BACKGROUND: Invasion of CNS in MM is an extremely rare occurrence that is associated with advanced disease with poor prognosis. PATIENTS AND METHODS: Our MM database identified 35 CNS MM cases presenting between January 1996 and March 2012. Descriptive analyses were performed on available data on patient characteristics, disease course, and outcomes. RESULTS: The mean age at diagnosis was 55.4 years; 23.5% (n = 8) patients had elevated levels of beta-2-microglobulin > 5.5 mg/L; 68.6% (n = 24) of patients had elevated lactate dehydrogenase (LDH) levels (≥ 2 times upper limit of normal); and 14% (n = 5) of patients had secondary plasma cell leukemia. Magnetic resonance imaging (MRI), which was performed in 34 patients, showed diffuse or localized leptomeningeal disease in 20 patients (58.8%). Monoclonal malignant plasma cells were found by CSF analysis in all 35 patients. In total, 31 patients received chemotherapy, including intrathecal chemotherapy as a part of their treatment, with a median survival of 4 months after CNS MM diagnosis. DISCUSSION: In our experience, CNS MM is an aggressive terminal disease feature associated with high beta-2-microglobulin level, high LDH level, and secondary plasma cell leukemia. This study highlights an unmet need in this subset of patients with high-risk, relapsed or refractory MM. CONCLUSION: Achieving adequate CSF penetration while limiting the off-target effects needs to be considered in MM-specific novel drug development.
BACKGROUND: Invasion of CNS in MM is an extremely rare occurrence that is associated with advanced disease with poor prognosis. PATIENTS AND METHODS: Our MM database identified 35 CNS MM cases presenting between January 1996 and March 2012. Descriptive analyses were performed on available data on patient characteristics, disease course, and outcomes. RESULTS: The mean age at diagnosis was 55.4 years; 23.5% (n = 8) patients had elevated levels of beta-2-microglobulin > 5.5 mg/L; 68.6% (n = 24) of patients had elevated lactate dehydrogenase (LDH) levels (≥ 2 times upper limit of normal); and 14% (n = 5) of patients had secondary plasma cell leukemia. Magnetic resonance imaging (MRI), which was performed in 34 patients, showed diffuse or localized leptomeningeal disease in 20 patients (58.8%). Monoclonal malignant plasma cells were found by CSF analysis in all 35 patients. In total, 31 patients received chemotherapy, including intrathecal chemotherapy as a part of their treatment, with a median survival of 4 months after CNS MM diagnosis. DISCUSSION: In our experience, CNS MM is an aggressive terminal disease feature associated with high beta-2-microglobulin level, high LDH level, and secondary plasma cell leukemia. This study highlights an unmet need in this subset of patients with high-risk, relapsed or refractory MM. CONCLUSION: Achieving adequate CSF penetration while limiting the off-target effects needs to be considered in MM-specific novel drug development.
Authors: C M Comerford; R Morrell; D Johnson; M Javadpour; A Beausang; J Cryan; P Murphy; J Quinn Journal: Ir J Med Sci Date: 2017-10-18 Impact factor: 1.568
Authors: Artur Jurczyszyn; Norbert Grzasko; Alessandro Gozzetti; Jacek Czepiel; Alfonso Cerase; Vania Hungria; Edvan Crusoe; Ana Luiza Miranda Silva Dias; Ravi Vij; Mark A Fiala; Jo Caers; Leo Rasche; Ajay K Nooka; Sagar Lonial; David H Vesole; Sandhya Philip; Shane Gangatharan; Agnieszka Druzd-Sitek; Jan Walewski; Alessandro Corso; Federica Cocito; Marie-Christine M Vekemans; Erden Atilla; Meral Beksac; Xavier Leleu; Julio Davila; Ashraf Badros; Ekta Aneja; Niels Abildgaard; Efstathios Kastritis; Dorotea Fantl; Natalia Schutz; Tomas Pika; Aleksandra Butrym; Magdalena Olszewska-Szopa; Lidia Usnarska-Zubkiewicz; Saad Z Usmani; Hareth Nahi; Chor S Chim; Chaim Shustik; Krzysztof Madry; Suzanne Lentzsch; Alina Swiderska; Grzegorz Helbig; Renata Guzicka-Kazimierczak; Nikoletta Lendvai; Anders Waage; Kristian T Andersen; Hirokazu Murakami; Sonja Zweegman; Jorge J Castillo Journal: Am J Hematol Date: 2016-04-24 Impact factor: 10.047
Authors: Muhammad Bilal Abid; Sanjay De Mel; Muhammad Abbas Abid; Kong Bing Tan; Wee Joo Chng Journal: Cancer Biol Ther Date: 2016-04-22 Impact factor: 4.742
Authors: Gergely Varga; Gábor Mikala; László Gopcsa; Zoltán Csukly; Sarolta Kollai; György Balázs; Tímár Botond; Nikolett Wohner; Laura Horváth; Gergely Szombath; Péter Farkas; Tamás Masszi Journal: J Oncol Date: 2018-04-23 Impact factor: 4.375
Authors: Philip A Egan; Patrick T Elder; W Ian Deighan; Sheila J M O'Connor; H Denis Alexander Journal: Haematologica Date: 2020-05-15 Impact factor: 9.941