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.

How I treat extramedullary myeloma

“…35,36 Retrospective studies highlight an extremely poor prognosis for CNS EMM with a median overall survival of ,6 months. [35][36][37][38][39] Any neurologic symptom presented by an MM patient should raise the possibility of the presence of CNS EMM. However, alternative diagnoses should be considered (eg, hypercalcemia, hyperviscosity, spinal cord compression, CNS infection, and peripheral neuropathy).…”

Successful Intrathecal Chemotherapy Combined with Radiotherapy Followed by Pomalidomide and Low-Dose Dexamethasone Maintenance Therapy for a Primary Plasma Cell Leukemia Patient

“…2 months). 15 By multivariable analysis, extramedullary lesions, prior to treatment with novel drugs, and high LDH levels at myeloma diagnosis were statistically independent predictors of post CNS-MM survival. These findings corroborate our observations that our patient with CNS relapse of PPCL had an extremely short-term outcome.…”

“…It has been reported that 19% of post CNS-MM patients met the criteria for PPCL. 15 Furthermore, some of these PPCL patients developed isolated CNS relapse during systemic remission after auto-SCT. 8,9,15 In a prospective study by Royer et al, 2 PPCL patients experienced neuromeningeal relapse after autologous- and allo-SCT, respectively, and both patients soon died despite intrathecal chemotherapy.…”

“…15 Furthermore, some of these PPCL patients developed isolated CNS relapse during systemic remission after auto-SCT. 8,9,15 In a prospective study by Royer et al, 2 PPCL patients experienced neuromeningeal relapse after autologous- and allo-SCT, respectively, and both patients soon died despite intrathecal chemotherapy. 7 In the present case, although VGPR was maintained by RVD induction therapy followed by allo-SCT, isolated CNS relapse occurred within 1 year.…”

“…15 Meanwhile, IMiDs such as thalidomide and pomalidomide effectively penetrate the BBB. 15-17 Of note, BBB penetration of lenalidomide was 11% in a rhesus monkey model, whereas that of thalidomide was 42%.…”