scholarly journals Assessing Steroid Toxicity in the Elderly with Multiple Myeloma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5557-5557
Author(s):  
Vidhya Nair ◽  
Hadi Mohammed ◽  
Sharmeen Mahmood ◽  
Pushpinderdeep Singh Kahlon ◽  
Philip Kuriakose
Keyword(s):  
Central Nervous System ◽  
Multiple Myeloma ◽  
Nervous System ◽  
Adverse Effects ◽  
Elderly Patients ◽  
Dose Reduction ◽  
The Elderly ◽  
High Dose ◽  
Full Dose ◽  
Starting Dose

Background The mainstay of treatment for Multiple Myeloma (MM) includes various combinations of chemotherapy, which generally includes high dose steroids. The median age at diagnosis for MM is above 60 years. Patients above the age of 70 may not be considered for an auto peripheral blood transplant, resulting in being treated with chemotherapy alone. This often leads to a relatively long period of steroid exposure. Increasing age is a risk factor for decreased tolerance to steroids, and increased drug toxicity. As such, the steroid dose (usually Dexamethasone) is often considered for reduction in patients above a certain age. However, there are no clear guidelines regarding a standard dose to use in the elderly, nor is there uniformity among clinicians in the way doses are chosen. Purpose To assess a) the starting dose of Dexamethasone (dex) in the elderly, b) frequency of dose reduction of dexamethasone, c) adverse effects of dex treatment in the elderly with MM, and d) average time after dose reduction. Methods We performed a 10 year retrospective chart review on patients, age 70 or greater treated at Henry Ford Health System with a diagnosis of MM from 2000-2015. Patients were grouped by age 70-75 years, 76-80 years, and greater than 80 years based on when treatment was initiated. We investigated the starting treatment dose of dex, ranging from 1-20 mg weekly and 21-40 mg weekly. Secondly, we assessed for the occurrence of dose reduction; and, if present, the length of time to reducing the dose. Lastly, the types of adverse effects to dex leading to dose reduction were grouped by system, such as, central nervous system, musculoskeletal, endocrine, gastrointestinal and psychiatric. Data collected was categorical, thus, no statistical tests were performed as this was a descriptive study. Results A total of 150 patients were reviewed and 91 patients met the inclusion criteria. Of these patients, 8 (8.8%) were started at doses between 1-20 mg and majority (62.5%) were ages 70-75, thus, there was no relation between lower starting dose and age. Of the 91 patients, 24 (26.4%) had a dose reduction and 11 (12.1%) had both chemotherapy and dex discontinued prior to therapy completion. Majority (87.5%) of patients that had a dose reduction were initially started at 40 mg. The reasons for dose reduction included adverse effects grouped by musculoskeletal (29.17%), psychiatric (16.67%), endocrine (12.3%), central nervous system (4.17%), and gastrointestinal (4.17%). Of note, 8 patients (33.3%) had dose reductions as result of their clinical trial requirement. The average length of dex therapy before dose reduction was 17.2 months. Conclusion The majority of elderly patients (age 70 or above) with MM tolerated full doses of dex without adverse effects. Secondly, there was no relation between lower starting dose for dex and advanced age. However, since there were limited patients (n=8) who started at a low dose, other than those on clinical trials, we were not able to do a comparison of starting doses. But we were able to show that the majority of patients tolerated full dose, despite their age. The most frequent cause of steroid toxicity was musculoskeletal, such as leg swelling. On average, elderly patients were able to tolerate full dose of dex for over 1 year prior to requiring a dose reduction. Summary Our data demonstrates no correlation between advanced age in MM and lack of tolerability of high dose steroids. In conclusion, current findings do not justify reduced doses solely based on age alone. Future studies could include investigating statistical analysis on steroid exposure and survivorship. Disclosures Kuriakose: Alexion: Consultancy, Honoraria, Speakers Bureau; Bayer: Consultancy.

scholarly journals Primary Central Nervous System Lymphoma in Elderly Patients: Management and Perspectives

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3479
Author(s):  
Andrea Morales-Martinez ◽  
Fernando Lozano-Sanchez ◽  
Alberto Duran-Peña ◽  
Khe Hoang-Xuan ◽  
Caroline Houillier
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Elderly Patients ◽  
Treatment Strategies ◽  
Central Nervous System Lymphoma ◽  
High Dose Chemotherapy ◽  
Current Treatment ◽  
Cns Lymphoma ◽  
High Dose ◽  
Consolidation Phase

The management of elderly patients suffering from primary central nervous system (CNS) lymphoma, who represent a rapidly growing population, is challenging. Despite the advances made in PCNSL treatment, the prognosis in older patients remains unsatisfactory. The high risk of systemic and CNS toxicity induced by a high-dose chemotherapy regimen and radiation therapy, respectively, limits the use of consolidation phase treatments in elderly patients and contributes to the poor outcome of these patients. Here, we review the current treatment strategies and ongoing trials proposed for elderly PCNSL patients.

scholarly journals Immunogenicity of high-dose influenza vaccination in patients with primary central nervous system malignancy

2018 ◽  
Vol 5 (3) ◽  
pp. 176-183
Author(s):  
Roy E Strowd ◽  
Gregory Russell ◽  
Fang-Chi Hsu ◽  
Annette F Carter ◽  
Michael Chan ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Influenza Vaccine ◽  
Elderly Patients ◽  
Influenza Vaccination ◽  
Standard Dose ◽  
High Grade Glioma ◽  
Cns Lymphoma ◽  
High Dose ◽  
Central Nervous System Malignancy

Abstract Background For cancer patients, rates of influenza-associated hospitalization and death are 4 times greater than that of the general population. Previously, we reported reduced immunogenicity to the standard-dose influenza vaccine in patients with central nervous system malignancy. In other poorly responding populations (eg, elderly patients), high-dose vaccination has improved efficacy and immunogenicity. Methods A prospective cohort study was designed to evaluate the immunogenicity of the Fluzone® high-dose influenza vaccine in brain tumor patients. Data on diagnosis, active oncologic treatment, and immunologic status (eg, CD4 count, CD8 count, CD4:CD8 ratio) were collected. All patients received the high-dose vaccine (180 µg). Hemagglutination inhibition titers were measured at baseline, day 28, and 3 months following vaccination to determine seroconversion (≥4-fold rise) and seroprotection (titer ≥1:40), which were compared to our prior results. Results Twenty-seven patients enrolled. Diagnoses included high-grade glioma (85%), CNS lymphoma (11%), and meningioma (4%). Treatment at enrollment included glucocorticoids (n = 8, 30%), radiation (n = 2, 7%), and chemotherapy (n = 9, 33%). Posttreatment lymphopenia (PTL, CD4 ≤ 200) was observed in 4 patients (15%). High-dose vaccination was well tolerated with no grade III-IV toxicity. Overall, seroconversion rates for the A/H1N1, A/H3N2, and B vaccine strains were significantly higher than in our prior study: 65% vs 37%, 69% vs 23%, and 50% vs 23%, respectively (all P < .04). Seroconversion was universally poor in patients with PTL. While seroprotection at 3 months declined in our prior study, no drop was observed following high-dose vaccination in this cohort. Conclusions The immunologic response to HD influenza vaccination was higher in this cohort than standard-dose influenza vaccination in our prior report. These findings mirror those in elderly patients where high-dose vaccination is the standard of care and raise the possibility of an immunosenescence phenotype.

scholarly journals Report of 5 Cases of Extramedullary Myeloma with Central Nervous System Involvement Treated with a Combination of Carfilzomib/Thalidomide/Dexamethasone As a First Line Treatment at a Single Institution in Mexico

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5704-5704 ◽  
Author(s):  
Ramiro Espinoza ◽  
Diana Berenice Nolasco ◽  
Sosa Alejandro ◽  
Zapata Nidia ◽  
Cervera Eduardo ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Multiple Myeloma ◽  
Nervous System ◽  
Treatment Guidelines ◽  
Conflicts Of Interest ◽  
Central Nervous System Involvement ◽  
Infectious Complications ◽  
High Dose ◽  
Single Institution ◽  
Number Of Patients

Abstract Extramedullary myeloma (EMM) is defined by the presence of plasma cells outside the bone marrow in a patient with multiple myeloma (MM) (Touzeau & Moreau, 2016). EMM is by itself a rare entity with cases involving central nervous system (CNS) being rarer, it has an estimated incidence of 1-1.8% of all MM cases (Majd et al, 2015). Its presentation in comparison to classical MM has an adverse prognosis including a shorter progression free survival (PFS) (Gozzetti et al, 2015) and overall survival (OS) with a mean life expectancy of 1.5-6 months (Majd et al, 2015). Currently there are not international treatment guidelines for this disease. The aim of this report is to illustrate our experience at a single institution in Mexico, presenting five cases of CNS-EMM treated with proteasome inhibitor (carfilzomib) in combination with thalidomide, dexamethasone plus radiotherapy. The patient's characteristics and the treatment regimen are shown in table 1 and 2. Within three months, following the criteria to the international multiple myeloma working group (IMMWG), all five patients accomplished a positive response (one partial response [PR] four very good partial responses [VGPR]), at sixth months two patients improved their response from previously PR to a VGPR and from VGPR to complete response (CR), one sustained its VGPR and after this period of time two patients had progressive disease (PD) and died due to infectious complications. After the tenth month a third patient also died of infectious complications. By the end of this report two patients still alive, one is being evaluated for autologous stem cell transplantation (ASCT) and the other one wasn't eligible according to European Group for Blood and Marrow Transplantation (EBMT) risk score and will continue treatment without ASCT. Previously reported cases in the literature with old chemotherapy regimens shown to have median survival of 1.5 months (Petersen et al 1999), nowadays the recommended therapy is based on triplet induction therapy followed by high-dose melphalan/ASCT, a triplet consolidation therapy and maintenance treatment with lenalidomide (Touzeau & Moreau, 2016); so far there is no evidence of proteasome inhibitors penetrating the blood brain barrier (Nooka et al, 2013) and this might be the reason why the literature strongly recommends the use of lenalidomide as this one does penetrate into the CSF after oral administration (Muscal et al, 2012), we did not use lenalidomide due to the high monetary cost of the treatment but instead we use thalidomide in combination with carfilzomib and dexamethasone with improved OS in three of our five patients (VGPR + CR). Despite the small number of patients presented in this report and the lack of cytogenetics or FISH information, we think this might be a good therapeutic approached in patients with CNS-EMM, especially in those scenarios with not accessible resources or absence of clinical trials. Further studies evaluating the addition of monoclonal antibodies (daratumumab, elotuzumab) need to be done in order to improve the OS and PFS in this group of patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals CENTRAL NERVOUS SYSTEM RELAPSE OF MULTIPLE MYELOMA

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Maria Qubtia ◽  
Muhammad Umer Nasir ◽  
Memoona Mian ◽  
Abdul Hameed
Keyword(s):  
Central Nervous System ◽  
Multiple Myeloma ◽  
Nervous System ◽  
Initial Response ◽  
Complete Response ◽  
Neurological Status ◽  
Best Supportive Care ◽  
High Dose ◽  
Central Nervous System Relapse ◽  
Dismal Prognosis

Multiple myeloma (MM) is a plasma cell disorder primarily involving bone marrow. Extramedullary involvement is less common, with central nervous system (CNS) myelomatosis being a rare entity and such presentation carries extremely dismal prognosis. We present case of a 40 years old male with MM who was initially treated with 6 cycles of Cyclophosphamide, Thalidomide and Dexamethasone resulting in complete response. 2 years later he presented with CNS myelomatosis and scrotal involvement and was initially treated with Bortezomib and dexamethasone, cranial irradiation and intrathecal Methorexate, Cytarabine, Hydrocortisone (TRIO IT), along with radical orchiectomy and testicular radiation during the course of treatment. However, after initial response his disease showed clinical and radiological progression after 4 months of therapy. He was switched to high dose Methotrexate (HD-MTX) with TRIOITand later Lenalidamide and dexamethasone (Len/dex) was added to the above regimen. He continued to show good clinical response but his cytology remained persistently positive, therefore, HD-MTX was discontinued in the later course of treatment. Subsequently he was started on best supportive care only, when his neurological status deteriorated further. He survived almost 9 months after a diagnosis of CNS myelomatosis. Patients with multiple myeloma, presenting with neurological symptoms should always be investigated for the possibility of CNS MM. CNS relapse is a fatal disease with poor prognosis. Recommended treatment must include a systemic anti-MM regimen that crosses the BBB (ideally Immunomodulatory drugs (IMiDs) IMiDs-dexamethasone based therapy), CNS irradiation and intrathecal chemotherapy.Key words: Multiple myeloma, central nervous system myelomatosis, therapy

scholarly journals Consolidation Treatment for Primary Central Nervous System Lymphoma: Which Modality for Whom?

2020 ◽  
pp. 1-14
Author(s):  
Osnat Bairey ◽  
Liat Shargian-Alon ◽  
Tali Siegal
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Real Life ◽  
Central Nervous System Lymphoma ◽  
Whole Brain Radiotherapy ◽  
Progression Free Survival ◽  
The Elderly ◽  
High Dose ◽  
Brain Radiotherapy ◽  
Randomized Studies

Primary central nervous system lymphoma is a rare aggressive disease that largely affects elderly patients and is associated with poor prognosis. The optimal treatment approach is not yet defined and it consists of induction and consolidation phases. The combination of high-dose (HD) methotrexate-based chemotherapy followed by whole-brain radiotherapy (WBRT) prolongs the median progression-free survival (PFS) and overall survival 2- to 3-fold as compared to WBRT alone but is associated with significant delayed neurotoxicity. Alternative strategies are being investigated in order to improve disease outcomes and spare patients the neurocognitive side effects. These include reduced-dose WBRT, non-myeloablative HD chemotherapy, or HD chemotherapy with autologous stem cell transplantation (HDC/ASCT). There are no randomized studies that compare all these consolidation regimens head to head but recently HDC/ASCT has been evaluated versus WBRT in prospective randomized studies. These studies proved that WBRT and HDC/ASCT yield similar 2-year PFS with preserved or improved cognitive function after HDC/ASCT. Yet, the proportion of patients treated with such intensive consolidation is low, both in real life and in specialized centers, leaving many unsettled issues. This review is appraising current dilemmas related to the choice of consolidating therapeutic modalities, their associated acute and delayed toxicity, and future prospects for alternative approaches in the elderly.

scholarly journals Efficacy and Safety of Dose Attenuated CHOP Chemotherapy for Peripheral T-Cell Lymphoma in Elderly Patients

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3953-3953 ◽  
Author(s):  
Eun-Ji Choi ◽  
Dok Hyun Yoon ◽  
Chan-Sik Park ◽  
Jooryung Huh ◽  
Sang-wook Lee ◽  
...  
Keyword(s):  
T Cell ◽  
Elderly Patients ◽  
Dose Reduction ◽  
Cell Lymphoma ◽  
Performance Status ◽  
The Elderly ◽  
T Cell Lymphoma ◽  
Free Survival ◽  
Full Dose ◽  
Grade 3

Abstract Background Peripheral T-cell lymphoma (PTCL) is an uncommon disease entity that accounts for 10-15% of all non-Hodgkin lymphomas (NHL). Except for anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL), the median age of patients ranges between 5th to 6th decades of life. Unfortunately, substantial numbers of the elderly patients are unable to tolerate full dose chemotherapy due to comorbidities or poor functional status. In this respect, we aimed to evaluate the efficacy and safety of the dose attenuated CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) chemotherapy in the elderly PTCL patients. Methods We analyzed data from patients with newly diagnosed PTCL aged over 65 years who presented to our institute between April 2001 and December 2014. NK/T cell lymphoma and mycosis fungoides were excluded from the study. Forty three patients were treated with the dose attenuated CHOP, which is a combination of cyclophosphamide (562.5 mg/m2 for 1 day, 25% dose reduction from full dose), doxorubicin (37.5 mg/m2 for 1 day, 25% dose reduction from full dose), vincristine (1.4 mg/m2 for 1 day) and prednisolone (50 mg bid for 5 days). Results The median age was 72 years (range 65-86). Among the forty three patients, PTCL-not otherwise specified (NOS) accounted for 62.8% (n=27), AITL for 16.3% (n=7), ALK-negative ALCL for 11.6% (n=5), and enteropathy-associated T cell lymphoma (EATL) for 9.3% (n=4), respectively. Although 79.1% (n=34) of patients had good performance status (Eastern Cooperative Oncology Group (ECOG) performance status <2), 93.0% (n=40) were in advanced stage (> Ann Arbor stage II). The overall response rate (ORR) and complete response (CR) rate was 77.8% and 52.8%, respectively. With a median follow-up period of 50.1 months (range 16.4-83.8), the 5-year event-free survival (EFS) and overall survival (OS) was 31.1% and 45.1%. The 5-year relapse-free survival (RFS) in those who achieved CR was 57.4%. Involvement of extranodal sites (≥2) (P=0.007 and hazard ratio [HR] 1.76 for OS, P=0.026 and HR 2.09 for EFS) was an independent prognostic factor for both EFS and OS. The grade 3 and 4 adverse events were consistent with the expected toxic effects of CHOP chemotherapy. Grade 3 or 4 neutropenia and thrombocytopenia was observed in 71.4% and 19.0%, respectively. However, 45.2% experienced febrile neutropenia. In addition, twelve patients died from treatment-related toxicities. Another 10 died from progression of disease, and the other two from unknown causes. Conclusion Dose attenuated CHOP with 25% dose reduction of cyclophosphamide and doxorubicin for elderly PTCL doesn't seem to diminish response or survival rates, which resulted in at least comparable efficacy outcomes to the prior reports (J Clin Oncol 2008;26:4124-4130). However, it is still associated with significant toxicities with high treatment-related mortalities. Novel treatment strategies for these vulnerable elderly patients are urgently needed. Disclosures No relevant conflicts of interest to declare.

Efficacy and Safety of Thalidomide in Patients with Complicated Central Nervous System Tuberculosis: A Systematic Review and Meta-Analysis

2021 ◽  
Author(s):  
Prateek Kumar Panda ◽  
Pragnya Panda ◽  
Lesa Dawman ◽  
Rakesh Kumar Sihag ◽  
Indar Kumar Sharawat
Keyword(s):  
Systematic Review ◽  
Central Nervous System ◽  
Nervous System ◽  
Adverse Effects ◽  
Single Case ◽  
Case Reports ◽  
Controlled Trial ◽  
Random Effect ◽  
High Dose ◽  
Qualitative Synthesis

Thalidomide, an anti-inflammatory and immunomodulatory agent, has a potential role in cases with central nervous system tuberculosis (CNS-TB) with paradoxical reactions. Although several articles have described the use of thalidomide in CNS-TB, no systematic review has been performed in this regard. Different electronic databases were searched for articles describing the use of thalidomide in patients with CNS-TB. For determining pooled estimates in the quantitative review, studies with a minimum sample size of 5 were only considered, whereas for qualitative synthesis even single case reports were included. Fixed or random effect models were used suitably depending on the degree of heterogeneity. Fourteen articles describing a total of 107 patients (98 children and 9 adults) were selected from 156 records. A favorable clinical response was observed in 89% of patients with CNS-TB who had paradoxical reactions refractory to corticosteroids. Majority of the studies used a dose of 2–6 mg/kg/day and around 24% suffered from at least one adverse effect, with a mortality of 5%. Predominant adverse effects were rash (9.5%), neuropathy (6%), and elevated liver transaminases (9.5%). Only one placebo-controlled trial has been performed till now, which showed that high-dose thalidomide has numerous adverse effects, without any clinically significant improvement as compared with placebo. While in HIV-positive patients with TB-immune reconstitution inflammatory syndrome thalidomide was helpful in around 82% of cases. Low-dose thalidomide is helpful in patients with CNS-TB who had a paradoxical reaction and unresponsive to corticosteroids. Large, randomized trials are needed to provide more concrete information regarding the safety and efficacy of thalidomide.

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