“The outlook is improving all the time” – MMI Graham Jackson interview

MMI Graham Jackson interview 

People with multiple myeloma had a difficult pandemic but hope is on the horizon in terms of groundbreaking therapies becoming a reality. Danielle Barron speaks to Newcastle University’s Professor Graham Jackson about novel immunotherapies and the promise of CAR-T cells being realised 

A consultant haematologist specialising in haematological malignancies, particularly myeloma, lymphoma and acute leukaemias, Professor Graham Jackson works in Haematology/Oncology and Bone Marrow Transplantation at the Newcastle Hospitals NHS Foundation Trust and is a Professor of Clinical Haematology at Newcastle University. 

Professor Jackson will visit Ireland this month to speak at the Haematological Malignancies Update Day and prior to the meeting he spoke to Multiple Myeloma Ireland about how the Covid-19 pandemic had been especially tough for those with the condition.

“There is little doubt that Covid-19 has had a huge impact on multiple myeloma patients, not least because for two years or more they have had to shield and worry about infection. It’s no lie that people with multiple myeloma can have more problems with Covid-19 than the general population,” Jackson admits.

Yet learnings during this period as well as new advances mean the situation is more hopeful
than before as the virus continues to linger. Jackson notes that patients with untreated
multiple myeloma appear to be most at risk and those who have their disease under control
or in remission seem to do better than patients who have active disease. He notes, however,
that while patients with myeloma need at least three doses of a Covid-19 vaccine and initial
responses can be lower in myeloma patients “they might still be protective”. Vaccination has
certainly had an impact, if not at the same scale as it did in the general population, he says.

“In the UK over the last year we have seen far fewer myeloma patients getting into big
problems with Covid compared to the year before. There is room for hope and obviously we
now also have the antiviral drugs for Covid-19 that they are now offering in the UK which are
making a huge difference as well in immunocompromised patients.
“So, we can reassure myeloma patients that the virus is getting milder, the vaccines offer
some protection, and also myeloma patients are entitled to get antiviral or antibody therapies
which means that the outlook is more positive.”
The professor also notes that the pandemic may have inadvertently created some
advantages for myeloma patients – the advent of remote monitoring, for example. “Patients
no longer have to travel to the clinic if they want to talk to a physician, so it cuts down on
their travel time and having to be in a hospital around other sick people. I don’t think we will
go back to a model where you have to see a doctor every single time you need a review, we
will be happy to do this online.”

Meanwhile, in the background, scientific advances in multiple myeloma treatment have
continued, despite some disruption early on to clinical trials. Jackson notes that the
availability of the much-anticipated CAR-T cell therapy is “imminent”.
“We are very close to CAR-T cells being available for patients in the UK and Ireland, very close.” He adds that he remains as excited about the therapy as he was when he first learned of the highly positive results it was giving.
“All the promise of CAR-T cell therapy has been really confirmed in clinical trials and the data continues to be very, very positive. The response rates are still extraordinarily high and there is now evidence of good longevity of response. It has gone from being experimental to being potentially part of your therapeutic options, and I know that Dublin, like us here in Newcastle and the rest of the UK, are gearing up to start delivering that therapy to multiple myeloma patients. It will be truly transformational.”

Jackson is also enthused by the group of therapies known as the bispecific T-cell engager (BiTE) antibodies, which he says are also showing significant promise when it comes to treating multiple myeloma. These therapies harness the patient’s own T cells within their bodies to attack the myeloma cells, and many are in an advanced stage of development.

“These work in a slightly different way to CAR-T cells but the promise is almost as exciting,” he explains. “There is a lot of data to suggest that even patients even with heavily pretreated multiple myeloma can respond to T cell engagers.”

B-cell maturation antigen (BCMA), which is expressed on the plasma cell in multiple myeloma, has also become an important therapeutic target, and an antibody drug conjugate known as belantamab mafodotin (BM) has recently been approved by the US FDA. “This drug has some toxicities associated with it in terms of problems with the eyes but
again it is a single agent that is a very good treatment for multiple myeloma,” Jackson notes. He adds that Selinexor, a selective inhibitor of nuclear export, is another agent that has received widespread interest for its ability to impact how the multiple myeloma cell defends itself against chemotherapy and again, promising data for its use continues to grow.

CELMoDs [Cereblon E3 ligase modulators] are also looking promising, as they build on what
clinicians and researchers have learned from thalidomide, lenalidomide, and pomalidomide.
The bottom line is that outcomes in multiple myeloma are continually improving, Jackson
asserts, but he admits there are still some difficult to treat groups.
Patients with less favourable cytogenetic profiles fall into this category. “The more
complicated the genetic makeup of the plasma cells, the poorer those patients do in terms of
outcomes of treatment,” he says. “So while learning about the cytogenetics of their disease
can help us determine a patient’s prognosis, and has led to some improvements for those
patients, there is still quite a need for more improvements.” Likewise, patients who are older
and frailer can find the toxicities of the treatment “quite difficult to tolerate” and outcomes can
subsequently be poorer in this cohort.

Jackson is keen to emphasise that, despite the pandemic, therapeutic advances in multiple
myeloma treatment have continued and this is “encouraging” news for patients. “They are
going to have more and more options and treatment will get more complicated. There is still
some work to be done but for most patients the outlook is improving all the time.”