Philip McCarthy, MD, Director of the Blood and Marrow Transplant Center at Roswell Park Comprehensive Cancer Center in Buffalo, NY, comments on the U.S. Food and Drug Administration (FDA)'s approval of REVLIMID (lenalidomide) maintenance therapy, after autologous stem cell transplant, for multiple myeloma. Dr. McCarthy, who authored cancer research that led to the FDA's approval, also shares benefits of lenalidomide maintenance therapy for multiple myeloma patients.

Samir N. Parekh, MD, Icahn School of Medicine at Mount Sinai, New York City, NY, outlines the current staging system for multiple myeloma and suggests how it may be improved. The recently Revised International Staging System (R-ISS) including simple biochemical measures of tumor burden and select high-risk cytogenetic features is most commonly used in the clinic. Nevertheless, a recent study using a multi-omics approach integrating whole genome sequencing, whole exome sequencing, and RNA sequencing demonstrated that incorporating 1q amplification in the current staging system allowed to further discriminate between patients. Prof. Parekh expects that the R-ISS will be updated to include a larger number of genetic alterations. This interview took place during the 36th Society for Immunotherapy of Cancer (SITC) Annual Meeting in Washington, D.C.

Rakesh Popat, BSc, MBBS, MRCP, FRCPath, PhD, University College London Hospitals, London, UK, outlines treatment options for patients with multiple myeloma with 17p deletion, highlighting key clinical trials. Numerous studies have demonstrated that this patient population has a poorer prognosis compared to other patients with multiple myeloma. The HOVON-65/GMMG-HD4 study (EudraCT 2004-000944-26) and the TOURMALINE-MM1 study (NCT01564537) have reported a survival benefit for patients with del(17p) receiving continuous bortezomib treatment and ixazomib in combination with lenalidomide and dexamethasone respectively, suggesting the combination of a proteasome inhibitor with an immunomodulatory agent as a promising treatment option for these patients. This interview took place at the 62nd Annual Scientific Meeting of the British Society for Haematology (BSH) 2022, in Manchester, UK.

What is the current treatment landscape for plasma cell leukemia and extramedullary disease in multiple myeloma (MM)? We spoke to Niels van de Donk, MD, PhD, of VU University Medical Center, Amsterdam, Netherlands, about this at the European School of Haematology (ESH) International Conference on MM 2018, held in Mandelieu, France.

Graham Jackson, MBBS, FRCP, FRCPath, MD, Newcastle upon Tyne Hospitals NHS Trust, Newcastle, UK, discusses maintenance therapy when treating multiple myeloma. Previously, steroids, chemotherapy and thalidomide have been unsuccessful. Prof. Jackson mentions that the ideal maintenance therapy should have no impact on subsequent therapy and prolong progression-free survival. There is a lot of data supporting the use of lenalidomide as maintenance therapy in myeloma, such as the CALGB 100104 trial (NCT00114101) and the IFM trial (NCT03606577). Proteasome inhibitors also show potential for maintenance therapy. Bortezomib has been investigated in the HOVON-65/GMMG-HD4 trial (2004-000944-26) and shows powerful activity. For high-risk patients, a proteasome inhibitor plus an IMiD could be potential maintenance treatment. Additionally, Prof. Jackson discusses daratumumab maintenance therapy in transplant eligible participants with previously untreated multiple myeloma. This interview took place during the Controversies in Multiple Myeloma (COMy) 2020 Virtual World Congress.

Multiple myeloma is also a cancer of the bone marrow. Myeloma starts in the bone marrow from a cell called as plasma cell. It is a cancer of the plasma cell. In Multiple myeloma, which is basically a cancer of the elderly, the plasma cells release toxins, which can affect the kidney, which can affect the bone marrow and the bone. So the patient can present with varied symptoms. The most common symptom being bony pains, low backache, rib pains, which are not relieved by rest. It can present with renal failure or just anaemia or symptoms due to high calcium in the blood. It is very important to identify and recognize symptoms and evaluate properly, because the earlier we start treatment in myeloma, the better are the results. Myeloma is not a curable disease, but can be controlled in majority of the patients. There are newer drugs available in the treatment of myeloma, which make the chances of response to the treatment very high. Myeloma is managed by chemotherapy drugs, which are given in the form of injections and tablets and you can prolong the lifespan of a patient with myeloma easily upto 5 to 6 years.

Gordon Cook, MB ChB, PhD, FRCP(Glas), FRCPath, Leeds Teaching Hospitals NHS Trust, Leeds, UK, discusses the importance of identifying patients with multiple myeloma with high-risk disease, based on clinical as well genomic features. Despite previous exclusion from clinical trials, recent assessments of T-cell redirecting therapies have included patients with clinical high-risk disease and such patients receiving lenalidomide, dexamethasone, and eculizumab have shown similar responses to patients without high-risk markers. This interview took place during the 7th World Congress on Controversies in Multiple Myeloma (COMy), 2021.

En sık izlenen malign plazma hücre tümörüdür. Ortalama 65 yaşında izlenir. Neoplastik plazma hücrelerinin monoklonal proliferasyonu ve anormal aşırı immünoglobulin sentezi ile karakterizedir.
Tipik olarak kemik ağrıları, litik kemik lezyonları, hiperkalsemi, sedimantasyon yüksekliği, renal yetmezlik ve hümoral immünite yetmezliği birarada izlenir.
Protein elektroforezinde M spike varlığı anormal aşırı immünoglobulin sentezini gösterir ve tanısaldır. Ayrıca tanıda kemik iliği aspirasyonunda %10’un üzerinde plazma hücre
varlığı çok değerlidir.
Kemik rezorpsiyonu sonucu patolojik fraktürler ve kronik kemik ağrıları izlenir. En sık vertebra, kosta, kafatası, pelvis, köprücük ve skapula kemiklerini tutar.
• Bu kemiklerde zımba deliği tarzında multifokal litik lezyonlar izlenir.
• Kemik yıkımına hiperkalsemi eşlik eder. Hiperkalsemiye ait klinik bulgular gözlenmeye başlanır. (Konfüzyon, letarji, halsizlik, poliüri ve kabızlık)
• Hümoral immün yetmezliğe sekonder bakteri enfeksiyonları eşlik eder. En sık ölüm nedeni enfeksiyonlardır. İkinci ölüm nedeni renal yetmezliktir.
Renal yetmezliğin bu olgularda temel nedeni idrarla atılan immünoglobulinlerin böbrek tübüllerinde neden olduğu
toksisitedir. (Bence Jones Proteinürisi) Ayrıca hiperkalsemi de renal yetmezliğe katkı sağlar.
• Tipik olarak AL tip amiloidoz izlenir ve amiloid proteinleri böbrekte birikerek böbrek yetmezliğine katkı sağlarlar.
• Serumda yüksek seviyede olan M proteinler eritrositlerde karakteristik Rülo formasyonuna neden olur. (Lupus ve HIV enfeksiyonunda da izlenir.)
Ayrıca multiple myelom patogenezinden sorumlu temel sitokin IL-6’dır. IL-6 plazma hücrelerinin proliferasyonunu
sağlayan temel sitokindir. Tümör hücrelerinden sentezlenen sitokinler özellikle MIP1-alfa RANKL uyarısıyla osteoklastları aktive eder.
• Yüksek IL-6 serum seviyeleri kötü prognoz ile ilişkilidir.
Mikroskopik incelemede sitoplazmalarında immunoglobülin ürünleri alev şeklini almışsa Flame hücreleri, üzüm salkımına benzer benekli görünümdeyse Mott hücreleri adını alırlar. İmmunoglobülin inklüzyonları stoplazmadaysa Russel body nükleustaysa Dutcher body adını alırlar.