title: Lack of survival improvement with novel anti-myeloma agents for patients with multiple myeloma and central nervous system involvement: the Greek Myeloma Study Group experience.
abstract: Involvement of the central nervous system (CNS) is a rare complication of multiple myeloma (MM). Herein, we have described the incidence, characteristics, prognostic factors for post CNS-MM survival, and outcome of CNS-MM and explored the efficacy of novel agents (NA) (thalidomide, bortezomib, lenalidomide) in this setting. Between 2000 and 2013, 31 (0.9 %) out of 3408 newly diagnosed symptomatic MM patients, consecutively diagnosed and treated during the same period in 12 Greek centers, developed CNS-MM (M/F 15/16, median age 59 years, range 20-96 years; newly diagnosed/relapsed-refractory 2/29; median time to CNS-MM diagnosis 29 months). Clinical and laboratory characteristics were retrospectively recorded. Twenty-six percent of patients had circulating plasma cells (PCs) or plasma cell leukemia (PCL) at CNS-MM and 39 % had skull-derived plasmacytomas, suggesting hematological and contiguous spread. Treatment for CNS-MM was offered in 29/31 patients and 11/29 responded (NA 18/29, additional radiotherapy 9/28, intrathecal chemotherapy 13/29). The median post CNS-MM survival was 3 months (95 % CI 1.9-4.1) and did not differ between patients treated with NA and/or radiotherapy vs. others. In the multivariate analysis, prior treatment of MM with NA, extramedullary disease (EMD) during MM course (i.e., plasmacytomas, circulating PCs, or documented PCL) and abnormally high LDH at MM diagnosis were independent prognostic factors, whereas treatment of CNS-MM with NA did not predict for post CNS-MM survival. Despite the relatively limited number of patients due to the rarity of CNS-MM, our results suggest that NA do not seem to improve post CNS-MM survival. Patients with EMD display shortened post CNS-MM survival and should be followed thoroughly.
authors.affiliation: Greek Myeloma Study Group, Athens, Greece. eirinikatodritou@gmail.com.|Department of Hematology, Theagenio Cancer Hospital, Thessaloniki, Greece. eirinikatodritou@gmail.com.
authors.forename: Eirini
authors.initials: E
authors.lastname: Katodritou
authors.affiliation: Greek Myeloma Study Group, Athens, Greece.|Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece.
authors.forename: Evangelos
authors.initials: E
authors.lastname: Terpos
authors.affiliation: Greek Myeloma Study Group, Athens, Greece.|Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece.
authors.forename: Efstathios
authors.initials: E
authors.lastname: Kastritis
authors.affiliation: Greek Myeloma Study Group, Athens, Greece.|Department of Hematology and Bone Marrow Transplantation Unit, Evangelismos Hospital, Athens, Greece.
authors.forename: Sossana
authors.initials: S
authors.lastname: Delimpasis
authors.affiliation: Greek Myeloma Study Group, Athens, Greece.|Hematology Division, Department of Internal Medicine, University of Patras Medical School, Patras, Greece.
authors.forename: Argiris S
authors.initials: AS
authors.lastname: Symeonidis
authors.affiliation: Greek Myeloma Study Group, Athens, Greece.|Department of Hematology, Metaxa Cancer Hospital, Piraeus, Greece.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Repousis
authors.affiliation: Greek Myeloma Study Group, Athens, Greece.|First Propedeutic Department of Internal Medicine, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Kyrtsonis
authors.affiliation: Department of Hematology, 424 General Military Hospital, Thessaloniki, Greece.
authors.forename: Chrysa
authors.initials: C
authors.lastname: Vadikolia
authors.affiliation: Greek Myeloma Study Group, Athens, Greece.|Department of Hematology, Geniko Kratiko General Hospital, Athens, Greece.
authors.forename: Eurydiki
authors.initials: E
authors.lastname: Michalis
authors.affiliation: Department of Hematology, Theagenio Cancer Hospital, Thessaloniki, Greece.
authors.forename: Genovefa
authors.initials: G
authors.lastname: Polychronidou
authors.affiliation: Greek Myeloma Study Group, Athens, Greece.|Department of Hematology, General Hospital, Lefkosia, Cyprus.
authors.forename: Michael
authors.initials: M
authors.lastname: Michael
authors.affiliation: Department of Hematology, Theagenio Cancer Hospital, Thessaloniki, Greece.
authors.forename: Sofia
authors.initials: S
authors.lastname: Papadaki
authors.affiliation: Greek Myeloma Study Group, Athens, Greece.|Department of Hematology-Bone Marrow Transplantation Unit, George Papanicolaou Hospital, Thessaloniki, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Papathanasiou
authors.affiliation: Greek Myeloma Study Group, Athens, Greece.|Department of Hematology, Papageorgiou General Hospital, Thessaloniki, Greece.
authors.forename: Kyriaki
authors.initials: K
authors.lastname: Kokoviadou
authors.affiliation: Department of Hematology, Papageorgiou General Hospital, Thessaloniki, Greece.
authors.forename: Anna
authors.initials: A
authors.lastname: Kioumi
authors.affiliation: Greek Myeloma Study Group, Athens, Greece.
authors.forename: Eythimia
authors.initials: E
authors.lastname: Vlachaki
authors.affiliation: Department of Hematology, Theagenio Cancer Hospital, Thessaloniki, Greece.
authors.forename: Christina
authors.initials: C
authors.lastname: Hadjiaggelidou
authors.affiliation: Greek Myeloma Study Group, Athens, Greece.|Hematology Division, Department of Internal Medicine, University of Patras Medical School, Patras, Greece.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kouraklis
authors.affiliation: Department of Hematology, Metaxa Cancer Hospital, Piraeus, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Patsias
authors.affiliation: Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Gavriatopoulou
authors.affiliation: Greek Myeloma Study Group, Athens, Greece.|Department of Hematology, Metaxa Cancer Hospital, Piraeus, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Kotsopoulou
authors.affiliation: Department of Hematology, Theagenio Cancer Hospital, Thessaloniki, Greece.
authors.forename: Evgenia
authors.initials: E
authors.lastname: Verrou
authors.affiliation: Department of Hematology, Theagenio Cancer Hospital, Thessaloniki, Greece.
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Gastari
authors.affiliation: Greek Myeloma Study Group, Athens, Greece.|Department of Hematology, 251 General Air Force Hospital, Athens, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Christoulas
authors.affiliation: Department of Hematology, Theagenio Cancer Hospital, Thessaloniki, Greece.
authors.forename: Evlambia
authors.initials: E
authors.lastname: Giannopoulou
authors.affiliation: Greek Myeloma Study Group, Athens, Greece.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Pouli
authors.affiliation: Department of Hematology, Theagenio Cancer Hospital, Thessaloniki, Greece.
authors.forename: Pavlina
authors.initials: P
authors.lastname: Konstantinidou
authors.affiliation: Greek Myeloma Study Group, Athens, Greece.|Department of Hematology-Bone Marrow Transplantation Unit, George Papanicolaou Hospital, Thessaloniki, Greece.
authors.forename: Achilles
authors.initials: A
authors.lastname: Anagnostopoulos
authors.affiliation: Greek Myeloma Study Group, Athens, Greece.|Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece.
authors.forename: Meletios-Athanasios
authors.initials: MA
authors.lastname: Dimopoulos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016543:Central Nervous System Neoplasms / Q000401:mortality* / Q000628:therapy*; D018572:Disease-Free Survival; D005260:Female; D006115:Greece / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000401:mortality* / Q000628:therapy*; D015996:Survival Rate
keywords: CNS myeloma; Novel agents; Prognostic factors; Survival