being explored’.

Raising awareness of bispecific antibodies

Despite increasing access, the awareness of, and confidence in, bispecific antibody treatment on the part of patients and healthcare professionals remains an additional hurdle to its adoption.

‘The challenge we face now is gathering experience and empowering doctors in district general hospitals who wouldn’t have experienced bispecific antibodies to have the confidence to use them’, says Dr Tucker. ‘We need to give them some education and training and reassurance that it’s safe to do so.’

Involving the patient and their families at every step of the process and ensuring they fully understand their treatment is also imperative.

‘We bring the patient along very closely – for example with regular meetings with the myeloma patient associations in Europe – to work out what we can help them to build for the patient so they will better understand the benefits and risks of these new therapies and how it is going to change their life,’ says Mr Chan.

‘We also work with European patient associations in the development stage of clinical trials to make sure that we are explaining things properly to the patients – including things like consent forms – to ensure that we are doing everything we can to make sure that patients are well looked after.’

Future trajectory

All things considered, experts agree that the future looks bright for bispecific antibodies – as well as for the patients who will benefit from them.

Dr Walter says the high response rates seen with bispecific therapies, and increasing long term safety and efficacy data, means ‘we are now seeing these agents being incorporated earlier in the treatment paradigms with the aim of improving outcomes earlier in the treatment pathway [and] we also assume these treatments work best in the setting whereby effector cells are least likely to be deleted or exist in an “exhausted state”.’

Dr Tucker agrees, saying: ‘I think once bispecific antibodies get fully licensed and approved, we will see them in widespread use at least after second line treatment, and moved up the sequence for use either in combination with first line chemotherapy, or second line chemotherapy, or even using them in on their own or with a novel agent like lenalidomide. They might even end up replacing the monoclonal antibodies such as rituximab or obinutuzumab.’

He adds: ‘We don’t yet know where they’re going, where is the right place to use them, or whether you can use them more than once. But they’re showing such efficacy that I think they may well change our frontline management of high grade and low-grade lymphoma if they appear to be well tolerated and effective.

‘I think they will be the most impactful treatment change since CAR T-cell therapy was approved.’

Undoubtedly, much more research, development and clinical applications of bispecific antibodies can be expected.

The FDA is already talking up what it calls ‘a dizzying array’ of potential formats for multispecific antibodies, which can target multiple antigens simultaneously and, it says, ‘may lead to treatments for diseases with no or few therapies’.

‘With expanding indications and increased knowledge of how best to use these antibodies, as well as new combination approaches, there is much still to learn and I think we see this landscape evolve over the next few years’, concludes Dr Walter. Watch this space.

Managing blood cancer: Claire Harrison on ruxolitinib for polycythemia vera

13th December 2023

The recent UK approval of ruxolitinib for the blood cancer polycythaemia vera marks a significant milestone in tackling unmet need for an under-represented patient population. Here, consultant haematologist Professor Claire Harrison speaks to Rod Tucker about ongoing challenges for the condition’s management, how this latest approval will benefit patients and clinicians, and other key research in the pipeline.

Ruxolitinib is a Janus kinase 2 (JAK2) inhibitor with diverse indications covering conditions such as eczema, psoriasis, vitiligo and myelofibrosis.

Most recently, in the UK at least, it has been added to the treatment arsenal for the rare blood cancer polycythaemia vera (PV) after its recommendation in October 2023 by the National Institute for Health and Care Excellence (NICE).

Professor Claire Harrison, consultant haematologist, professor of myeloproliferative neoplasms at Guy’s and St. Thomas’ NHS Foundation Trust in London, UK, has dedicated much of the last decade to researching ruxolitinib for use in PV and was instrumental in securing NICE’s endorsement.

‘It’s [a good] example of following a scientific story from discovery of the mutation, development of the drug, testing it in a more severe but related condition (myelofibrosis) then putting it into second line for PV,’ she says.

Despite the approval, there’s still work to be done to achieve the next ambition of ruxolitinib being approved for first-line use in PV. And Professor Harrison is on hand to get the ball rolling.

Diagnosing and managing polycythaemia vera

Today, diagnosing PV is much easier than when Professor Harrison first started as a consultant in 2001.

Previously, the diagnosis was arrived at following a series of tests to exclude all other possible causes of a patient’s symptoms and abnormal blood count. But after the description of a JAK2 mutation which is present in 97–98% of patients with PV, the diagnosis can be arrived at much more quickly.

‘This particular mutation for which it’s very easy to test for. It’s a cheap test and, for the most part, if it’s present, the patient has either got PV or one of the family of conditions, or it has very low levels of mutations but is likely to change into that,’ Professor Harrison says.

In general, the lay perception of a cancer diagnosis is that it represents a death sentence, and it becomes difficult to assuage patients of this fear.

While PV is incurable and lowers life-expectancy, it is not usually life-threatening, although Professor Harrison says some patients do present with life-threatening blood clots.

‘It’s a cancer but some low-risk patients we just treat with aspirin and phlebotomy, so removing blood,’ she says. ‘So that’s quite tricky saying “you’ve got cancer, but all we’re going to give you is an aspirin and take a pint of blood off you”, and other patients we do give treatments to, but we have limited options.’

Moreover, while these treatments do provide a clinical benefit in some patients, they frequently fail to alleviate symptoms.

This has become abundantly clear from the findings of the ongoing prospective REVEAL study. This showed that patients with PV experience symptoms that affect their quality of life and lead to work productivity impairments with an overall negative impact on their lives.

‘So, 80% of patients will complain of fatigue,’ Professor Harrison says. ‘It’s PV, it’s not a nothing condition: 20% of patients have to give up work or reduce their working time, others do die of the condition and the average life-expectancy is probably 15 to 20 years.’

Professor Harrison also highlights poor awareness of PV. ‘What patients would say, probably, is that people don’t understand the condition, GPs don’t understand the condition and their employers don’t understand the condition. It takes up a lot of their time and it has a big burden on their quality of life.’

She hopes that greater awareness of the condition will make it easier for people to support and make adaptations for this patient group.

Addressing unmet needs in PV

There haven’t been any new treatments for PV in around 20 years, with hydroxyurea and interferon alpha having long been the two options.

But that all changed with the description of the mutation. Professor Harrison says that after first helping with diagnosis, these learnings aided the development of drugs that could target the downstream effects of that mutation, principally JAK inhibitors.

‘These were first tested and used in more aggressive conditions in the family such as myelofibrosis. But with the advent of these drugs and their use in PV, we have been able to show that we can address some of the other unmet needs for patients,’ she says.

‘I could comment on how disappointing it is that the UK is five years behind the rest of Europe in the approval of ruxolitinib for PV, but I would prefer to celebrate that it’s a really important milestone for patients that they have an alternative therapy.’

This is particularly important as resistance or intolerance to treatments can develop in some patients, and there are other side effects and contraindications that mean traditional treatments may not be suitable.

‘An important side effect of hydroxyurea, which is also a side effect of ruxolitinib, is skin cancer,’ says Professor Harrison. ‘That’s something that we need to manage very carefully. If a patient has a skin cancer on hydroxyurea, we will sometimes change the therapy.

‘Interferon does cause quite serious mood disturbance – sometimes suicidal ideation – so it can’t really be used in patients who’ve got a significant history of anxiety or depression.

‘Similarly, [hydroxyurea] can’t be used for the 20% of patients below the age of 40 who might want to conceive a child. But we have the option to alternate between the first-line therapies.’

Emerging benefits of ruxolitinib

One of the key studies that led to the approval of ruxolitinib for PV in the UK was MAJIC-PV. This phase II trial, for which Professor Harrison was the lead author, randomised patients to either ruxolitinib or best available care in those intolerant or resistant to hydroxyurea, which is the current standard care therapy.

What was clear from MAJIC-PV was the superiority of ruxolitinib, with 43% of patients achieving a complete response based on several haematological criteria compared with only 26% of those receiving current best practice care.

While ruxolitinib does not cure PV, the MAJIC-PV trial provided reassurance that over five years no new longer-term safety issues emerged, Professor Harrison notes.

The trial also uncovered several additional biological actions of the drug. During the study, researchers measured the amount of abnormal JAK2 present in patients. This enabled clinicians to determine whether treatments had any effect on the aberrant mutations that were present.

Surprisingly, in those assigned ruxolitinib, there was a reduction in the level of this mutation.

As such, the MAJIC-PV study hinted at a mutation-specific effect of the drug which hadn’t previously been observed. Furthermore, this reduction in the level of abnormal JAK was associated with an increased life expectancy and a reduction in PV-related complications for patients.

‘Interestingly, when we were using the drug to treat patients with myelofibrosis, colleagues in Italy were reporting that their patients who had myelofibrosis but had the autoimmune condition alopecia, the hair was coming back,’ Professor Harrison adds. This hints at the wider benefits of ruxolitinib as an anti-inflammatory drug which is being harnessed in for example the treatment of eczema.

Delving deeper, Professor Harrison also describes how in research by colleague Adam Mead ruxolitinib appeared to modify PV at the stem cell level using research tools enaling the analysis of mutations at a single cell level.

Ruxolitinib as a first-line option?

Despite MAJIC-PV showing that ruxolitinib reduced levels of the abnormal JAK mutations, the current NICE approval recommends that the drug is used second-line for patients who either become resistant to or intolerant of hydroxyurea.

Notwithstanding this restriction, Professor Harrison still feels that it is important for patients to have access to ruxolitinib as another treatment option, either because of contra-indications or adverse effects from the currently available drugs.

Another consideration is the issue of drug resistance. ‘All of the available drugs are generally effective for the majority of patients, but over time, around 20–25% of patients will become resistant to that drug,’ she explains.

As a result, relying on a single drug isn’t the most effective way of controlling a patient’s blood count over time.

Encouraged by the findings from MAJIC-PV, a further phase III open-label trial, MITHRIDATE, for which Professor Harrison is the chief investigator, is starting to enrol patients.

It is designed to compare ruxolitinib with either hydroxyurea or interferon alpha as first-line therapy for high-risk PV patients.

Ruxolitinib also has a powerful effect on disease related symptoms for example patients with PV experience pruritus (itching) which can be extremely disabling, and the drug has a big impact on this troublesome symptom.

Although it is too early to draw any conclusions, Professor Harrison is hopeful that the MITHRIDATE trial will demonstrate the advantages of using ruxolitinib as a first-line treatment option and perhaps offer further insight into the drug’s disease-modifying properties.

Future treatment developments

While the introduction of JAK inhibitors such as ruxolitinib are a welcome addition to a clinician’s arsenal in the treatment of PV, Professor Harrison believes that future treatments need to focus on the off-target effects of these drugs such as immune suppression.

Although the development of JAK mutation-specific therapies in PV would be an advantage, Professor Harrison is of the opinion that it is just as important to improve understanding of how and when to use ruxolitinib in patients with PV.

Alongside the potential development of mutation-specific drugs, there is increasing interest in immune-mediated therapy.

‘I think we’ve had this massive step forward with description of molecular markers and therapies targeting JAK. We’ll probably go to treating PV earlier, and treating with a disease-modifying therapy,’ she concludes.

But focusing on the latest developments, Professor Harrison believes the introduction of innovations such as ruxolitinib would not have been possible without the support of various charities such as MPN Voice and Blood Cancer UK, as well as various academic centres and companies such as Novartis.

Working collaboratively, it has been possible to clearly demonstrate that ruxolitinib can go a long way towards helping to relieve the symptom burden of patients living with polycythaemia vera and improve quality of life for this under-represented patient population.

Positive CHMP opinion for momelotinib use in myelofibrosis patients with anaemia

20th November 2023

The Janus kinase (JAK) inhibitor momelotinib has received a positive opinion from the European Medicines Agency‘s Committee for Medicinal Products for Human Use (CHMP) for use in certain myelofibrosis patients, its manufacturer GSK has announced.

Momelotinib has been recommended for the treatment of disease-related splenomegaly or symptoms in adult patients with moderate-to-severe anaemia who have primary myelofibrosis, post polycythaemia vera myelofibrosis or post-essential thrombocythaemia myelofibrosis and who are JAK inhibitor naive or have been treated with ruxolitinib.

If approved, momelotinib (proposed brand name Omjjara) would be the only medicine in the European Union specifically indicated for both newly diagnosed and previously treated myelofibrosis patients with moderate-to-severe anaemia that addresses splenomegaly and symptoms.

Nina Mojas, senior vice president, oncology global product strategy at GSK, said: ‘Momelotinib has a differentiated mechanism of action that may address the significant medical needs of myelofibrosis patients, especially those with moderate to severe anaemia.

‘The vast majority of myelofibrosis patients will develop anaemia, causing them to require transfusions and leading a notable proportion to discontinue treatment.

‘This positive CHMP opinion is a significant step in bringing momelotinib to patients in the EU with this difficult-to-treat blood cancer.‘

Statistically significant response for momelotinib

The positive opinion was based on the results of the pivotal MOMENTUM trial, which evaluated the safety and efficacy of momelotinib versus danazol for the treatment and reduction of key manifestations of myelofibrosis in an anaemic, symptomatic, JAK inhibitor-experienced population.

All primary and key secondary endpoints were met, and momelotinib demonstrated a statistically significant response with respect to constitutional symptoms, splenic response and transfusion independence compared to danazol at Week 24.

Momelotinib was also associated with favourable safety at Week 48 in a follow-up analysis.

The CHMP recommendation was also supported by data from a subpopulation of adult patients with moderate-to severe-anaemia (haemoglobin <10 g/dL) from the SIMPLIFY-1 phase 3 trial.

This evaluated the efficacy and safety of momelotinib versus ruxolitinib in myelofibrosis patients who had not received a prior JAK-inhibitor therapy.

It found that in JAKi-naive patients with myelofibrosis, 24 weeks of momelotinib treatment was non-inferior to ruxolitinib for spleen response but not for symptom response. Momelotinib treatment was also associated with a reduced transfusion requirement.

In these clinical trials, the most common adverse reactions were diarrhoea, thrombocytopaenia, nausea, headache, dizziness, fatigue, asthenia, abdominal pain and cough.

A decision on EU marketing authorisation is expected for momelotinib by early 2024.

Momelotinib was approved by the US Food and Drug Administration in September 2023 under the brand name Ojjaara. It is currently not approved in any other market.

Ruxolitinib approved by NICE for treatment of polycythaemia vera

25th September 2023

The kinase inhibitor ruxolitinib (brand name Jakavi) has been recommended in draft guidance by the UK’s National Institute for Health and Care Excellence (NICE) for the treatment of patients with the blood cancer polycythaemia vera (PV), its manufacturer Novartis has announced.

The endorsement covers the approved oral indication of ruxolitinib for the treatment of PV in adults who are unable to tolerate the standard treatment of hydroxycarbamide, or when the condition is resistant to it.

Commenting on the approval, Dr Claire Harrison, consultant haematologist at Guy’s and St Thomas’ NHS Foundation Trust in London, said: ‘There is a significant unmet need for people with polycythaemia vera in England and Wales, who live with a large symptom burden as a result of their condition.

‘[This] decision is a step in the right direction for providing additional treatment options that reduce the burden of these symptoms and improve disease progression, in this under-represented patient population.‘

Jon Mathias, co-chair of MPN Voice – a charity that supports and advocates on behalf of PV patients – added: ‘We welcome this recommendation from NICE, as polycythaemia vera can be an extremely debilitating illness that has a significant impact on patients’ lives in terms of day-to-day symptoms.

‘It affects not only patients but also their families and carers and turns many everyday tasks into major hurdles. Ruxolitinib addresses a significant unmet need in patients who cannot tolerate or no longer respond to HC/HU.‘

Ruxolitinib efficacy in polycythaemia vera

In 2015, a phase 3 randomised trial showed that in patients with PV who had an inadequate response or unacceptable side effects from hydroxycarbamide, ruxolitinib was superior with respect to controlling the haematocrit, reducing the spleen volume and improving associated symptoms.

Moreover, ruxolitinib has also been shown to be efficacious and well tolerated in PV patients who were previously treated with interferon.

PV is rare blood cancer affecting the bone marrow. A myeloproliferative disorder, it involves uncontrolled red blood cell production resulting in an elevated red blood cell mass. The condition affects an estimated 1,130 people in the UK every year and the underlying cause of the disease is related to dysregulation of the JAK-STAT pathway. Typically, patients have an elevated haematocrit, leading to blood thickening, increasing the risk of blood clots, as well as higher white blood cell and platelet count.

Ruxolitinib is an inhibitor of the JAK 1 and JAK 2 tyrosine kinases and was recently approved in the UK in a topical form as a treatment for non-segmental vitiligo in adults and adolescents with facial involvement.

Blood cancer patients have lower antibody response to Omicron after third COVID vaccine dose

3rd February 2022

Blood cancer patients who have received a third vaccine dose continue to produce a limited antibody response to the Omicron variant

Patients with blood cancer generate a reduced neutralising antibody response to the Omicron variant even after a third vaccine dose, according to a study by a UK team of researchers.

Patients with cancer who become infected with COVID-19 are known to have a higher mortality risk compared with those without the disease. However, as cancer patients were excluded for the pivotal COVID-19 vaccine trials, there was always some uncertainty over the ability of such patients to mount a sufficient neutralising antibody response to vaccination.

Available data has shown how blood cancer patients such as those with chronic lymphocytic leukaemia, have an impaired antibody response to vaccination. A further problem is that with the emergence of variants of concern which are capable of immune escape, the antibody response might be even worse.

In fact, such fears appear to have been realised with one study reporting that blood cancer patients were more likely to have undetectable neutralising antibodies compared to those with solid cancers against both the wild-type and the Alpha, Beta and Delta COVID-19 variants of concern.

Despite these findings, administration of a third COVID-19 vaccine appears to boost the neutralising antibody response for those with solid tumours but the response remains muted in blood cancer patients. For instance, one study found that following the third dose, only 54% had detectable neutralising antibodies against Delta and 54% against Beta.

For the present study, the researchers focused their attention on the Omicron variant and sought to examine the immune response generated in response to this variant in those with both solid tumours and blood cancers. The team used a live-virus micro-neutralisation assay to evaluate the response to Omicron following three doses of COVID-19 vaccines in participants enrolled in the CAPTURE study, which was a prospective and longitudinal study of patients with cancer.

Blood cancer patients’ response to third vaccine dose

The researchers enrolled 199 patients, 58% of whom had a solid cancer and the remainder a blood cancer, all of whom had received a third COVID-19 vaccine dose. They also included a matched sample before the third dose which included 179 patients (115 with solid cancers and 84 with a blood cancer).

After two COVID-19 vaccine doses among the 100 patients with solid cancers, 37% generated detectable neutralising antibodies against Omicron. In contrast, among 79 patients with a blood cancer, only 19% generated a detectable response to Omicron after two vaccine doses.

With a third vaccine dose, among the 115 patients with a solid cancer, neutralising antibodies to Omicron were detected in 90% of patients. However, for the 84 patients with a blood cancer, after a third vaccine dose, Omicron neutralising antibodies were only detectable in 56% of patients.

Based on these findings, the authors concluded that while a third vaccine dose enabled those with solid cancers to produce a robust neutralising antibody response to Omicron, only half of those with a blood cancer were able to mount a sufficient response, highlighting the need for a possible fourth dose in this patient cohort.

Fendler A et al. Omicron neutralising antibodies after third COVID-19 vaccine dose in patients with cancer Lancet 2022