Chimeric antigen receptor (CAR) T-cell therapy is a treatment that uses genetically modified immune cells (T-cells) to treat myeloma. While clinical studies have demonstrated the strong efficacy of CAR T-cell therapies in this disease, many patients experience side effects that can persist for months or years after treatment.

To inform myeloma patients and the myeloma community about the long-term benefits and side effects of CAR T-cell therapies, Myeloma Patients Europe (MPE) will host the webinar on “Long-term outcomes of CAR T-cell therapy in myeloma” on Wednesday, 21 October at 16:00 CEST.

During this webinar you will hear about the long-term efficacy and safety data from clinical trials of CAR T-cell therapies in myeloma, and what recovery, long term monitoring and side-effect management may look like. This presentation will be given by Dr. Herman Einsele, from the University of Würzburg in Germany, who is a myeloma expert with extensive experience in CAR T-cell therapies.

You will also hear from David Williams, a myeloma patient and Myeloma UK (MUK) member, who received CAR T-cell therapy three years ago. David will share his experiences, including preparation, outcomes, side effects, and quality of life.

Dr. Herman Einsele is Full Professor of Internal Medicine and Director of the Department of Internal Medicine II, University Hospital Würzburg, Germany since 2004. Since 2018, he is the chair of the Specialized Working Group on Immune Therapies for Hematologic Disorders of the European Hematology Association (EHA).

Dr. Einsele is an expert in the field of myeloma with focus on CAR T-cell therapy, bispecific antibodies, adoptive immunotherapy and stem cell transplantation.

David Williams is a myeloma patient and part of the MPE member organisation Myeloma UK (MUK). He was diagnosed with myeloma in October 2022 and was admitted on the sponsored CAR T-cell therapy clinical trial called CARTITUDE. He has been in remission since October 2023.

David is almost retired and lives with his wife in Bristol, UK. He has a daughter and son and four grandchildren. Learn more about David’s story here.

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You can also watch the MPE ASH 2024 highlights webinar recording here.

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Myeloma Patients Europe (MPE) will attend the meeting to learn and share updates about the most significant developments in myeloma and AL amyloidosis. MPE will also meet with members, sponsors, European and US advocacy groups, myeloma doctors, researchers and other stakeholders to discuss ongoing projects and future collaborations.

Stay tuned to our social media accounts (Facebook, LinkedIn, Twitter) for the latest information during the conference. MPE will be filming and posting interviews with leading researchers throughout the Meeting.

MPE will also host an ASH highlights webinar on 18 December at 17:00 CET.

MPE´s Head of Medical Education and Scientific Engagement, Solène Clavreul, is also a co-author on a poster being presented on Sunday, 8 December. The poster is entitled Examining Discrepancies in Perspectives of Healthcare Providers and Patients With Relapsed/Refractory Multiple Myeloma on Novel Therapies Across Diverse Clinical Landscapes: An International Prospective Study. You can find further information here.

PROGRAMME HIGHLIGHTS

The programme for myeloma and AL amyloidosis this year is extensive and rich, with a range of research focusing on the science underlying myeloma and on the anti-myeloma effect of existing and new medicines. Given the extensive programme, it is difficult to summarise every presentation, but MPE believes the following myeloma and AL amyloidosis data will be of greatest interest to patients:

AL Amyloidosis

There will be several presentations on the treatment of AL amyloidosis. In particular, results of the ISAMYP study will be presented. The study conducted in multiples sites in France and Australia is evaluating the efficacy and safety of the combination of isatuximab, pomalidomide and dexamethasone (IsaPd), in AL amyloidosis patients with suboptimal response to previous therapy or at relapse.

• Efficacy and Safety of Isatuximab, Pomalidomide and Dexamethasone in Relapsed AL Amyloidosis: Interim Results of the Isamyp Phase 2 Joint Study from the IFM and ALLG. Click here for details. Monday, December 9, 2024: 3:30 PM (GMT-8)

Smouldering myeloma

There are few presentations of interest that will focus on the outcomes of patients with smouldering myeloma. In the years to come, it will be important to understand when it is best to start treatment. The Aquila study is investigating whether daratumumab monotherapy could delay progression to myeloma compared active monitoring in patients with high-risk smouldering myeloma and preliminary results will be presented during the meeting.

• Phase 3 Randomized Study of Daratumumab Monotherapy Versus Active Monitoring in Patients with High-Risk Smouldering Multiple Myeloma: Primary Results of the Aquila Study. Click here for details. Monday, December 9, 2024: 11:30 AM (GMT-8)

The CAR PRISM study is investigating, for the first time, the safety and efficacy of the use of Ciltacabtagene Autoleucel (cilta-cel), a BCMA-directed CAR T-cell therapy in patients with high-risk smouldering myeloma, without induction therapy, and will present the results observed in the first 6 patients of the study.

• Early Safety and Efficacy of CAR-T Cell Therapy in Precursor Myeloma: Results of the CAR-PRISM Study Using Ciltacabtagene Autoleucel in High-Risk Smouldering Myeloma. Click here for details. Monday, December 9, 2024: 4:30 PM (GMT-8)

Myeloma

There will be several talks dedicated to the treatment of newly diagnosed myeloma. As tolerance to treatment vary among patients, the IFM2017-03 study is investigating the efficacy and safety of the daratumumab, lenalidomide and dexamethasone combination without long term dexamethasone compared to a lenalidomide and dexamethasone combination with long term dexamethasone in a frail population of patients with newly diagnosed myeloma. Positive results may lead to a decreased use of dexamethasone and therefore an improved quality of life for patients.

• The IFM2017-03 Phase 3 Trial: A Dexamethasone Sparing-Regimen with Daratumumab and Lenalidomide for Frail Patients with Newly-Diagnosed Multiple Myeloma. Click here for details. Monday, December 9, 2024: 11:45 AM (GMT-8)

Some results of the MajesTEC-5 study on the addition of teclistamab to daratumumab-based induction regimens before stem cell transplant will be presented. These combinations are hoped to increase long-term disease-free survival of newly diagnosed myeloma patients.

• Phase 2 Study of Teclistamab-Based Induction Regimens in Patients with Transplant-Eligible (TE) Newly Diagnosed Multiple Myeloma (NDMM): Results from the GMMG-HD10/DSMM-XX (MajesTEC-5) Trial. Click here for details. Sunday, December 8, 2024: 9:30 AM (GMT-8)

The ASH congress will also see a range of oral and poster presentations exploring the role of CAR T-cell therapies and bispecific antibodies used as single agents or in combination with already approved treatments, and newly developed trispecific antibodies in the treatment of relapse refractory myeloma.

• Phase 2 Registrational Study of Anitocabtagene Autoleucel for the Treatment of Patients with Relapsed and/or Refractory Multiple Myeloma: Preliminary Results from the IMMagine-1 Trial. Click here for details. Monday, December 9, 2024: 5:30 PM (GMT-8)
• Efficacy of Elranatamab (ELRA) in Combination with Carfilzomib (CFZ) and Dexamethasone (DEX) in the Phase 1b MagnetisMM-20 Trial in Relapsed or Refractory Multiple Myeloma (RRMM). Click here for details. Monday, December 9, 2024: 5:15 PM (GMT-8)
• First Results of a Phase 1, First-in-Human, Dose Escalation Study of ISB 2001, a BCMAxCD38xCD3 Targeting Trispecific Antibody in Patients with Relapsed/Refractory Multiple Myeloma (RRMM). Click here for details. (GMT-8)

Results on other types of treatments will be also presented. If approved, these new agents and combinations will provide more treatment options for relapse refractory myeloma patients. In particular, the results of a study investigating the safety and efficacy of the Cereblon E3 ligase modulatory drug (CELMoD) mezigdomide (a new generation of IMID) in combination with dexamethasone and bortezomib or carfilzomib will be presented.

• Mezigdomide (MEZI) Plus Dexamethasone (DEX) and Bortezomib (BORT) or Carfilzomib (CFZ) in Patients (pts) with Relapsed/Refractory Multiple Myeloma (RRMM): Updated Results from the CC-92480-MM-002 Trial. Click here for details. Monday, December 9, 2024: 5:30 PM (GMT-8)

The safety and efficacy results of a new oral agent called inobrodib will also be presented. Inobrodib is a small molecule inhibitor drug which disrupts the growth of cancer cells. This treatment could provide patients with an oral-only treatment option at late treatment lines.

• Tolerability and Clinical Activity of Novel First-in-Class Oral Agent, Inobrodib (CCS1477), in Combination with Pomalidomide and Dexamethasone in Relapsed/Refractory Multiple Myeloma. Click here for details. Monday, December 9, 2024: 5:00 PM (GMT-8)

As treatment options can become burdensome for patients and leading to cumulative side effects, it is important to understand when it is safe to stop treatment to preserve quality of life and clinical outcomes. A study conducted in Germany investigated patients’ preferences on treatment free intervals to better tailor treatment plans to patients’ needs and desires.

• Balancing Treatment Intervals and Quality of Life in Multiple Myeloma Patients: Patient Perspectives and Recommendations. Click here for details. Saturday, December 7, 2024: 2:15 PM

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Chimeric antigen receptor T cell (CAR T-cell) therapy is a form of immunotherapy that is currently being investigated in clinical trials for the treatment of myeloma. Immunotherapy works by using your immune system to fight cancer. In CAR-T-cell treatment, a type of immune cell, known as T cells, are genetically programmed with a chimeric antigen receptor (CAR) protein that enables them to recognise and destroy cancerous myeloma cells in your body.

In clinical trials, researchers use specific inclusion and exclusion criteria during the enrolment process to determine the most appropriate and safe patient population to test new drugs. Your doctor will assess whether you meet these criteria and you must go through an initial comprehensive physical examination. Furthermore, regular and thorough check-ups will be carried out throughout the entire treatment process to monitor your health status. As CAR-T-cell treatment can take around six weeks to manufacture some patients may lose eligibility for enrolment in the clinical trial during this time. For example, during the manufacturing process patients may become weaker or their myeloma may progress and it is no longer safe for them to receive treatment with CAR-T-cells. Therefore, it is important to note that even if you are considered eligible and start the first phase of treatment in a CAR-T clinical trial, there is still a chance you can lose eligibility and may not receive the actual CAR-T-cell infusion.

Some common requirements for inclusion in a CAR T-cell clinical trial:

• You must be able to sign an informed consent form (in your native language) and agree to undergo all the required test procedures (such as blood tests, bone marrow biopsies, imaging, etc).
• As CAR-T-cell treatments are mostly being tested in patients who are relapsed/refractory (meaning disease that is worsening or no longer responds to treatment), you must have a documented diagnosis of myeloma with measurable disease (through blood or urine tests, imaging, or biopsy).
• Usually, an Eastern Cooperative Oncology Group (ECOG) score of fewer than 2 points is required. This score measures your overall fitness level by assessing how independently (or not) you can complete your daily activities such as bathing, cooking, etc. Patients with a higher ECOG score are considered less fit for treatment with CAR-T-cells.
• On average, you should have received at least 3 (range 2-4) previous lines of therapy (including proteasome inhibitors and immune modulators) and your myeloma should have worsened after or during your last treatment.
• You must have good functioning organs such as your kidney, liver, and heart. Organ function will likely be measured to determine your eligibility and how safe it is for you to participate in a CAR-T-cell clinical trial.
• Your neutrophil count (a type of immune cell) and platelet counts (a type of cell your body uses to stop bleeding) may also be taken into consideration.
• Also, often your life expectancy must be estimated to be greater than 3 months.

Some common reasons why you would not be able to participate in a CAR-T-cell clinical trial:

• You have an active hepatitis B virus (HBV) infection; hepatitis C virus (HCV) infection; HIV infection; syphilis infection; or an active, uncontrolled viral, bacterial, or fungal infection.
• You have an uncontrolled heart or vascular disease (e.g., frequent heart-related chest pain, uncontrolled high blood pressure, stroke, or heart attack, etc within 6 months of screening for enrolment into the clinical trial).
• You suffer from an uncontrolled liver, kidney, or metabolic disease.
• You have an autoimmune disease that requires treatment with drugs that suppress your immune system.
• You have an uncontrolled medical or psychiatric disorder that would influence the outcome of CAR-T-cell treatment.
• You are pregnant or breastfeeding.
• You have a history of a disease related to your nervous system causing frequent seizures, brain damage, dementia, or Parkinson’s disease.
• You have another cancer or have myeloma disease outside of your bone marrow (also known as extramedullary disease), although this may vary.

Please note, this is not a comprehensive list, and criteria for inclusion or exclusion in CAR-T-cell clinical trials may vary. This list is based on research carried out by MPE, during which protocols of 15 CAR-T-cell clinical trials were reviewed on www.clinicaltrials.gov. We advise that you consult your physician for further information or advice on your eligibility for a CAR-T-cell clinical trial.

For more information about myeloma, CAR T-cells and other treatments for myeloma check out the CARAMBA CAR-T clinical trial publication and ensure you follow MPE on social media: Facebook, Twitter, YouTube and LinkedIn. 

The post The Reality of CAR T-cell Therapy: Am I Eligible? appeared first on Myeloma Patients Europe.

Every myeloma patient has a story to tell. And every story captures a very personal experience of our incurable blood cancer.

Living with myeloma is more than navigating the physical challenges of illness and treatment. It is also about finding a path through mental health issues: toxic thoughts, rollercoaster emotions and imperilled well-being.

Because myeloma remains incurable, ultimately the journey is about accepting that the end of one’s life may be near. In short, we confront the spectre of death.

Here is my story of living with myeloma.

I have always been a healthy, high-energy person. Well into my late 50s, I worked hard and played hard. I thought nothing of spending ten hours at the office, then, before going home, heading to the racquet club to play squash or go for an hour run in the park.

When I was diagnosed with myeloma, in October 2009, at 61, my initial thought was: I must be the healthiest person alive with cancer. Then came the realisation that I had just been handed a death sentence.

Perhaps unsurprisingly, the first question I asked the haematologist was: “How long do I have left to live?” She replied somewhat firmly: “Wrong question. A lot of progress is being made in the treatment of myeloma. With any luck, you will benefit”.

She was giving me a message of hope: Don’t despair. Don’t give up. And she was right. Over the past 15 years progress has been tremendous, and I have benefited hugely.

After learning about my cancer, I decided on my roadmap: First, I resolved to make my story one of living with cancer rather than dying from cancer. Second, myeloma was not going to change who I am, how I live, or what I do. I was determined to carry on living fully as always, accepting the changed circumstances while rising to the challenge of cancer and its treatment.

Determination would be my guiding light. My mantra: Never give up. Just live.

So, I began my myeloma journey inspired by these lines from the American poet, Mary Oliver:

Tell me, what is it you plan to do

With your one wild and precious life?

In late February 2010, four months after my diagnosis, I was putting the finishing touches on a hiking trip in the Sacred Forests of Japan when I received a call from my haematologist. She informed me that I needed an urgent stem cell transplant. The myeloma was out of control. Immediate treatment was absolutely necessary.

With a sigh of disappointment, I cancelled my Japanese trip and began my myeloma journey instead.Three years later, at the end of June 2013, aged 65, I retired from a career in higher education. My myeloma was still under control after the successful stem cell transplant in 2010. My end-of-career plan was to embark on a biking adventure somewhere in South-east Asia.

I have been an avid cyclist since my youth. With retirement, I finally had time on my hands. I decided to take eight weeks and cycle down the Mekong River through Thailand, Laos and Cambodia. A band of similarly aged friends were keen to share the adventure. In January and February 2014, we made it happen, riding 2500 km on touring bikes along the banks of the mighty Mekong River, taking small boats when the roads ran out.

The Mekong trip was the first of many long-distance cycling trips around Southeast Asia and across Europe after my myeloma journey began. In mid-2014 my myeloma progressed again, so I began a new treatment with the immunomodulatory drug, Revlimid. That did not stop me from cycling that summer from Basel (Switzerland) to Budapest (Hungary) – 1500 km – with my supply of drugs in tow.

In the winter of 2015, still on Revlimid, I cycled 2500 km in Indonesia: across East Java, around Bali and Lombok, then Flores. A doctor friend from the Mekong trip cycled the mountainous island of Flores with me. I had lost none of my determination to enjoy life, explore new places, meet new people, and just live. My myeloma remained in check.

Throughout 2016 I felt pretty good although I had become refractory to Revlimid. In the winter, with the same doctor friend, we cycled across Sumatra, an island of high mountains, active volcanoes, and teeming jungles. And in the summer, with still another doctor friend, I cycled from the Italian border in France to the Atlantic Coast. The takeaway here: Doctors enjoy adventures too.

By the autumn of 2016, my myeloma needed treatment again. So, in January 2017 I began a clinical trial to explore the impact of a multi-drug strategy on myeloma, a triplet drug combination: a proteasome inhibitor (carfilzomib), an anti-CD38 monoclonal anti-body (daratumamab), and a corticosteroid (dexamethasone).

Two months before the start of the trial, knowing that I would be side-lined for the winter of 2017 and probably beyond, I cycled from Singapore up the Malay Peninsula to Phuket in Thailand (1500 km,) a confirmation that I still had plenty of life in me. The clinical trial went well and in the summer of 2018, I was able to get away for a short cycling break while still on treatment. But when I returned from 2 weeks of cycling the Saint James pilgrimage path in France, the study doctor withdrew me from the clinical trial: the myeloma had progressed alarmingly. So, I underwent an immediate second stem cell transplant.

That procedure, my fourth line of treatment, went well and I began maintenance therapy with pomalidamid, another immunomodulatory drug. It worked for the next three years, until December 2021, which was a nice long period of response.

COVID-19 arrived in early 2020, so my wings were clipped once again, at least on a bike. Just before the lockdown, in late February 2020, my wife and I managed a 50^th wedding anniversary trip to South-east Asia, spending a few weeks in Laos, Singapore and Bali.

In November 2021 I caught a nasty cold after a vigorous workout in a poorly heated yoga studio. By early December I had developed acute pneumonia and required hospitalization in the Intensive Care Unit (ICU) of the hospital in Paris where I am treated for myeloma. Somewhere along the line, I also contracted sepsis. Neither of these is good news for a myeloma patient.

During the clinical trial of 2017-2018, I had read about CAR-T cell therapy and told the haematologist that I was keen to undergo the therapy if and when it became necessary. The comment did not fall on deaf ears.

In early January 2022 she asked if I was still keen on a CAR-T. The therapy was achieving amazing responses in clinical trials and increasingly seen as the Holy Grail by myeloma patients. I accepted the offer on the spot.

The CAR-T was my fifth line of myeloma treatment. At that time, in France, only 10 patients per month were being offered access to a CAR-T. That is a woefully low number for a country with over 5,400 new cases each year and a 30,000-strong patient community.

I was fortunate to be among the lucky few. Since then, the situation has brightened considerably. Today, in France, well over 500 patients have been treated with the one commercial CAR-T available. The number is rising steadily. The collection of my lymphocytes took place in mid-March 2022 followed by their re-engineering and expansion in the US-based manufacturing facility.  In mid-May I was hospitalised for the reinfusion of the BCMA targeting T-cells.

The week after the reinfusion was a rough time with various side effects and numerous blood transfusions for anaemia, thrombocytopenia and neutropenia, both during and after the procedure. To complicate matters, in late June I began struggling with severe gastro-intestinal issues. At first, the medical team was not alarmed, but in early July, I had difficulty keeping food down. After two weeks of this, I was quite weak and finally hospitalised.

As you probably know, CAR-T treated patients are particularly vulnerable to infections. I had caught the COVID-19 virus while out and about after my release from the hospital. By late July I was stabilised, but not before losing more weight. During the CAR-T hospitalisation in May I had lost 8 kg, but now with COVID-19 in July I lost another seven. In just three months I had lost 15 kg (over 30 lbs) for my 1m82 (six feet) frame. Physical exercise of any kind was out of reach. Even a stroll around the block was an ordeal.

For years I have exercised two hours a day, so you can imagine my state of mind. In the summer of 2022, for the first time since 2010, I began to wonder if I wasn’t approaching the end of my life. I am an optimist by nature, so when I began having such dark thoughts, I knew it was time to get a grip on things and work at regaining my mental stamina and physical strength.

Gradually I recovered enough energy to return to the yoga studio, to play a bit of tennis, and even to get back on my bike to move around Paris. A source of pride has always been to cycle to my hospital appointments, a 20 km (12 mi) roundtrip. I have done this since 2009 and still do so today, 15 years later.

In late 2022, my wife and I rekindled our love for travel with two weeks around Italy, followed by a week in Rome. In early 2023, we revisited our favorite spots in Laos, including a six-day cruise on the Mekong River. By mid-2023, we enjoyed a week in Venice and a two-week trip through Central Europe with our granddaughters.

My quality of life and well-being would not be what they are without the support of my family and many friends who have always encouraged me to keep going and live. Today, two years into my CAR-T journey, I am still in complete response. The only significant health challenge I face is the risk of infection. In the past two years I have been hospitalised twice for viral infections. This is common for myeloma patients treated with the new BCMA-targeting immunotherapies.

I continue to have travel projects, of course. They enable me to project into the future, to frame a long-term, hope-filled horizon. This coming September I will complete a project I began in the summer of 2021: Cycle the English pilgrimage path from Canterbury to Rome. Back then I completed the first 1000 km to Lausanne. This year I will ride the last 1000 km over the Alps, through Tuscany and Umbria, and on to Rome. As I am now a bit older, and a bit less strong, I will ride an e-bike for the first time.

To conclude my story, here is something I learned from my frequent travels in Bali. In the 1930s, traditional Balinese painting was in decline, threatened with fossilisation. A group of painters decided to create a movement to revive their art. They called themselves Pita Maha, meaning « great vitality, strong determination. Their movement laid the foundations for the renewal and survival of Balinese painting.

Their mantra inspires me today, strengthening my resolve to live on.

I have added an element of my own: « unwavering resilience.

Great vitality, strong determination, unwavering resilience: these are just three of my responses to living with myeloma.

William Kenneth Casler

Paris France , June 2024

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This follows an earlier positive recommendation from the EMA – Committee for Medicinal Product for Human Use (CHMP), after which the European Commission had 60 days to ratify.

The Commission´s decision is based on the results of the Phase III clinical trial data from CARTITUDE-4 which looked at cilta-cel in patients who had one to three prior lines of therapy and were no longer responding to lenalidomide (i.e. lenalidomide refractory). The trial compared cilta-cel to a physician’s choice of either pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd) until disease progression. Patients in the cilta-cel arm also received PVd and DPd bridging therapy, prior to their single infusion of cilta-cel.

Cilta-cel was initially approved by the European Commission for myeloma patients who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti‑CD38 antibody and whose disease has worsened since the last treatment. The new European Commission approval means that cilta-cel will be licenced for use in earlier stages of myeloma (after at least one prior treatment). However, for patients to receive the treatment it usually requires a funding decision of national health authorities. MPE will continue to engage with members, industry and other stakeholders to understand access to cilta-cel in Europe.

MPE interviewed Dr. Hermann Einsele, Director of the Department of Internal Medicine II at the Würzburg University Hospital, Germany, at the European Hematology Association annual congress 2023 about the CARTITUDE-4 study. You can watch the video interview here.

For further information on cilta-cel, you can read the MPE ciltacabtagene autoleucel factsheet here.

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