Central Nervous System and Intracranial Myeloma: a Retrospective Italian Multicenter Study.
Authors: Gozzetti Alessandro , Oliva Stefania , Gentilini Fabiana , Marchini Elena , Petrucci Maria Teresa , Patriarca Francesca , Petrucci Alessandro , Giaccone Luisa , Zamagni Elena , Genuardi Mariella , Cavo Michele , Palumbo Antonio , Rossi Davide , Offidani Massimo , Cerase Alfonso , De Paoli Lorenzo , Floridia Michele , Mele Giuseppe , Galli Monica , Beretta Salvatore , Di Raimondo Francesco , Vallone Roberto , Lauria Francesco 
Published: October 2019

Abstract
Abstract 1882
Poster Board I-905

Introduction.
Intracranial involvement (IC) in multiple myeloma (MM) is extremely rare, most frequently resulting from osseous lesions in the cranial vault and skull base. Central nervous system (CNS) MM is even rarer (arising in less than 1% of the patients) consisting in intraparenchymal localizations, cerebral plasmacytomas or CNS myelomatosis. Patients described in the literature are few and treatments are variegate: systemic chemotherapy, (CHT), intrathecal therapy, (IT), radiotherapy, (RT) with results being discouraging with median survivals of 1 month or less. The impact of new drugs (thalidomide, bortezomib, lenalidomide) on CNS and IC MM has not been reported.

Patients and Methods.
We retrospectively collected clinical and biological data of patients presenting with a CNS or IC MM irrespective of disease status (diagnosis, response, relapse) by sending a questionnaire to the GIMEMA (Gruppo Italiano Malattie Ematologiche dell'Adulto) centers. Twelve centers answered.

Results.
Clinical characteristics. A total of 32 patients (M:F=18:14) were registered. All patients had an IC or CNS MM observed in the period between 2004–2009. Ten patients presented a CNS involvement, while 22 had an IC involvement. 9/32 patients had a CNS /IC involvement at diagnosis (4/5); 23/32 patients has a CNS/IC involvement after a median of 16 months (range 1–104) from MM diagnosis. Median age was 63 years (range 44–83) with no difference in both groups; monoclonal protein was IgG 18 (k16, λ2), IgA 6 (k4, λ2), BJ 6 (k3, λ3), non secretory 2. One patient had a solitary primitive IC plasmacytoma, 1 patient had an extramedullary localization in the lung. β2-microglobulin was available in 23 patients with a median value of 4 (range 1.1–17,5): ≤3.5 in 9 patients; >3.5<5.5 in 8 patients; >5.5 in 6 patients. FISH on bone marrow plasma cells was available in 11/32 patients: 60% of the patients showed genomic abnormalities, the more frequent being in order del 13q, t(11;14), del 17p. The most frequent presenting symptoms were in order headache (30%), confusion (27%), visual disturbances (25%), extremities weakness (21%), cranial nerve palsies (21%), paraesthesias (12%), vertigo (5%), convulsions (4%). Magnetic resonance imaging (MRI) of the brain was the preferred radiological imaging in 23/32 patients; computed tomography (CT) was used in 9/32 patients. Cerebrospinal fluid (CSF) involvement was demonstrated in 5/10 CNS MM. Cytogenetic analysis of cerebrospinal fluid was available in two patients who showed a complex karyotype.

Treatment.
CHT only was administered to 21 patients, CHT+RT to 5 patients, CHT+RT+IT to 3 patients, RT only to 1 , CHT +IT to 1, RT+IT to 1. Bortezomib was used in 15 patients, Thalidomide in 9, Lenalidomide in 3, MP in 7 , VAD in 3, PAD (with liposomal doxorubicin) in 2, cyclophosphamide in 3, other treatments in 3, and 8 patients received an high dose treatment + stem cells transplant (SCT) (5 Autologous/ 3 Allogeneic). 18/32 patients had a response after treatment defined as at least a reduction of 50% of the mass and /or M component (13 CR+VGPR) ; 17 patients had symptoms disappearance. PFS was at a median of 5 months (range 1–36). Median OS for CNS MM was 5 months (range 1–23), OS for IC MM was 9 months (range 1–42). 5/10 patients with CNS MM died at a median of 2 months (1–6); while 13/22 IC MM died at median of 8 months (1–46). 14/32 patients are alive at the present time (5 CNS, 9 IC). Interestingly, of 5 CNS MM patients alive 1 had AutoSCT , 4 received Bortezomib (1 combined with MP, 2 with liposomal doxorubicin, 1 with thalidomide); while of the 9 IC MM alive 3 received Bortezomib, 3 Auto SCT, 1 thalidomide, 1 lenalidomide, 1 cyclophosphamide. β2-microglobulin > 5.5 was a poor prognostic factor, as well as age >65 years.

Conclusions.
High dose therapies followed by autologous SCT seem to be the preferable therapy for eligible young patients. Novel drugs such as bortezomib, thalidomide, lenalidomide seem to increase the quality of responses and to prolong survival respect to what reported in the literature. Largest prospective studies are needed to confirm these findings.

Disclosures:
Petrucci: celgene: Honoraria; Jansenn-cilag: Honoraria. Palumbo:CELGENE: Honoraria.