General MM

Clinical Advances in Myeloma 2018 | An overview

The MM Hub were delighted to attend Clinical Advances in Myeloma 2018 on 31 January 2018, at the Hallam Conference Centre, London, UK. This was a small conference with approximately 40 attendees, plus several company representatives, and gave us an opportunity to chat informally with local clinicians. The day began with a welcome and introduction by Rakesh Popat from University College London Hospitals. The talks were then divided into several sessions covering Multidisciplinary Perspectives on Myeloma Management, Current and Emerging Treatment Regimens as well as Practical Management of Multiple Myeloma (MM), an interactive discussion session, and finally a session on Improving Patient Outcomes. Despite a focus on UK-centered treatment and care, much of the content and discussions will have wider relevance for the MM community. Some of the slides from the presentations can be viewed here, and highlights of the day are summarized below.

Multidisciplinary Perspectives on Myeloma Management

The first talk was delivered by Guy Pratt from the Institute of Immunology and Immunotherapy at the University of Birmingham, UK. Dr. Pratt talked through the various imaging methodologies and warned that the UK is falling behind with a lack of availability for whole body MRI, which has become the gold standard assessment procedure. This was followed by a detailed overview of the many genetic markers that have been linked to MM, and their clinical relevance presented by Martin Kaiser from the Institute of Cancer Research and the Royal Marsden Hospital, London. Dr. Kaiser concluded with a recommendation for how to apply treatment stratification decision making in 2018 with the agents and methods currently available. This session was concluded with a talk from Susanne Selvadurai from the Royal National Orthopaedic Hospital who talked about the management of spinal myeloma. Dr. Selvadurai used a series of case studies to illustrate the importance of being mindful of bone damage throughout the treatment journey, and how prophylactic measures, such as the use of bisphosphonates and TLSO braces, can have remarkable success. To read more details about these three talks, click here.

Current and Emerging Treatments

The second session of the morning addressed Current and Emerging Treatments and was kicked off with a talk by Jamie Cavenagh, from St Bartholomew’s Hospital, London, who spoke about Current Treatments for Newly Diagnosed Myeloma. He presented data from the many pivotal trials for frontline agents, but challenged the concept of continuous therapy until disease progression, and suggested that treatment-free intervals can be beneficial in limiting toxicity. Professor Cavenagh highlighted the importance of making the correct choice for the first agent in order to limit long-term toxicity, and also that management of patient wellbeing alongside therapy is paramount.

This was followed by a presentation from Rakesh Popat from the University College London Hospitals who spoke about emerging treatments for relapsed MM. Dr. Popat illustrated his talk with several cases studies in which multiple relapses were successfully salvaged with deep and durable responses at later stages of the disease and with suggestions for therapies at each relapse and a summary of the UK NHS treatment pathway for 2018 separated according to eligibility for transplant. One of the themes that emerged was the difficulty in choosing the correct agent at a given relapse stage in order to leave options for subsequent relapses, as many of the drug indications enable use at only a specified stage of relapse (eg. first, second or third). In addition, the indications often include specific requirements for prior treatments, which clearly presents a challenge to clinicians. Indeed, the biology of the disease is reflected in the fact that treatment of the first relapse usually drives a more prolonged response. In line with Professor Cavanagh’s talk, there was an emphasis on limiting toxicity to avoid a vicious cycle of decline, with patients requesting therapies that ‘don’t make them feel worse than they already do’. How novel therapies such as antibodies fit into the MM landscape was also touched on, as well as upcoming trials with novel CAR T-cell therapies, in particular, the AUTO2 phase I/II trial being conducted in the UK with APRIL CAR T-cells. To read more about this two talks, click here.

Improving Outcomes of Stem Cell Therapy was the topic addressed by Gordon Cook from St. James’ University Hospital, Leeds, who discussed the role that autologous stem cell transplant (ASCT) holds in the era of novel agents. The take-home message was that the need for transplant remains a cyclical question, but that currently ASCT remains safe and effective in driving depth of MRD negativity, and is therefore likely to continue to be used alongside novel agents. However, it was emphasized that careful patient selection remains critical. In addition, the choice of induction therapy can impact depth of response and it will be interesting to see how novel agents play into this stage of therapy, with the possibility of transplant being pushed to second-line therapy. Post-transplant salvage maintenance and salvage transplant were also discussed.

Chris Parrish, from The Leeds Teaching Hospitals Foundation Trust, spoke about Emerging Immunotherapy Treatments and how these fit into current clinical practice. He began with a historical introduction to immunotherapy and heralded the arrival of the first monoclonal to treat MM – daratumumab. Dr. Parrish then introduced the concept of checkpoint blockade (PD-1 inhibition) and outlined the promising data in both frontline and relapsed settings for these molecules. Despite some setbacks in clinical trials with different combos (there are 5 different checkpoint blocking antibodies in clinical trials for MM), at least two of these are expected to re-open. The success of the GSK2857916 antibody was also touched on, as were CAR T-cells. In particular, Dr. Parrish highlighted the bb2121 trial data presented at ASH – see previous MM Hub article. He also discussed so-called off-the-shelf CAR T-cells and the Bi-specific T-cell Engagers (BITEs), which combine T-cell specific target such as CD3 with a tumor-specific target in order to bring T cells in direct contact with myeloma cells. Finally, Dr. Parrish explained the concept of oncolytic viruses, which preferentially lyse cancer cells and at the same time prime anti-tumor immune responses, and briefly outlined the MUK eleven trial in Relapsed and Refractory (RR) MM. The challenge in this field is understanding how and when to combine agents and managing the toxicities of cytokine release syndrome (CRS), infusion reactions and tumor flare, with cost ultimately being the largest limiting factor. To read more about these two talks, click here.

Practical Management and Interactive Sessions

Ceri Bygrave from the University Hospital of Wales, UK, spoke about putting the most recent NICE guidelines into practice. A detailed overview of the diagnosis and staging workup was outlined, followed by recommended frontline regimens: bortezomib-based (VTD or Vel-Dex) for transplant eligible, and MPT/CTD as an option for non-transplant eligible patients; VCD if contraindication to thalidomide (NTE). The value of frailty assessments for patient selection was emphasized, along with the value of treatment dosing in the frail or elderly. The use of tandem transplant was advocated as an option for high-risk healthy patients, following impressive data in Michele Cavos’ study (#ASH17 abstract 401, PFS single vs tandem = 64% vs 73%). The study used VCD upfront, autografts, and lenalidomide maintenance. The guidelines for RRMM patients is more complicated, with comorbidities and residual toxicity from prior treatments a big consideration. Despite a wide array of agents now on offer, the many caveats for their use need to be taken into account when designing treatment algorithms for the ongoing treatment journey. The MM Hub has interviewed Dr. Bygrave to follow up on this, so look out for this article coming soon.

The next session was an interactive discussion attempting to answer the question: Should we be treating smoldering myeloma earlier? Charlotte Pawlyn, Kwee Yong, and Jamie Cavenagh all presented data and case studies to fuel the discussion. Look out for more detailed coverage of this debate on a forthcoming piece on the MM Hub.

Jennifer Heaney from the University of Birmingham presented a practical comparison of two methodologies to measure serum free light chains and used a series of case studies to illustrate the various pros and cons. A summary can be read here.

Ashutosh Wechalekar from the Amyloidosis Centre at University College London presented an interactive case study of myeloma and the identification AL amyloidosis as a complication. The problem of organ responses in AL amyloidosis was outlined, with improving responses remaining a challenge. However, earlier treatment leads to an improved outcome, but identifying early symptoms and a fast disease pace can make this difficult. In addition, the techniques used to assess the presence of amyloid deposits need careful consideration, such as widening the antibody panel and being mindful that congo red can lead to both false positives and negatives, therefore histology of target organs is necessary to confirm a diagnosis.

Improving Patient Outcomes

Simon Ridley from Myeloma UK spoke about assessing patient values and preferences, in terms of defining patient centricity and ways in which to balance treatment benefits against risks. He explained how patient preferences stretch beyond the outcomes assessed in clinical trials and presented data from two ‘Patient Preference’ studies. The first study asked the questions: What treatment attributes do patients value? What benefit/risk trade-offs characterize patients’ decision-making around treatment options, including not to treat? and What influences the way patients assess benefits and risk? The second study sought to understand what myeloma patients think about the positive and negative effects associated with myeloma treatment.  However, both Health Technology Assessments (HTAs) and the National Institute for Health and Care Excellence (NICE) remain unsure how to incorporate such preferences into their decision making. However, this is a developing field with future collaboration and partnerships likely to help such information make a meaningful impact.

The final talk of the day was given by Dunnya De-Silva from University College London and focused on the topic of developing patient-centered models of care. The aims of the study were to engage with patients in order to design a system of care that allows patients to self-manage their condition using a method of their choice, and also providing patients with the necessary knowledge, skills, and confidence to do this. However, the initial qualitative research revealed mixed feelings amongst patients with a general lack of desire to monitor their own bloods and varied ability to recognize symptoms of a relapse. In addition, there were varied beliefs on physical and psychological well-being and diverse disease features and toxicity from prior treatments. Interestingly, the desire for independence differed according to the stage of the disease, with patients in a progression-free state more keen for independence, whereas those experiencing relapse possibly felt more vulnerable and preferred face to face consultations. Therefore, the aims were modified to provide individualized holistic management of remission, as well as actively promoting survivorship. The MM Hub will be following up on this with an interview.

Conclusion

Some of the key discussion points centered around how success with novel therapies means that MM patients are living much longer, but that this in turn presents the challenge of dealing with multiple relapses and managing associated comorbidities. This was particularly relevant for the discussion related to Susanne Selvadurai’s talk, which means that most patients will be referred to orthopedics during the course of their treatment journey, and that doctors in hematology/oncology and orthopedics need to collaborate with their decision making. Another discussion point was the restrictions placed on the choice of therapy at a given stage of relapse, which makes the decision making algorithms extremely complex. Additionally, there are blocks on certain therapies as an inevitable consequence of limited funding, particularly in the UK NHS.

The ‘one size doesn’t fit all’ message is a recurrent theme for MM, and was illustrated through a number of case studies throughout the day, at all stages of the disease. The use of case studies to balance data from recommended guidelines and decision algorithms will undoubtedly help steer a personalized approach in MM and highlights the importance of smaller conferences, where time permits a greater exchange of ‘real life’ data outside of the reportage of large clinical trials. This article will be updated to include links to follow-on articles (on the MM Hub) as they become available.

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