scholarly journals EPID-28. THE IMPACT OF RITUXIMAB COMBINATION CHEMOTHERAPY ON THE CLINICAL OUTCOMES OF PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA (PCNSL): AN UPDATED META-ANALYSIS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii84-ii84
Author(s):  
Philip Haddad ◽  
Dalia Hammoud ◽  
Kevin Gallagher
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Clinical Outcomes ◽  
Combination Chemotherapy ◽  
Comparative Studies ◽  
Meta Analysis ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Phase Ii Trials ◽  
The Impact

Abstract BACKGROUND PCNSL is a rare diffuse large B-cell lymphoma (DLBCL) confined to the central nervous system accounting for approximately 2–5% of all primary brain tumors. Although there is no standard combination of chemotherapy, high-dose methotrexate is considered the backbone of all PCNSL chemotherapy regimens. Rituximab, an anti-CD20 antibody, has been a standard component of DLBCL combinations since it improves progression-free (PFS) and overall survival (OS). However, the role of Rituximab in the treatment of PCNSL has been controversial with contradictory RESULTS: A small meta-analysis conducted in 2019 found no associated survival advantage for Rituximab when added to chemotherapy. However, this meta-analysis was small and included only 2 studies. The purpose of this updated meta-analysis is to evaluate in a more comprehensive way the impact of Rituximab combination chemotherapy on the clinical outcomes of patients with PCNSL incorporating all available comparative studies. METHODS A review of the medical literature was conducted using online databases. Inclusion criteria consisted of PCNSL diagnosis, English language, and studies reporting OS and PFS with hazard ratios (HR) or Kaplan-Meier curves that compared similar regimens with and without Rituximab. A meta-analysis using an inverse variance method with a random-effects model was conducted. RESULTS Four comparative studies with a total of 467 patients were included in this meta-analysis. Two of these studies were retrospective comparative studies and two were randomized phase II trials. When added to chemotherapy, Rituximab was found to significantly improve the OS and PFS (HROS 0.75, 95%CI: 0.59–0.96, p=0.02; HRPFS 0.67, 95%CI: 0.53–0.85, p=0.001) with a heterogeneity estimate, I2=0%. CONCLUSIONS This is the first meta-analysis to show that adding Rituximab to chemotherapy is associated with OS and PFS in patients with PCNSL. In the absence of randomized clinical trials, this meta-analysis represents the most compelling data supporting the routine use of Rituximab combinations in PCNSL.

scholarly journals The Impact of Rituximab on the Clinical Outcomes of Primary Central Nervous System Lymphoma (PCNSL) When Added to Combination Chemotherapy: A Comprehensive Meta-Analysis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 11-12
Author(s):  
Philip A Haddad ◽  
Dalia Hammoud ◽  
Kevin M. Gallagher
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Clinical Outcomes ◽  
Comparative Studies ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Phase Ii Trials ◽  
The Impact

Introduction: PCNSL is a rare diffuse large B-cell lymphoma (DLBCL) confined to the central nervous system accounting for approximately 2-5% of all primary brain tumors. Although there is no standard combination of chemotherapy, high-dose methotrexate is considered the backbone of all PCNSL chemotherapy regimens. Rituximab, an anti-CD20 antibody, has been a standard component of non-CNS DLBCL combinations since it improves progression-free (PFS) and overall survival (OS). However, the role of Rituximab in the treatment of PCNSL has been controversial with contradictory results. A meta-analysis conducted in 2019 found no associated survival advantage for Rituximab when added to chemotherapy. However, this meta-analysis was small and included only 2 studies. The purpose of this meta-analysis is to evaluate in a more comprehensive way the impact of Rituximab-based chemotherapy combinations on the clinical outcomes of patients with PCNSL incorporating all available comparative studies. Methods: A review of the medical literature was conducted using online databases. Inclusion criteria consisted of PCNSL diagnosis, English language, and studies reporting OS and PFS with hazard ratios (HR) or Kaplan-Meier curves that compared similar regimens with and without Rituximab. A meta-analysis using an inverse variance method with a random-effects model was conducted. Results: Four comparative studies with a total of 467 patients were included in this meta-analysis. Two of these studies were retrospective comparative studies and two were randomized phase II trials. When added to chemotherapy, Rituximab was found to significantly improve the OS and PFS (HROS 0.75, 95%CI: 0.59-0.96, p=0.02; HRPFS 0.67, 95%CI: 0.53-0.85, p=0.001) with a heterogeneity estimate, I2=0%. Conclusions: This is the first meta-analysis to show that adding Rituximab to chemotherapy is associated with OS and PFS in patients with PCNSL. In the absence of randomized clinical trials, this meta-analysis represents the most compelling data supporting the routine use of Rituximab combinations in PCNSL. Disclosures No relevant conflicts of interest to declare.

NCOG-04. THE IMPACT OF PROPHYLAXIS CHEMOTHERAPY ON CENTRAL NERVOUS SYSTEM (CNS) RELAPSES OF HIGH RISK DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL): A NETWORK META-ANALYSIS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi152-vi153
Author(s):  
Philip Haddad ◽  
Dalia Hammoud ◽  
Kevin Gallagher
Keyword(s):  
High Risk ◽  
Comparative Studies ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
B Cell Lymphoma ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Recurrence Rates ◽  
Cns Prophylaxis ◽  
The Impact

Abstract BACKGROUND CNS relapses with DLBCL tend to be uncommon. The risk increases with certain DLBCL types and certain identified risk features. There is no consensus regarding the optimal approach to CNS prophylaxis for high-risk DLBCL patients. While some favor prophylaxis with high-dose systemic therapy or intrathecal chemotherapy (IT), some experts advocate combining both approaches. In the absence of randomized trials, the role of chemotherapy prophylaxis remains controversial in DLBCL with contradictory comparative studies. The purpose of this meta-analysis is to evaluate the impact of CNS prophylaxis approaches on the clinical outcomes of high-risk DLBCL. METHODS A review of the medical literature was conducted using online databases. Inclusion criteria consisted of DLBCL diagnosis, English language, IT or high-dose systemic prophylactic chemotherapy, and comparative studies reporting CNS recurrence rates. A frequentist and Bayesian network meta-analysis were conducted using the netmeta package and random-effects model. RESULTS Twenty-one comparative studies with a total of 11,507 patients were included and analyzed. The relative risk (RR) of CNS recurrence was not statistically different between IT prophylaxis, high-dose chemotherapy, and no prophylaxis. However, the combination of IT prophylaxis and high-dose chemotherapy was found to be significantly associated with a reduced RR of CNS recurrence when compared to IT prophylaxis (RR 0.28, 95%CI 0.13-0.58), high-dose chemotherapy (RR 0.34, 95%CI 0.14-0.80), and no prophylaxis (RR 0.41, 95%CI 0.19-0.87). CONCLUSIONS This network meta-analysis is the first to compare the different CNS prophylactic approaches. It indicates that IT prophylaxis and high-dose chemotherapy each were not better than no prophylaxis. However, the combination of IT prophylaxis with high-dose chemotherapy was significantly superior to each approach alone as well as no prophylaxis. In the absence of randomized clinical trials, this network meta-analysis represents the most compelling data supporting the use of CNS prophylaxis in patients with high-risk DLBCL.

scholarly journals Effective Central Nervous System (CNS) Prophylaxis Chemotherapy Approach in High Risk Diffuse Large B-Cell Lymphoma (DLBCL): A Network Meta-Analysis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1461-1461
Author(s):  
Philip A Haddad ◽  
Dalia Hammoud ◽  
Kevin M. Gallagher
Keyword(s):  
High Risk ◽  
Comparative Studies ◽  
Randomized Clinical Trials ◽  
Conflicts Of Interest ◽  
Meta Analysis ◽  
B Cell Lymphoma ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Cns Prophylaxis ◽  
The Impact

Abstract Introduction: CNS relapses with DLBCL tend to be uncommon. The risk increases with certain DLBCL types and certain risk features. There is no consensus regarding the optimal approach to CNS prophylaxis for high-risk DLBCL patients. While some favor prophylaxis with high-dose systemic therapy or intrathecal chemotherapy (IT), some experts advocate combining both approaches. In the absence of randomized trials, the role of CNS chemotherapy prophylaxis remains controversial in DLBCL with contradictory comparative studies. The purpose of this meta-analysis is to evaluate the impact of CNS prophylaxis approaches on the clinical outcomes of high-risk DLBCL. Methods: A review of the medical literature was conducted using online databases. Inclusion criteria consisted of DLBCL diagnosis, English language, IT or high-dose systemic prophylactic chemotherapy, and comparative studies reporting CNS recurrence rates. A frequentists and Bayesian network meta-analyses were conducted using the netmeta package and random-effects model. Results: Twenty-one comparative studies with a total of 11,507 patients were included and analyzed. The relative risk (RR) of CNS recurrence was not statistically different between IT prophylaxis, high-dose chemotherapy, and no prophylaxis. However, the combination of IT prophylaxis and high-dose chemotherapy was found to be significantly associated with a reduced RR of CNS recurrence when compared to IT prophylaxis (RR=0.28, 95%CI 0.13-0.58), high-dose chemotherapy (RR=0.34, 95%CI 0.14-0.80), and no prophylaxis (RR=0.41, 95%CI 0.19-0.87). Conclusions: This network meta-analysis is the first to compare the different CNS prophylactic approaches. It indicates that IT prophylaxis and high-dose chemotherapy each were not better than no prophylaxis. However, the combination of IT prophylaxis with high-dose chemotherapy was significantly superior to each approach alone as well as no prophylaxis. In the absence of randomized clinical trials, this network meta-analysis represents the most compelling data supporting the use of CNS prophylaxis in patients with high-risk DLBCL. Disclosures No relevant conflicts of interest to declare.

scholarly journals RADT-37. THE IMPACT OF POSTOPERATIVE RADIATION THERAPY (PORT) AND EXTENT OF SURGERY ON CLINICAL OUTCOMES OF ATYPICAL MENINGIOMA (AM): A META-ANALYSIS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii189-ii189
Author(s):  
Philip Haddad ◽  
Furqan Akhtar ◽  
Kevin Gallagher
Keyword(s):  
Clinical Outcomes ◽  
Comparative Studies ◽  
English Language ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Subtotal Resection ◽  
Recurrence Rates ◽  
Postoperative Radiation Therapy ◽  
Extent Of Surgery ◽  
The Impact

Abstract BACKGROUND Although meningiomas are among the most prevalent types of brain tumors, AMs account for around 4% of all meningiomas. AMs tend to be more aggressive with relatively higher rates of recurrence and mortality. Gross total resection (GTR) has been the standard of care when possible. However, GTR itself is not always enough to prevent the recurrence of AMs. The role of PORT remains controversial in AM as the comparative studies to support its use have provided conflicting RESULTS: The purpose of this meta-analysis is to evaluate the impact of PORT on clinical outcomes according to the extent of resection in AMs. METHODS A review of the medical literature was conducted using online databases. Inclusion criteria consisted of AM diagnosis, English language, Simpson graded resections, and comparative studies reporting recurrence rates (RcR), Progression-Free Survival (PFS), and Overall Survival (OS) with hazard ratios (HR) or Kaplan-Meier curves. A meta-analysis was conducted using an inverse variance method with a random-effects model. RESULTS Twenty-two comparative studies with a total of 5,129 patients were included and analyzed. When GTR was attained, PORT was associated with improved RcR (HR =0.72, 95%CI:0.59-0.86) and PFS (HR=0.77, 95%CI:0.65-0.90), but not OS (HR=0.93, 95%CI:0.83-1.04). When subtotal resection (STR) was attained, PORT was associated with improved PFS (HR=0.35, 95%CI:0.26-0.48) as well as OS (HR=0.70, 95%CI:0.54-0.89). The extent of surgery also impacted AM outcomes as GTR demonstrated superior PFS (HR=0.45, 95%CI:0.31-0.65) and OS (HR=0.30, 95%CI:0.13-0.72). CONCLUSIONS This is the first meta-analysis to show that PORT is associated with PFS benefit in AMs with GTR and STR. Moreover, PORT significantly improved OS of AMs that underwent STR but had no impact on OS when GTR was achieved. In the absence of randomized clinical trials, this meta-analysis represents the most compelling data supporting the use of PORT in this patient population.

scholarly journals Treatment of secondary central nervous system involvement in systemic aggressive B cell lymphoma using R-MIADD chemotherapy: a single-center study

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yuchen Wu ◽  
Xuefei Sun ◽  
Xueyan Bai ◽  
Jun Qian ◽  
Hong Zhu ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Central Nervous System Involvement ◽  
Central Nervous System Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Cns Involvement ◽  
The Central Nervous System ◽  
Secondary Central Nervous System

Abstract Background Secondary central nervous system lymphoma (SCNSL) is defined as lymphoma involvement within the central nervous system (CNS) that originated elsewhere, or a CNS relapse of systemic lymphoma. Prognosis of SCNSL is poor and the most appropriate treatment is still undetermined. Methods We conducted a retrospective study to assess the feasibility of an R-MIADD (rituximab, high-dose methotrexate, ifosfamide, cytarabine, liposomal formulation of doxorubicin, and dexamethasone) regimen for SCNSL patients. Results Nineteen patients with newly diagnosed CNS lesions were selected, with a median age of 58 (range 20 to 72) years. Out of 19 patients, 11 (57.9%) achieved complete remission (CR) and 2 (10.5%) achieved partial remission (PR); the overall response rate was 68.4%. The median progression-free survival after CNS involvement was 28.0 months (95% confidence interval 11.0–44.9), and the median overall survival after CNS involvement was 34.5 months. Treatment-related death occurred in one patient (5.3%). Conclusions These single-centered data underscore the feasibility of an R-MIADD regimen as the induction therapy of SCNSL, further investigation is warranted.

scholarly journals Challenges in the Treatment of Newly Diagnosed and Recurrent Primary Central Nervous System Lymphoma

2020 ◽  
Vol 18 (11) ◽  
pp. 1571-1578
Author(s):  
Matthias Holdhoff ◽  
Maciej M. Mrugala ◽  
Christian Grommes ◽  
Thomas J. Kaley ◽  
Lode J. Swinnen ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
B Cell ◽  
Central Nervous System Lymphoma ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Newly Diagnosed ◽  
Phase Ii Trials ◽  
Whole Brain Radiation ◽  
The Central Nervous System

Primary central nervous system lymphomas (PCNSLs) are rare cancers of the central nervous system (CNS) and are predominantly diffuse large B-cell lymphomas of the activated B-cell (ABC) subtype. They typically present in the sixth and seventh decade of life, with the highest incidence among patients aged >75 years. Although many different regimens have demonstrated efficacy in newly diagnosed and relapsed or refractory PCNSL, there have been few randomized prospective trials, and most recommendations and treatment decisions are based on single-arm phase II trials or even retrospective studies. High-dose methotrexate (HD-MTX; 3–8 g/m2) is the backbone of preferred standard induction regimens. Various effective regimens with different toxicity profiles can be considered that combine other chemotherapies and/or rituximab with HD-MTX, but there is currently no consensus for a single preferred regimen. There is controversy about the role of various consolidation therapies for patients who respond to HD-MTX–based induction therapy. For patients with relapsed or refractory PCNSL who previously experienced response to HD-MTX, repeat treatment with HD-MTX–based therapy can be considered depending on the timing of recurrence. Other more novel and less toxic regimens have been developed that show efficacy in recurrent disease, including ibrutinib, or lenalidomide ± rituximab. There is uniform agreement to delay or avoid whole-brain radiation therapy due to concerns for significant neurotoxicity if a reasonable systemic treatment option exists. This article aims to provide a clinically practical approach to PCNSL, including special considerations for older patients and those with impaired renal function. The benefits and risks of HD-MTX or high-dose chemotherapy with autologous stem cell transplantation versus other, better tolerated strategies are also discussed. In all settings, the preferred treatment is always enrollment in a clinical trial if one is available.

Primary and Secondary Central Nervous System Lymphoma: Outcomes from Houston Methodist Cancer Center

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 16-17
Author(s):  
Cesar Gentille Sanchez ◽  
Ethan Burns ◽  
Ibrahim Muhsen ◽  
Humaira Sarfraz ◽  
Carlo Guerrero ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Central Nervous System Lymphoma ◽  
B Cell Lymphoma ◽  
Cancer Center ◽  
Cns Lymphoma ◽  
High Dose ◽  
Cell Transplant ◽  
Female Ratio ◽  
Multiagent Chemotherapy

Introduction Primary Central Nervous System Lymphoma (PCNSL) is a rare form of extra-nodal non-Hodgkin Lymphoma (NHL), with diffuse large B-cell Lymphoma (DLBCL) reported in 90% of cases. Secondary CNS lymphoma (SCNSL) may occur as an isolated recurrence of previously diagnosed NHL or occur simultaneously as a manifestation of systemic disease. Comparative data on survival in treated PCNSL and SCNSL in the real-world setting is lacking. We present a retrospective analysis of outcomes in PCNSL and SCNSL patients treated at the Houston Methodist Cancer Center. Methods We retrospectively identified patients with a diagnosis of PCNSL or SCNSL from 2015 to 2020. Data collected included age, race, sex, diagnosis (PCNSL, SCNSL), histology and immunohistochemistry, treatment type (chemotherapy, radiation), transplant rates as well as outcomes (alive/dead). Responses were classified as complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). Survival was analyzed using Kaplan-Meier methodology, and log-rank tests were used to compare survival distributions. P < 0.05 was considered statistically significant. Results There were 50 patients with CNS lymphoma identified between 2015 and 2020; 68% were PCNSL. Out of 43 with available pathology, 2 patients were T-cell lymphomas and 41 DLBCL. Out of the DLBCL cases, 95% of cases expressed CD20 while close to 60% were positive for MUM1, bcl-2 and bcl-6. Less than 15% of cases were positive for CD10. CD30 was positive in 17% of cases. Cerebral hemispheres (76%) was the most common organ involved, followed by ocular (8%), intraventricular space (6%) and cerebellum (6%). Median age at diagnosis was 67 years; male to female ratio was 1.27. Caucasian (62%) and Hispanic (24%) were most common ethnicities. Epstein-Barr Virus was positive in 14% of patients (5 in PCNSL and 2 in SCNSL). One patient with SCNSL had human immunodeficiency virus. The median follow-up time was 9.1 months. Multiagent chemotherapy including high dose methotrexate (MTX), cytarabine and rituximab was given to 48% of the patients while 32% received high dose MTX alone plus rituximab. From the latter group, five out of sixteen patients received temozolomide. Other regimens were used in 6% of the cases. Median dose of MTX in a multiagent chemotherapy regimen was 2.5gr/m2 and 2.25gr/m2 when used alone or with temozolomide. Median number of cycles given was 3. Radiation therapy alone was given to 8% of cases. Three patients did not receive treatment. For patients with PCNSL, overall response rate (ORR) was 82.8% (CR 65.5%, PR 13.8%, SD 3.4%). ORRs were similar between multiagent chemotherapy and methotrexate alone (+/- temozolomide) with 86.7% and 83.3% respectively. ORR for SCNSL was 57.1% (CR 35.7%, PR 21.4%); only 1 patient was treated with MTX alone. Further lines of therapy were required in 9.3% of patients. Consolidation with whole brain radiation was given in 22% of the cases (29.4% for PCNSL and 6.3% for SCNSL). Autologous stem cell transplant was performed in 10% of the patients (2 PCNSL, 3 SCNSL). Overall survival for patients with PCNSL was 74.8 months and 10.1 months for SCNSL (p=0.0444) (Figure 1). Survival was not significant between patients receiving multiagent chemotherapy and MTX alone or in combination with temozolomide (3-year OS 57.3% vs 73.4%, p= 0.5652) (Figure 2). Conclusion Most patients diagnosed with PCNSL are non-germinal center DLBCL. Median MTX dose was lower than 3gr/m2 with excellent ORR of over 80% in PCNSL. Response rates were lower in SCNSL and in general, patients with PCNSL had better outcomes. Survival did not differ significantly between regimens, suggesting that a lower intensity therapy may perform similarly to multiagent chemotherapy. These results need to be confirmed by prospective studies. Disclosures No relevant conflicts of interest to declare.

scholarly journals Primary Central Nervous System Lymphoma in an Immunocompetent Patient Presenting as Multiple Cerebellar Lesions: A Case Report and Review of Literature

2019 ◽  
Vol 7 ◽  
pp. 232470961989354
Author(s):  
Gliceida M. Galarza Fortuna ◽  
Kathrin Dvir ◽  
Christopher Febres-Aldana ◽  
Michael Schwartz ◽  
Ana Maria Medina
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Lesion ◽  
Central Nervous System Lymphoma ◽  
B Cell Lymphoma ◽  
Immunocompetent Patient ◽  
Cns Lymphoma ◽  
High Dose ◽  
Older Woman ◽  
Non Hodgkin Lymphoma

Primary central nervous system (CNS) lymphoma (PCNSL) is an uncommon extranodal non-Hodgkin lymphoma often presenting as a single brain lesion within the CNS. On histopathological evaluation of PCNSL a positive CD10, which is frequently observed in systemic diffuse large B-cell lymphoma, is present in approximately 10% of PCNSL. We describe a case of CD10-positive PCNSL presenting with multiple posterior fossa enhancing lesions in an immunocompetent older woman with a history of breast cancer successfully treated by the RTOG 0227 protocol consisting of pre-irradiation chemotherapy with high-dose methotrexate, rituximab, and temozolomide for 6 cycles, followed by low-dose whole-brain radiation and post-irradiation temozolomide.

Central Nervous System and Intracranial Myeloma: a Retrospective Italian Multicenter Study.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1882-1882
Author(s):  
Alessandro Gozzetti ◽  
Stefania Oliva ◽  
Fabiana Gentilini ◽  
Elena Marchini ◽  
Maria Teresa Petrucci ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Liposomal Doxorubicin ◽  
Biological Data ◽  
High Dose ◽  
Poor Prognostic Factor ◽  
Β2 Microglobulin ◽  
Presenting Symptoms ◽  
The Impact

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.

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