scholarly journals Analysis of Falls in Older Adults with Multiple Myeloma Undergoing First-Line Therapy

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5886-5886
Author(s):  
Kelly L. Schoenbeck ◽  
Tanya M. Wildes ◽  
Mark A. Fiala
Keyword(s):  
Older Adults ◽  
Multiple Myeloma ◽  
Peripheral Neuropathy ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Increased Risk ◽  
Risk Of Falls ◽  
Falls In Older Adults ◽  
First Line Treatment

Background: Patients with multiple myeloma are frequently treated with bortezomib, a proteasome inhibitor, which is associated with treatment-related peripheral neuropathy. Older adults are at increased risk of falls compared to the general population, often leading to associated morbidity and mortality. While an association between peripheral neuropathy and falls in older adults is well-established, the relationship between bortezomib and falls in older multiple myeloma patients is unknown. Our primary aim was to determine if older patients with multiple myeloma treated with bortezomib as first-line therapy had an increased incidence of falls within the first 12 months after starting treatment. Our secondary aim was to assess the overall survival of patients who fell compared to those who did not among patients who lived more than 12 months after initiating treatment. Methods: We analyzed the SEER-Medicare database for all patients 65 years old or older diagnosed with multiple myeloma between 2007 and 2013 and were enrolled in fee-for-service Medicare part A, B and D plans. The patients' corresponding Medicare claims data were analyzed through 2014 for myeloma treatments, fall claims, and covariates of interest. The primary outcome was accidental falls (E880-E888) occurring between 14 days to 12 months after starting multiple myeloma treatment. First-line therapy was defined as any anti-myeloma treatment administered within 14 days of starting multiple myeloma treatment, with bortezomib treatment being the focal independent variable. Cox regression was performed to determine the relative risk of having a fall after controlling for other covariates. Patients who started bortezomib after first-line therapy were censored at time of bortezomib commencement. The survival analysis included only patients who survived more than 12 months of starting treatment to allow landmark analysis of falls in the first year. Results: Of 4,084 older adults with new multiple myeloma diagnoses undergoing first-line therapy, the median age was 75 (range 65-97) with 51% males. Bortezomib was used in first-line therapy for 2,052 (50%) patients, of which 157 (8%) patients experienced a fall within 12 months after starting treatment compared to 102 (5%) of patients not receiving bortezomib (p < 0.001). Bortezomib was associated with a 28% increase risk of falls (HR 1.29; 95% CI 1.00-1.65; p = 0.047). In multivariate analysis, bortezomib was not associated with an increased incidence of falls after controlling for age, gender, race, proxies for Charlson Comorbidity Index (CCI) and poor performance status, pre-existing peripheral neuropathy, falls within the 12 months prior to starting first-line myeloma treatment, depression, polypharmacy, and first-line treatment with lenalidomide (Table 1). Advancing age, history of fall(s), depression, and polypharmacy (defined as more than 10 unique prescription medications at initiation of first-line treatment), were all associated with an increased risk of falls, consistent with prior literature. In a landmark analysis of those who survived 12 months following the start of treatment, a fall was associated with a 26% increased risk of hazard for death (aHR 1.26; 95% CI 1.02-1.56; p = 0.033) after controlling for other covariates. The median OS of those with a fall was 35.7 months (95% CI 29.1-48.4) compared to 49.1 months (95% CI 47.1-52.8) for those without (p < 0.0001). Conclusion: In older adults with multiple myeloma, treatment with bortezomib was not associated with increased risk of a patient having a diagnostic code for falls. However, experiencing a fall within the year after starting treatment was associated with decreased overall survival. Limitations of the study include that the incidence of falls is likely underestimated in billing data, given prior data from our group showing a rate of self-reported falls of 26% in the year after diagnosis. Additional research, including prospective trials involving fall assessments, should be considered in older patients with multiple myeloma. Disclosures Wildes: Janssen: Research Funding; Carevive: Consultancy. Fiala:Incyte: Research Funding.

Bortezomib with HIG-Dose Dexamethasone as First Line Therapy in Patients with Multiple Myeloma Candidates to High-Dose Therapy.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3595-3595 ◽  
Author(s):  
Alessandro Corso ◽  
Luciana Barbarano ◽  
Silvia Mangiacavalli ◽  
Luigi Montalbetti ◽  
Paola Brasca ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Peripheral Neuropathy ◽  
Light Chain ◽  
High Dose ◽  
First Line ◽  
High Dose Therapy ◽  
First Line Therapy ◽  
Line Therapy

Abstract Introduction: A phase II multi-center study was performed to investigate the efficacy of Bortezomib with high-dose dexamethasone (Vel-Dex) as induction therapy in multiple myeloma (MM) patients (pts) candidates to high-dose therapy. Methods: Patients were planned to receive 4 courses of Vel-Dex (Bortezomib 1.3 mg/m2 i.v. on days 1, 4, 8, 11; oral Dexamethasone 40 mg on days 1–4 and 8–11 every 3 weeks), followed by 2 courses of DCEP 4 weeks apart with stem cell collection, and a single autologous transplant with melphalan 200 mg/m2. Patients were untreated, aged ≤65 years, with Durie-Salmon stage III, II, or I in progression. Criteria of response were: CR: negative serum/urine immunofixation with &lt;5% bone marrow plasmacytosis (BMPC); nCR: positive serum/urine immunofixation with &lt;5% BMPC; VGPR/PR: reduction of at least 90%/50% of serum/urine monoclonal component (MC), and of BMPC. Adverse events (AE) were graded by the NCI-CTC version 3.0. Mann-Whitney U test was used to correlate response and main prognostic parameters. Results: From March 2006 to June 2007, 52 out of the 54 planned pts entered the protocol. Patient characteristics at enrolment were: male/female 33/19; median age 57 years (37–65); IgG/IgA/light-chain 33/9/10 pts; stage III/II/I in progression 44/5/3 pts; ISS I/II/III 21/14/17 pts; cytogenetic analysis showed del 13 in 54%, t (4;14) in 15%. Thirty-nine of 52 enrolled pts are evaluable for efficacy and toxicity after 4 Vel-Dex courses. Six pts were withdrawn (3 for progression, 2 for toxicity, 1 patient withdrew informed consent). Overall response rate (ORR) was 85%, with 67% major responses (CR 33%, nCR 26%, VGPR 8%), PR 18%, stable disease 7%, progression 8%. No statistically significant correlation was found between response and either age, stage, ISS, or unfavorable cytogenetics. Friedman ANOVA (p=0.00001) and Wilcoxon Matched Pairs (p&lt;.05) tests showed a statistically significant progressive decrease of serum MC after each Vel-Dex cycle. Urine MC and serum free light chain ratio showed a strikingly rapid reduction after the first course with no further statistically significant decrease during the following courses. Regarding toxicity, NCI grade 1 or 2 AE were: infection (19), constipation (16), peripheral neuropathy (13), diarrhea (9), gastritis (6), nausea (5). NCI grade 3 AE were: infection (9) with 5 varicella-zoster, peripheral neuropathy (4), cardiac arrhythmia (2). A single grade 4 AE (fatal sepsis) occurred. At the time of this analysis, 25 pts completed the stem cell mobilization phase. All pts collected adequate number of stem cells (median CD34+ cells 6.2x106/kg, range 3.5–18.0x106/kg, median number of collection procedures 1). Discussion: This study shows that Vel-Dex as first line therapy produces high response rates in MM pts (ORR 85%, major response 67%). Toxicity was generally predictable and manageable. Stem cells were successful harvested in all patients. Vel-Dex appears an effective and safe pre-transplant treatment for younger MM patients.

scholarly journals Efficiency of lenalidomide, bortezomib and prednisone (RVP) in patients with newly diagnosed multiple myeloma

2019 ◽  
Vol 14 (1) ◽  
pp. 14-19 ◽  
Author(s):  
K. A. Belousov ◽  
T. A. Mitina ◽  
Yu. Yu. Chuksina ◽  
A. K. Golenkov ◽  
E. V. Kataeva ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Objective Response ◽  
Hematological Toxicity ◽  
Efficacy And Safety ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

Objective: to study the efficacy and safety of the antitumor RVP program (lenalidomide, bortezomib, prednisone) as a first-line therapy in patients with multiple myeloma (MM). Materials and methods. A prospective study involved 39 patients with MM (15 women, 24 men), median age 61 years (30–76 years). All patients had Durie–Salmon stage III disease. According to the paraprotein isotype variant, 19 patients (48.7 %) had Gk myeloma, 8 (20.5 %) had Gλ, 4 (10.2 %) – Ak, 1 – Aλ, 1 – Dk, 1 – paraproteinemia Bens-Jones k and 1 – Bens-Jones λ, 2 – Dλ, and 2 patients – nonsecreting MM. The average level of plasma cells in the bone marrow was 31.7 % (0.8–80.0 %). In 14 (35.8 %) patients there were plasmacytomas of various localization (spine, cranial bones, clavicle, pleura). Nine (23.0 %) patients had renal failure, requiring the start of renal replacement therapy. The average Karnovsky index in the study group was 50 %. All patients received RVP therapy (lenalidomide 25 mg in 1–14 days, bortezomib 1.3 mg subcutaneously in 1, 4, 8, 11 days, prednisolone 60 mg/m2; the interval between courses was 42 days) as the first line therapy. Evaluation of therapy efficacy, characterized by overall survival, objective response rates (the number of complete, very good partial and partial remissions) was performed after 6 treatment courses. Results. The median follow-up was 15 months; the median of overall survival was not achieved. Objective antitumor response achieved in 29 (74.3 %) patients, including complete remissions in 3 (7.6 %), very good partial remissions – in 7 (17.9 %), partial remissions – in 19 (48.7 %) patients. In 2 out of 9 patients who received renal replacement therapy, independence from dialysis therapy was achieved. Cases of III–IV stage hematological and non-hematological toxicity in the study were not noted. Conclusion. The antitumor RVP program showed high efficacy and safety as a first-line therapy in a non-selective group of patients, including those with a complicated MM course.

The combination of thalidomide and intermediate-dose dexamethasone is an effective but toxic treatment for patients with primary amyloidosis (AL)

Blood ◽  
2005 ◽  
Vol 105 (7) ◽  
pp. 2949-2951 ◽  
Author(s):  
Giovanni Palladini ◽  
Vittorio Perfetti ◽  
Stefano Perlini ◽  
Laura Obici ◽  
Francesca Lavatelli ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cells ◽  
Primary Amyloidosis ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Symptomatic Bradycardia ◽  
Intermediate Dose

AbstractBased on the efficacy of thalidomide in multiple myeloma and on its synergy with dexamethasone on myeloma plasma cells, we evaluated the combination of thalidomide (100 mg/d, with 100-mg increments every 2 weeks, up to 400 mg) and dexamethasone (20 mg on days 1-4) every 21 days in 31 patients with primary amyloidosis (AL) whose disease was refractory to or had relapsed after first-line therapy. Eleven (35%) patients tolerated the 400 mg/d thalidomide dose. Overall, 15 (48%) patients achieved hematologic response, with 6 (19%) complete remissions and 8 (26%) organ responses. Median time to response was 3.6 months (range, 2.5-8.0 months). Treatment-related toxicity was frequent (65%), and symptomatic bradycardia was a common (26%) adverse reaction. The combination of thalidomide and dexamethasone is rapidly effective and may represent a valuable second-line treatment for AL.

Outcomes with different administration schedules of VRD as first-line therapy in multiple myeloma: a retrospective analysis

2019 ◽  
Vol 19 (10) ◽  
pp. e203
Author(s):  
Joselle Cook ◽  
Surbhi Sidana ◽  
Wilson Gonsalves ◽  
Morie A. Gertz ◽  
Francis Buadi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Retrospective Analysis ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Administration Schedules

Longitudinal Evaluation of Minimal Residual Disease in Patients with Multiple Myeloma who Achieve Complete Response After First Line Therapy

2019 ◽  
Vol 19 (10) ◽  
pp. e185-e186
Author(s):  
Ioannis V. Kostopoulos ◽  
Efstathios Kastritis ◽  
Aristea-Maria Papanota ◽  
Paraskevi Micheli ◽  
Panagiotis Malandrakis ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Complete Response ◽  
First Line ◽  
Longitudinal Evaluation ◽  
First Line Therapy ◽  
Line Therapy ◽  
Minimal Residual

scholarly journals Quinagolide – a valuable treatment option for hyperprolactinaemia

2006 ◽  
Vol 154 (2) ◽  
pp. 187-195 ◽  
Author(s):  
Anne Barlier ◽  
Philippe Jaquet
Keyword(s):  
Dopamine Agonists ◽  
Pharmacological Intervention ◽  
Plasma Prolactin ◽  
Dosing Regimen ◽  
First Line ◽  
First Line Therapy ◽  
Gonadal Dysfunction ◽  
Line Therapy ◽  
Increased Risk ◽  
History Of Use

Hyperprolactinaemia is characterised by gonadal dysfunction, including infertility and reduced libido and, if left untreated, is associated with an increased risk of long-term complications, such as osteoporosis. The first-line therapy for patients with hyperprolactinaemia is pharmacological intervention with a dopamine agonist. Currently, there are three dopamine agonists available for hyperprolactinaemia therapy: bromocriptine, quinagolide and cabergoline. Bromocriptine has a long history of use; however, a range of 5–18% of patients are reported to show bromocriptine resistance, with only partial lowering of plasma prolactin levels and an absence of tumour shrinkage. The newer dopamine agonists, quinagolide and cabergoline, offer improved efficacy over bromocriptine, with a lower incidence of adverse events. Quinagolide and cabergoline have also demonstrated efficacy in many patients intolerant or resistant to bromocriptine. Thus, the selection of dopamine agonists available provides more than one option for pharmacological intervention of hyperprolactinaemia. This review discusses the clinical use of quinagolide in comparison to other dopamine agonists for hyperprolactinaemia therapy. Quinagolide may improve patient compliance to treatment owing to its reduced side effect profile, simple and rapid titration over just 7 days, once-daily dosing regimen and easy to use starter pack (available in some countries). Quinagolide offers an additional benefit for patients wishing to become pregnant, as it can be used until the point of confirmation of pregnancy. Therefore, as a well tolerated and effective therapy, with a simple dosing regimen, quinagolide should be considered as a first-line therapy in the treatment of hyperprolactinaemia.

Thalidomide Plus Dexamethasone for Untreated Newly Diagnosed Multiple Myeloma Patients and Deep Vein Thrombosis.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5093-5093 ◽  
Author(s):  
Victor H. Jiménez ◽  
Virginia J. Domínguez ◽  
Eduardo E. Reynoso
Keyword(s):  
Multiple Myeloma ◽  
Deep Vein Thrombosis ◽  
Oral Dose ◽  
Newly Diagnosed ◽  
First Line ◽  
Factor V Leiden Mutation ◽  
Vein Thrombosis ◽  
First Line Therapy ◽  
Line Therapy ◽  
Deep Vein

Abstract Background The combination of thalidomide/dexamethasone (TD) induces remission in approximately 70% of previously untreated patients with low or intermediate tumor mass. TD appeared superior to previous programs because of the high response rate and reasonable survival and its low frequency of serious complications. The aim of our study was to assess the efficacy of thalidomide plus dexamethasone as first line therapy and the incidence of deep vein thrombosis. Material and methods Patients with newly diagnosed and symptomatic MM (untreated patients) were evaluated. We enrolled all patients who fulfilled entire criteria for multiple myeloma between January 1998 and December 2005. Patients were divided into 2 groups: thalidomide plus dexamethasone (TD) and VAD group. The present study is a prospective, descriptive, longitudinal and observational one. Thalidomide was prescribed in an oral dose of 100 mg qhs and increased by 50 mg every 7 days to a maximum dose of 300 mg, depending on side effects. Dexamethasone was given in an oral dose of 20 mg/m2 each morning after breakfast on days 1–4, 9–12 and 17–20, followed by 10 days without therapy prior to the next cycle. Treatment with the combination was continued for at least 6 months or until the earliest occurance of maximum plateau of myeloma protein reduction, autologous transplant-supported intensification or other treatments. VAD was given as an Out-patient regimen including: vincristine (0.4mg/day, continuous IV), doxorubicin (9mg/m2/day, continuous IV) and dexamethasone (40 mg/day PO) with a median of 6 courses. Citrate plasma was used to investigate coagulation and anticoagulation parameters. Results Sixty newly diagnosed multiple myeloma patients were included in the study, 35 (58%) male and 25 (42%) female, aged 45–85 (mean 63). Underlying diagnosis was IgG MM in 44 (73.3%), IgA in 12 (20%) and light chain disease in 4 (6.7%). Clinical characteristics were similar for both groups. According to Durie Salmon criteria patients were grouped into: IA (n6, 10%), IB (n3, 5%), IIA (n12, 20%), IIB (n6, 10%), IIIA (n19, 31.6%) and IIIB (n14, 23.4%). The frequency of response (CR, NCR/VGPR and PR) in the group of thalidomide and dexamethasone was 73% being higher than VAD (53%)p0.005. CR was observed in 5 patients treated with thalidomide/dexamethasone (16%). Thrombosis complications DVT was observed in 7 patients. DVT occurred in 4 patients treated with TD and 3 with VAD. From the last 40 patients, 5 presented APC-R and 3 of them developed DVT. A significant shorter time to DVT was observed in patients exposed to VAD chemotherapy (first 2 cycles p 0.007). Patients developing APC-R were tested for Factor V Leiden mutation resulting negative. After patients developed any response criteria were retested for acquired activated protein C resistance, all of them went back to normal. Finally we conclude TD is an effective, less toxic therapy in comparison with VAD as first line therapy and in order to reduce incidence of DVT effective prophylactic anticoagulation should be implemented in all controlled trials, at least during the first few cycles of treatment.

A Pilot Study of Lenalidomide and Dexamethasone as First Line Therapy in Patients with Primary Plasma Cell Leukemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4951-4951
Author(s):  
Pellegrino Musto ◽  
Maria Teresa Petrucci ◽  
Fortunato Morabito ◽  
Francesco Nobile ◽  
Fiorella D'Auria ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Early Response ◽  
Plasma Cell Leukemia ◽  
Cell Leukemia ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Primary Plasma Cell Leukemia

Abstract Abstract 4951 Background Primary Plasma Cell Leukemia (PPCL) is an aggressive, rare variant of multiple myeloma, with clinical, molecular and phenotypic peculiarities, which accounts approximately for 2% to 4% of all myeloma diagnoses. The prognosis of PPCL patients is usually poor, with less than half of patients responding to conventional chemotherapy and a median survival of 7 months. Even by using autologous or allogeneic transplant procedures, survival generally does not exceed three years. Bortezomib has recently provided some promising results in this setting, but, given all the above, new treatments for PPCL are greatly awaited. Lenalidomide is a new immunomodulating agent with great efficacy in multiple myeloma, especially when associated with dexamethasone or other drugs. There are, indeed, some sporadic case reports of PPCL patients treated with lenalidomide as salvage therapy, but no data are currently available on the use of this drug as first line therapy in this disease. Patients and Methods On March, 2009, we started an open label, prospective, multicenter, exploratory, single arm, two-stage study aiming to evaluate safety and antitumor activity of the lenalidomide/low dose dexamethasone combination (Rd), as first line therapy in patients with PPCL. The primary endpoint was early response rate according to International Uniform Criteria. The secondary endpoints were TTP, PFS, OS, percentage of eligible PPCL patients able to collect peripheral blood stem cells and to undergo autologous or allogeneic stem cells transplantation after Rd, serious and severe adverse event rate. According to this study protocol, all eligible, newly diagnosed adult patients with PPCL receive Lenalidomide at a dose of 25 mg daily for 21 days every 28 days. Oral dexamethasone is administered at a dose of 40 mg daily on days 1, 8, 15, and 22 for each 28-day cycle. After 4 cycles, patients who achieve at least PR and not eligible for autologous or allogeneic stem cell transplantation, continue with Rd until clinically appropriate (disease progression, unacceptable toxicity, patient's decision to leave the protocol). In these patients, a maintenance dose of lenalidomide alone equal to 10 mg/die days 1-21 every month is considered after at least 8 full dose Rd cycles. Patients responding after 4 Rd cycles and eligible for transplant procedures, proceed according to single Centre transplant policy. Patients not responding after 4 cycles or progressing under Rd treatment are considered off-study. Appropriate contraception methods and anti-thrombotic prophylaxis are planned. Results Four enrolled patients (1 male, 3 female, mean age 65 years, range 58-69) are currently evaluable for early response. All had unfavourable cytogenetics, including del13, t(4;14), t (14;16), or a complex karyotype. Circulating plasma cells ranged from 4.4 to 9.2 ×10e9/l. One patient had at baseline a moderate degree of renal failure (serum creatinine levels 2 mg/dl). After at least 2 Rd cycles (range 2-4), two PR and two VGPR were achieved (overall response rate 100%), with disappearance or near complete reduction of circulating plasma cells in all cases. The most relevant toxicities were grade 3 neutropenia and pneumonia, occurring in one patient and resolved by appropriate lenalidomide dose reduction, introduction of G-CSF and antibiotic therapy. One patient died in PR, due to causes unrelated to PPCL or treatment. As, according to the Simon, two-stage design adopted, more than two responses occurred within the first ten patients enrolled (stage 1), a total of 22 PPCL subjects will be accrued to complete the stage 2 of the trial. Conclusions These findings, though very preliminary, suggest that the combination of lenalidomide and dexamethasone may be a safe and promising initial therapy for PPCL patients, which can rapidly control the disease and could permit to perform following single patient-adapted therapeutic strategies. An update of this study, including molecular data, a larger number of patients and a longer follow-up, will be presented at the Meeting. Disclosures Musto: Janssen-Cilag: Honoraria; Celgene: Honoraria, Research Funding. Off Label Use: Lenalidomide is approved in Italy for advanced multiple myeloma, not for plasma cell leukemia. This is a clinical trial registered at AIFA (Italian regulatory Agency for Drugs), EudraCT No. 2008-003246 28. Petrucci:Janssen-Cilag: Honoraria; Celgene: Honoraria. Morabito:Celgene: Honoraria; Janssen-Cilag: Honoraria. Cavo:Celgene: Honoraria; Janssen-Cilag: Honoraria. Boccadoro:Celgene: Honoraria; Janssen-Cilag: Honoraria. Palumbo:Celgene: Honoraria; Janssen-Cilag: Honoraria.

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