Articles

Practical recommendations for the management of late relapsed and refractory multiple myeloma in 2024

BJH - volume 15, issue 6, october 2024

N. Kint MD, PhD, M.C. Vekemans MD, N. Meuleman MD, PhD, J. Caers MD, PhD, C. Doyen MD, J. Depaus MD, R. Callens MD, G. Claes MD, C. Jacquy MD, PhD, A. Kentos MD, PhD, H. Maes MD, F. Offner MD, PhD, A. Salembier MD, R. Schots MD, PhD, K. Theunissen MD, I. Vande Broek MD, PhD, A. Van De Velde MD, PhD, K.L. Wu MD, PhD, M. Delforge MD, PhD

SUMMARY

Despite significant advances in therapeutic modalities, the treatment of relapsed and refractory multiple myeloma (RRMM) is still challenging. In this publication, we aim to provide an update on therapeutic modalities for RRMM in Belgium. First, novel combinations of well-established therapeutic agents will be discussed. Second, T-cell redirection therapies will be addressed. These include bispecific antibodies, both anti-BCMA x CD3 and anti-GPRC5D x CD3, as well as chimeric antigen receptor (CAR) T cell therapy. Third, we discuss novel modalities such as antibody-drug conjugates, selinexor, venetoclax, melflufen and CELMoDs. Finally, a general flowchart regarding overall treatment sequencing will be proposed, providing an integrated treatment recommendation from frontline to relapse.

(BELG J HEMATOL 2024;15(6):225–32)

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Multiple myeloma: Practical recommendations for the management of early relapses 2024

BJH - volume 15, issue 4, june 2024

M.C. Vekemans MD, N. Kint MD, PhD, G. Claes MD, C. Doyen MD, V. Galle MD, C. Jacquy MD, PhD, H. Maes MD, N. Meuleman MD, PhD, O. Rizzo MD, A. Salembier MD, H. Schots MD, PhD, G. Verstraete MD, M. Delforge MD, PhD

SUMMARY

Despite the increasing availability of more effective treatments for newly diagnosed multiple myeloma (NDMM) patients that provide longer disease-free periods, almost all patients will experience a relapse. Managing relapse after regimens that have included a proteasome inhibitor (PI), an immunomodulatory drug (IMID), and often an anti-CD38 monoclonal antibody can be challenging, but therapeutic options have greatly increased over the past decades. This review covers the current second-line therapeutic options and provides updated information on novel agents for the treatment of early relapses in MM patients.

(BELG J HEMATOL 2024;15(4):158–64)

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Multiple myeloma: Practical recommendations for front-line therapy 2024

BJH - volume 15, issue 3, may 2024

M.C. Vekemans MD, N. Meuleman MD, PhD, N. Kint MD, PhD, G. Claes MD, C. Doyen MD, V. Galle MD, C. Jacquy MD, PhD, H. Maes MD, O. Rizzo MD, A. Salembier MD, H. Schots MD, PhD, G. Verstraete MD, M. Delforge MD, PhD

SUMMARY

With the introduction of immunomodulatory drugs, proteasome inhibitors and anti-CD38 monoclonal antibodies, major improvements have been achieved in the treatment and outcome of multiple myeloma. Different treatment combinations are now in use and quadruplets have been investigated with success. This rapidly changing therapeutic landscape urges for an update on practical guidelines. Based on an extensive review of the recent literature, we propose recommendations on myeloma management, to be used by haematologists as a reference for daily practice.

(BELG J HEMATOL 2024;15(3):103–16)

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Rethinking the reimbursement of innovative medicines in oncology: Looking beyond overall survival

BJH - volume 14, issue 6, october 2023

M. Piccart MD, PhD, J. Vansteenkiste MD, PhD, H. Prenen MD, PhD, F. Duhoux MD, PhD, A. Janssens MD, PhD, M. Delforge MD, PhD, A. Awada MD, PhD, P. Neven MD, PhD, A. Sibille MD, B. Neyns MD, PhD

SUMMARY

The oncological treatment landscape is evolving at a very rapid pace with a continuous stream of novel treatment options. To fully leverage these therapeutic advances in clinical practice it is important to facilitate a rapid access to innovative anticancer drugs for patients. Specifically for Belgium, the delay from EMA approval to reimbursement for anticancer drugs is very long, with an average of almost 600 days, and a substantial proportion of innovative drugs never make it to the patient. The stringent focus of the Belgian Commission for Reimbursement of Medicines (CRM) on overall survival (OS) data in reimbursement decisions is believed to be an important contributor to this situation. However, the ever-increasing pace at which new anticancer therapies are being developed in combination with an earlier detection of cancer will make it increasingly difficult to present mature OS data at the time of regulatory approval in the years to come. As such, there is an urgent need for a debate with the regulators to consider more readily available endpoints in their reimbursement assessments. In fact, when a strong treatment effect is seen on an intermediate endpoint such as disease-free or progression-free survival, a benefit in OS is quite likely. As such, our reimbursement system needs to be adapted to better align with the scientific progress in oncology. In this, a temporary reimbursement decision based on intermediate endpoints could give Belgian patients earlier access to promising lifesaving medicines. In this, we as oncologists, including specialists in haematology, respiratory oncology, and gastrointestinal cancer, strongly encourage the CRM to use the grading provided by the ESMO magnitude of clinical benefit scale to evaluate the clinical added value of future cancer treatments. This will not only facilitate a faster patient access to innovative therapies, but will also help policy-makers in advancing ‘accountability for reasonableness’ in their resource allocation deliberations.

(BELG J HEMATOL 2023;14(6):245–9)

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Highlights in multiple myeloma

BJH - volume 14, issue 5, september 2023

M. Delforge MD, PhD

SUMMARY

The treatment of relapsed and refractory multiple myeloma (MM) currently undergoes a new (r-)evolution. Real-world data like those from the LocoMMotion study have confirmed the grim outcome of MM patients who have received ≥3 treatment lines or who are refractory to the current backbone treatments that include a proteasome inhibitor, an immunomodulatory drug (IMiD) and an anti-CD38 monoclonal antibody.1 The median progression-free survival (PFS) and overall survival (OS) of this heavily pre-treated patient population is around four months and their overall survival barely exceeds one year. Until recently, the treatment options for this patient population were very limited and consisted mostly of retreatment with the drugs that had already been given in earlier treatment lines.2 Currently, the recently introduced T-cell redirecting therapies are completely reshaping the treatment paradigm of relapsed and refractory MM (triple class exposed and mostly triple class refractory). These therapies include CAR-T cells, bispecific antibodies and to a lesser extent antibody drug conjugates. Whereas B-Cell Maturation Antigen (or BCMA) is the most frequently targeted surface antigen, other targets include G-Protein Coupled Receptor family C group 5 member D (or GPRCD). It was therefore no surprise that the oral sessions on treatment of MM were nearly completely dedicated to T-cell redirecting therapies. In the following article, the most recent insights presented at the EHA congress in Frankfurt are discussed.

(BELG J HEMATOL 2023;14(5):216–8)

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Plasma cell leukaemia with an indolent clinical presentation

BJH - volume 13, issue 7, november 2022

N. Kint MD, PhD, M. Delforge MD, PhD

SUMMARY

Plasma cell leukaemia (PCL) is a rare and aggressive plasma cell malignancy and is generally considered to be the final stage of multiple myeloma (MM). Although treatment modalities for MM have significantly evolved in the past decades, PCL unfortunately still retains an overall dismal prognosis, with most patients presenting with a highly symptomatic and aggressive disease course. We present a case of a transplant-ineligible patient diagnosed with a primary PCL who had an indolent presentation and achieved a durable complete remission after treatment via bortezomib-lenalidomide-dexamethasone (VRD). The present case illustrates the clinical heterogeneity of plasma cell disorders, and highlights the necessity of careful cytomorphological and flow cytometric analysis of aberrant lymphoid cells, even in the absence of stigmata of MM.

(BELG J HEMATOL 2022;13(7):277–80)

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Guidelines of the Belgian Hematology Society for imaging in multiple myeloma

BJH - volume 12, issue 8, december 2021

N. Meuleman MD, PhD, J. Caers MD, PhD, K. Fostier MD, P. Vlummens MD, S. Pans MD, L. Goethals MD, PhD, J. Alexiou MD, M. Cliquennois MD, C. Doyen MD, A. de Weweire MD, R. Schots MD, PhD, M. Delforge MD, PhD, M.C. Vekemans MD

SUMMARY

Despite major improvements in the diagnosis and treatment of multiple myeloma (MM), bone damage remains a major feature of this disease. With the development of new diagnostic tools, conventional skeletal studies have been progressively replaced by novel imaging techniques. Today, imaging plays a crucial role in defining symptomatic multiple myeloma, measurement of the extent of skeletal involvement and assessing therapeutic response including minimal residual disease (MRD). Based on an extensive review of the recent literature, we propose an array of Belgian recommendations for myeloma imaging to be used as a reference by haematologists in their daily practice.

(BELG J HEMATOL 2021;12(8):338–43)

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