Clinical Efficacy of a Bortezomib, Cyclophosphamide and Dexamethasone Compared with Bortezomib, Cyclophosphamide, Thalidomide and Dexamethasone in Patients with Relapsed or Refractory Multiple Myeloma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1868-1868
Author(s):  
Jae-Sook Ahn ◽  
Deok-Hwan Yang ◽  
Joon Ho Moon ◽  
Sang Kyun Sohn ◽  
Sung-Hoon Jung ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Herpes Zoster ◽  
Partial Response ◽  
Adverse Events ◽  
Conflicts Of Interest ◽  
Sensory Neuropathy ◽  
Salvage Regimen ◽  
Refractory Multiple Myeloma ◽  
Grade 3 ◽  
Acyclovir Prophylaxis

Abstract Abstract 1868 Backgrounds & Aims: Salvage therapy such as bortezomib, cyclophosphamide, thalidomide and dexamethasone (Vel-CTD) showed an effective regimen in patients with relapsed or refractory multiple myeloma (MM). However, toxicities of this regimen due to combination bortezomib and thalidomide interrupt the consecutive treatments in a few patients. Therefore, we compared the clinical responses and toxicities between bortezomib, cyclophosphamide and dexamethasone (Vel-CD) and Vel-CTD in patients with relapsed or refractory MM patients, retrospectively. Methods: Eighty-six patients received at least 2 cycles of treatment with Vel-CTD (bortezomib 1.3 mg/m2 i.v. on D1, 4, 8 and 11; cyclophosphamide 150 mg/m2 orally on D1-4; thalidomide 50 mg/day orally every day; and dexamethasone 20 mg/m2 i.v. on D1, 4, 8 and 11 for every 3 weeks) and 67 patients with Vel-CD, which is the same regimen except thalidomide. Vel-CD group was only received low-dose acyclovir for prevention of herpes zoster. Results: 17/67 (25%) and 10/86 (12%) of light chain disease was enrolled in Vel-CD and Vel-CTD group respectively (p=0.027) and there was no statistical difference at baseline demographic and disease characteristics between two groups in the others. The median time from diagnosis to treatment in Vel-CD and Vel-CTD was 15.6 months (range, 2–250 months) and 15.7 months (range, 1–230 months), respectively (p=0.54). The median number of treatment cycles was 6 cycles (range, 2–18) in Vel-CD and 8 cycles (range, 2–24) in Vel CTD group, and the number of cycles delivered was 430 and 678, respectively. The overall response rates (≥PR) of Vel-CD and Vel-CTD group were 88% and 90% ( 49% and 48% of complete response, 9% and 14% of very good partial response, 30% and 28% of partial response), respectively (each, p>0.05). There was no difference in progression free survival (p=0.69) and overall survival (p=0.49). Grade 3 or more hematologic adverse events occurred in the same proportion of patients in the both group. In non hematologic toxicities profiles, Vel-CTD group (14%) showed the higher proportion of grade 3 or more sensory neuropathy compared with Vel-CD group (3%) (p=0.02). Dose adjustment of bortezomib in Vel-CD and Vel-CTD were 40% (27/67) and 41%(35/86), respectively (p=0.96). Two patients (3%) in Vel-CD group received acyclovir prophylaxis developed herpes zoster compared with 17 patients (20%) in Vel-CTD group they were not received acyclovir prophylaxis (p=0.002). Three patients showed thrombotic events (2: pulmonary thromboembolism, 1: acute myocardial infarction) in only Vel-CTD group despite aspirin prophylaxis (p=0.16). Conclusion: Vel-CD combination therapy in patients with relapsed or refractory MM is an effective and more tolerable salvage regimen compared with Vel-CTD in the aspect of comparable response rate, less non-hematologic toxicities especially thalidomide associated adverse events. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Clinical Outcome of Bortezomib Retreatment in Patients with Relapsed or Refractory Multiple Myeloma

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Jae-Sook Ahn ◽  
Sung-Hoon Jung ◽  
Seung-Shin Lee ◽  
Seo-Yeon Ahn ◽  
Deok-Hwan Yang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Sensory Neuropathy ◽  
Progression Free Survival ◽  
Complete Response ◽  
Free Survival ◽  
Refractory Multiple Myeloma ◽  
Grade 3 ◽  
Peripheral Sensory ◽  
Good Partial Response

This retrospective study investigated the clinical efficacy and safety of bortezomib retreatment in patients with relapsed or refractory multiple myeloma (MM). A total of 30 patients who relapsed or progressed after≥6 months since the last dose of their previous bortezomib therapy were included in this study. During the median 6 cycles (range: 2–12) of bortezomib retreatment, 10 (33.3%), 2 (6.7%), and 6 (20.0%) patients achieved complete response, very good partial response, and partial response, respectively. Grade 3 or 4 neutropenia (47.0%), thrombocytopenia (43.0%), anemia (10.0%), and peripheral sensory neuropathy (3.0%) were observed. The median time to progression, progression-free survival, and overall survival were 5.8 months (95% CI: 2.6–9.0), 5.5 months (95% CI: 4.2–6.8), and 13.4 months (95% CI: 6.1–20.7), respectively. Patients who received bortezomib retreatment≥12 months from initial last therapy had a 1-year OS rate of 65.8% (95% CI: 43.5–88.1) while patients receiving retreatment after 6–12 months interval had a 1-year OS rate of 41.7% (95% CI: 13.9–69.5) (P=0.038). In conclusion, this study demonstrates that retreatment with bortezomib is an effective strategy for patients with MM who relapsed at a long interval after initial bortezomib therapy.

A Prospective Randomized Phase I/II Study of Lenalidomide, Melphalan, Prednisone and Thalidomide (RMPT) for Relapsed/Refractory Multiple Myeloma Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2864-2864 ◽  
Author(s):  
Federica Cavallo ◽  
Alessandra Larocca ◽  
Maria Teresa Petrucci ◽  
Vincenzo Federico ◽  
Antonietta Pia Falcone ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Adverse Events ◽  
Phase I ◽  
Response Rate ◽  
Oral Prednisone ◽  
Hematologic Toxicity ◽  
Free Survival ◽  
Refractory Multiple Myeloma ◽  
Grade 3

Abstract Abstract 2864 Poster Board II-840 Background. New drug associations may improve patients outcome in relapsed/refractory multiple myeloma (MM). In newly diagnosed MM patients the addition of lenalidomide or thalidomide or bortezomib, to the standard oral melphalan and prednisone combination significantly increased response rate and event-free survival, showing synergistic effects. Aims. This is a multicenter, randomized, open label phase I/II trial designed to evaluate the safety/efficacy profile of the salvage treatment, Lenalidomide, Melphalan, Prednisone and Thalidomide (RMPT) in patients with relapsed/refractory myeloma. Methods. Oral lenalidomide was administered at 10 mg/day on days 1-21, in combination with oral melphalan at 0.18 mg/kg on days 1–4 and oral prednisone at 2 mg/kg on days 1–4. Thalidomide was administered at 50 mg/day (Arm A) or 100 mg/day (Arm B) on days 1-28. Each course was repeated every 28 days for a total of 6 courses. Maintenance therapy included Lenalidomide alone at 10 mg/day on days 1-21. Aspirin 100 mg/day was given as a prophylaxis for thrombosis. Results. Forthy-four patients with relapsed/refractory MM were enrolled in the study between May 2007 and March 2008, including 22 patients in arm A and 22 patients in arm B. After a median of 5 cycles 75% of patients achieved at least a partial response (PR), including 20% very good partial response (VGPR) and 14% near or complete response (nCR or CR). Among patients who received thalidomide 100 mg, the PR rate was 82% (including 23% VGPR and 23% CR/nCR). Higher response rate was observed among patients who received RMPT in first relapse. The 1-year-progression-free survival was 51,5% and the 1-year survival from study entry was 72%. Hematologic toxicity was the most frequent adverse event. Grade 3-4 hematologic adverse events included: neutropenia (68%), thrombocytopenia (36%) and anemia (32%). Grade 3-4 non hematologic adverse events included: infections (22,7%), neurological toxicity (4,5%) and fatigue (6,8%). No grade 3-4 thromboembolic events were reported. Conclusion. This is the first trial exploring the association of two immunomodulatory drugs, Thalidomide and Lenalidomide. RMPT is an active regimen in patients with relapsed/refractory MM. Toxicities were manageable and the incidence of neutrotoxcities was low. Updated results will be presented at the time of the meeting. Disclosures: Cavallo: CELGENE: Honoraria. Petrucci:CELGENE: Honoraria. Canepa:CELGENE: Honoraria. Boccadoro:CELGENE: CONSULTANCY, ADVISORY COMMITTEES, Research Funding. Palumbo:CELGENE: Honoraria.

PP455 Cost-effectiveness Of Ixazomib-Based Regimen Compared With Bortezomib-Based Regimen In Chinese Patients With Relapsed/Refractory Multiple Myeloma: A Retrospective Study

2020 ◽  
Vol 36 (S1) ◽  
pp. 36-37
Author(s):  
Pei Wang ◽  
Jing Li ◽  
Yang Yang ◽  
Peng Liu
Keyword(s):  
Multiple Myeloma ◽  
Adverse Events ◽  
Staging System ◽  
Chinese Patients ◽  
Disease Stage ◽  
Control Group ◽  
Therapeutic Effects ◽  
Lower Grade ◽  
Refractory Multiple Myeloma ◽  
Grade 3

IntroductionThe treatment of relapsed/refractory multiple myeloma (RRMM), a common hematological malignancy, remains a great challenge in China, partially due to the limited accessibility to novel agents and inadequate public health insurance coverage. Ixazomib, a novel oral proteasome inhibitor (PI), was approved by the China Food and Drug Administration (CFDA) for RRMM in 2018. While bortezomib, a traditional PI, is the recommended agent in the clinical guideline for MM. Here, we compared their costs and effectiveness.MethodsRRMM patients who has received an ixazomib-based regimen (at least 2 cycles) were analyzed. Using a propensity score matching method, we generated a control group of RRMM patients who received the bortezomib-based regimen. The criteria included the number of treatment lines, age, and the revised international staging system stage (R-ISS) which representing the disease stage for myeloma, and paired at a ratio of 1:2 (allowing one control to match multiples). The difference in hospitalization stay, grade 3/4 adverse events rates, overall response rate (ORR), mortality during treatment, and treatment costs was then compared.ResultsNineteen patients received ixazomib and twenty-seven that received bortezomib were included. The ixazomib-group demonstrated a shorter hospital stay (9 days versus 27 days, p < 0.001), lower grade 3–4 adverse events rates (42.1% versus 55.6%, p < 0.001), higher ORR (63.2% versus 48.1%, p = 0.228), and lower mortality rate during treatment (0% versus 7.4%, p = 0.169) than that of bortezomib-group. The ixazomib group had lower total costs (127,620CNY versus 156,424CNY [18,033USD versus 22,103USD], p > 0.05), lower drug costs (98,376CNY versus 103,307CNY [13,901USD versus 14,598USD], p > 0.05), and the lower costs of supportive treatment (5,507CNY versus 14,701 CNY [778USD versus 2,077USD], p < 0.001). Only in terms of self-funded costs, the bortezomib-based regimen was significantly lower (37,127CNY versus 11,521CNY [5,246USD versus 1,628USD], p < 0.001).ConclusionsCompared with the bortezomib-based regimen, the ixazomib-based regimen has better therapeutic effects on MM patients while saving costs. Hence, it may be preferable for use in the treatment of RRMM in China.

The Efficacy and Safety of Immunomodulatory Drugs in Multiple Myeloma Maintenance Therapy: Results of a Meta-Analysis

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3477-3477
Author(s):  
Yucai Wang ◽  
Fang Yang ◽  
Wenwen Zhang ◽  
Xiaoxiang Guan ◽  
Neil Kothari ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Adverse Events ◽  
Maintenance Therapy ◽  
Conflicts Of Interest ◽  
Meta Analysis ◽  
Random Effect Model ◽  
Immunomodulatory Drugs ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Grade 3

Abstract Objective: To evaluate the efficacy and safety of immunomodulatory drugs (IMiDs) in maintenance therapy of multiple myeloma through meta-analysis of randomized controlled trials (RCTs). Patients and methods: PubMed, Web of Science, ASCO, ESMO and ASH databases were searched for RCTs that investigated the treatment outcomes (overall survival [OS], progression-free survival [PFS] and/or event-free survival [EFS] and/or time to progression [TTP]) of maintenance therapy with IMiDs in patients with multiple myeloma. Study endpoints included OS, PFS/EFS/TTP, and grade 3 or 4 adverse events. Pooled hazard ratios (HRs) for survival outcomes and risk ratios (RRs) for dichotomous data with 95% confidence interval (CI) were calculated using Comprehensive MetaAnalysis (v2). The random-effect model was utilized in view of clinical heterogeneity in the study population. Results: Eighteen RCTs comprising a total of 6562 patients were included in this meta-analysis. IMiDs used in the RCTs included thalidomide (14 trials) and lenalidomide (4 trials). Overall, IMiD-based maintenance therapy significantly improved OS (HR = 0.91, 95% CI = 0.84 - 0.99, P = 0.027) and PFS (HR = 0.63, 95% CI = 0.60 - 0.68, P < 0.001). Notably, IMiDs maintenance therapy increased OS in the setting of ASCT but showed no OS prolongation without ASCT. On further stratification, thalidomide-based maintenance therapy demonstrated OS benefit only in the setting of ASCT, while lenalidomide-based maintenance therapy did not show OS benefit regardless of transplantation status. For PFS however, both thalidomide- and lenalidomide-based maintenance therapies demonstrated significant survival benefits, regardless of transplantation status (Table 1). IMiD-based maintenance therapy increased the risk of developing grade 3 or 4 neutropenia (RR = 3.04, 95% CI = 2.49 - 3.70, P < 0.001), thrombocytopenia (RR = 2.68, 95% CI = 1.90 - 3.79, P < 0.001), anemia (RR = 1.97, 95% CI = 1.23 - 3.15, P = 0.005), infection (RR = 1.53, 95% CI = 1.22 - 1.92, P < 0.001), fatigue (HR = 1.71, 95% CI = 1.24 - 2.36, P = 0.001), constipation (RR = 2.04, 95% CI = 1.15 - 3.62, P = 0.015), and peripheral neuropathy (RR = 2.02, 95% CI = 1.20 - 3.39, P = 0.008). Conclusions: IMiD-based maintenance therapy results in significant improvement in OS and PFS in multiple myeloma patients but increased the risk of developing some grade 3 or 4 adverse events. While thalidomide-containing maintenance therapy regimens showed OS benefits in the setting of ASCT, lenalidomide-containing maintenance therapy did not prolong OS regardless of transplantation status. Both thalidomide- and lenalidomide-based maintenance therapies increased PFS in multiple myeloma patients independent of transplantation status. When more data on lenalidomide and the newer agent pomalidomide become available, further analysis will be warranted to analyze the efficacy and safety of IMiDs in multiple myeloma maintenance therapy. Table 1. Effects of IMiD-based maintenance therapy on OS and PFS in multiple myeloma patients IMiD ASCT status Survival Number of trials HR 95% CI P value Thalidomide/Lenalidomide combined OS 18 0.91 0.84 - 0.99 0.027 with ASCT OS 10 0.88 0.78 - 0.99 0.036 without ASCT OS 9 0.94 0.83 - 1.06 0.299 Thalidomide combined OS 14 0.92 0.84 - 1.01 0.090 with ASCT OS 8 0.87 0.77 - 1.00 0.049 without ASCT OS 7 0.97 0.85 - 1.10 0.640 Lenalidomide combined OS 4 0.84 0.67 - 1.04 0.102 with ASCT OS 2 0.89 0.66 - 1.20 0.457 without ASCT OS 2 0.78 0.57 - 1.06 0.114 Thalidomide/Lenalidomide combined PFS 17 0.63 0.60 -0.68 < 0.001 with ASCT PFS 9 0.62 0.57 - 0.67 < 0.001 without ASCT PFS 9 0.66 0.60 - 0.73 < 0.001 Thalidomide combined PFS 13 0.67 0.63 - 0.72 < 0.001 with ASCT PFS 7 0.66 0.60 - 0.72 < 0.001 without ASCT PFS 7 0.69 0.62 -0.77 < 0.001 Lenalidomide combined PFS 4 0.50 0.43 - 0.58 < 0.001 with ASCT PFS 2 0.49 0.41 - 0.58 < 0.001 without ASCT PFS 2 0.52 0.40 - 0.67 < 0.001 Disclosures No relevant conflicts of interest to declare.

Efficacy and Safety of Bortezomib Based Regimens Retreatment in Relapsed Multiple Myeloma Patients: Results from a Retrospective Study.

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5387-5387
Author(s):  
Wenjun Wu ◽  
Gaofeng Zheng ◽  
Xiaoyan Han ◽  
Yi Zhao ◽  
Donghua He ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Confidence Interval ◽  
Incidence Rate ◽  
Conflicts Of Interest ◽  
Progression Free Survival ◽  
Initial Therapy ◽  
Efficacy And Safety ◽  
Grade 3 ◽  
Group 1

Abstract Objective: To evaluate the efficacy and safety of bortezomib retreatment in relapsed multiple myeloma (MM) patients, who previously responded to bortezomib. Methods: This retrospective observational study included data from 45 patients and evaluated the efficacy and safety of bortezomib based retreatment in these patients, who had achieved at least a partial response (PR) on initial bortezomib therapy in our hospital from May 2006 to May 2013. Results: The overall response rate (ORR) was 71.2%, among them 9% patients achieved CR, 11.1% patients achieved very good partial response (VGPR), 51.1% patients achieved PR. All patients were divided into 3 groups according to the response of initial bortezomib therapy, including CR group, VGPR group and PR group. After bortezomib retreatment, the ORR of the 3 groups was 76.9%, 75% and 62.5%, respectively. According to the response of bortezomib retreatment, the patients were divided into 2 groups: group 1 who at least achieved PR, group 2 who showed no response. The median progression-free survival (PFS) after bortezomib retreatment for group 1 and 2 was 9( 95% confidence interval 7.947~10.051) and 10 (95% confidence interval 8.381∼11.619) months, respectively (P>0.05), while the median overall survival (OS) after bortezomib retreatment was 71 (95% confidence interval 66.694∼75.306)) and 37 (95% confidence interval 1-28) months, respectively (P<0.05). In patients with bortezomib retreatment had different degrees of adverse events (AE) , the most AE for grade 1~2. The most common grade ≥3 AE was thrombocytopenia, neutropenia and anemia. The incidence rate of grade ≥3 AE peripheral neuropathy bortezomib was 15%. Conclusion: Bortezomib based regimens retreatment was effective and tolerable in relapsed MM patients, who had achieved at least a partial response (PR) on initial therapy. The incidence rate of AE was not significantly increased. Disclosures No relevant conflicts of interest to declare.

scholarly journals Safety and Efficacy Analysis of Selinexor-Based Treatment in Multiple Myeloma, a Meta-Analysis Based on Prospective Clinical Trials

2021 ◽  
Vol 12 ◽  
Author(s):  
Yali Tao ◽  
Hui Zhou ◽  
Ting Niu
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Adverse Events ◽  
Response Rate ◽  
Complete Response Rate ◽  
Meta Analysis ◽  
Complete Response ◽  
Cochrane Central Register ◽  
Safety And Efficacy ◽  
Grade 3

Background: Selinexor (SEL) is an orally bioavailable, highly-selective, and slowly-reversible small molecule that inhibits Exportin 1. Preclinical studies showed that SEL had synergistic antimyeloma activity with glucocorticoids, proteasome inhibitors (PIs) and immunomodulators. The combination of selinexor and dexamethasone (DEX) has been approved in the United States for patients with penta-refractory multiple myeloma in July 2019. This meta-analysis aimed to investigate the safety and efficacy of selinexor based treatment in Multiple myeloma.Methods: We systematically searched the Medline (PubMed), Embase, Web of Science, Cochrane Central Register of Controlled Trials Library databases and ClinicalTrials.gov. Outcome measures of efficacy included overall response rate (ORR), clinical benefit rate (CBR), stringent complete response rate (sCR), complete response rate (CR), very good partial response (VGPR), partial response rate (PR), minimal response (MR), rate of stable disease (SDR), rate of progressive disease (PDR) and median progression-free survival (mPFS). Safety was evaluated by the incidences of all grade adverse events and Grade≥3 adverse events. The subgroup analysis was conducted to analyze the difference in different combination treatment regimens (SEL + DEX + PIs vs SEL + DEX).Results: We included six studies with 477 patients. The pooled ORR, CBR, sCR, CR, VGPR, PR, MR, SDR, and PDR were 43% (18–67%), 55% (32–78%), 5% (−2–13%), 7% (4–11%), 14% (5–24%), 23% (15–31%), 11% (8–14%), 26% (14–38%) and 14% (4–23%), respectively. SEL + DEX + PIs treatment had higher ORR (54 vs 24%, p = 0.01), CBR (66 vs 37%, p = 0.01), sCR (10 vs 2%, p = 0.0008), and VGPR (23 vs 5%, p &lt; 0.00001) compared to SEL + DEX treatment, and lower PDR (4 vs 23%, p &lt; 0.00001) and SDR (17 vs 37%, p = 0.0006). The pooled incidences of any grade and grade≥3 were 45 and 30% in hematological AEs, and in non-hematological AEs were 40 and 30%, respectively. The most common all grade (68%) and grade≥3 (54%) hematological AE were both thrombocytopenia. Fatigue was the most common all grade (62%) and grade≥3 (16%) non-hematological AE. Compared to SEL + DEX treatment, SEL + DEX + PIs treatment had lower incidences of hyponatremia (39 vs 12%, p &lt; 0.00001), nausea (72 vs 52%, p &lt; 0.00001), vomiting (41 vs 23%, p &lt; 0.0001), and weight loss (42 vs 17%, p = 0.03) in all grade AEs. Meanwhile, SEL + DEX + PIs treatment had lower incidences of anemia (36 vs 16%, p = 0.02), fatigue (20 vs 13%, p = 0.04), hyponatremia (22 vs 5%, p &lt; 0.0001) than SEL + DEX treatment in grade≥3 AEs.Conclusion: Our meta-analysis revealed that selinexor-based regimens could offer reasonable efficacy and tolerable adverse events in patients with multiple myeloma. SEL + DEX + PIs treatments had higher efficacy and lower toxicities than SEL + DEX.

scholarly journals Original Versus Generic Lenalidomide in Patients with Relapsed Multipl Myeloma: Comprasion of Effectivity and Adverse Events

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5594-5594
Author(s):  
Zahit Bolaman ◽  
Sehmus Ertop ◽  
Atakan Turgutkaya ◽  
Selim Cem ◽  
Ayse Hilal Eroglu Kucukerdiler ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Adverse Events ◽  
Conflicts Of Interest ◽  
Complete Response ◽  
Muscle Cramp ◽  
P Value ◽  
Medicine Department ◽  
School Of Medicine ◽  
Number Of Patients

Original versus generic lenalidomide in patients with relapsed multipl myeloma: Comprasion of effectivity and adverse events Ali Zahit Bolaman1, Sehmus Ertop2 Atakan Turgutkaya1, Cem Selim, 1 Ayse Hilal Eroglu Kucukerdiler1, Birsen Sahip2, Irfan Yavasoglu1. 1 Adnan Menderes University, School of Medicine, Department of Hematology AYDIN/TURKEY 2 Bulent Ecevit University School of Medicine, Department of Hematology ZONGULDAK/TURKEY Backround: Lenalidomide is an effective IMID derivative drug in the treatment of patients with multiple myeloma. Lenalidomide is available as original and generic forms in our country. So far, there is no any clinical study comparing generic and original lenalidomine for effectivity and adverse events. We compared generic and original lenalidomide effects and adverse events (AEs) in patients with relapsed multiple myeloma (RMM). Methods: The patients with RMM using original or generic lenalidomide were evaluated as retrospectively. Overall response (OR), complete response (CR), very good partial response (VGPR), partial response (PR), stable disease and progressive disease rates and also for adverse events, development rates of neutropenia, anemia, thrombocytopenia, febrile neutropenia, anorexia, constipation diarrhea, nausea, vomiting, creatinine increase, transaminase increase, asthenia, fatigue, pyrexia, peripheral edema, upper respiratory system infection, pneumonia, another infection, muscle cramp, back pain, bone pain, muscle weakness, arthralgia, headache, tremor, paresthesia, deep vein thrombosis, pulmonary embolism, hyperglycemia, hypokalemia, hypocalcemia, hypomagnesaemia, skin dry and skin erythema were investigated in myeloma patients. All data were analyzed using the PASW for Windows version 19.0 (SPSS Inc., Chicago, IL, USA). The results were described as a number, frequency, and percentage. The chi-squared test and Fisher's exact test were used for the analysis of categorical data and independence between variables. The results were assessed at 95% confidence interval and p-value of less than 0.05 was accepted as significant. Results: The number of patients using original lenalidomide was 55 and the number of patients using generic lenalidomide was 43. OR rate was 60 % versus 39.5% in patients using original and generic lenalidomide, respectively. CR rate was 14.5%, VGPR was rate 45.4% in original group while CR rate was 20.9 and VGPR 18.6 in patients using generic lenalidomide. AEs were low in original lenalidomide group than generic group. AEs were usually grade 1 or 2. Response and AEs rates are shown in Table 1. Conclusion: Our study showed original and generic forms of lenalidomide are effective for the treatment of RMM. OR rate was higher in original lenalidomide than generic lenalidomide. The AEs of original lenalidomide were lower than generic lenalidomide without statistically significance. Further studies involving a larger number of patients with RMM would be useful for comparing the efficacy and AEs of original or generic lenalidomide. Disclosures No relevant conflicts of interest to declare.

scholarly journals Carfilzomib-Lenalidomide-Dexamethasone in the Management of Lenalidomide-Refractory Multiple Myeloma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 2-2
Author(s):  
Claudio Cerchione ◽  
Lucio Catalano ◽  
Davide Nappi ◽  
Gerardo Musuraca ◽  
Alessandro Lucchesi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Research Funding ◽  
Primary Prophylaxis ◽  
Cardiac Monitoring ◽  
Salvage Regimen ◽  
Refractory Multiple Myeloma ◽  
Antibiotic Drugs ◽  
Impressive Result ◽  
Significant Efficacy ◽  
Grade 3

Background Carfilzomib is an epoxyketone proteasome inhibitor of second generation, proved to be effective and safe in relapsed and refractory Multiple Myeloma (rrMM), in combination with dexamethasone or lenalidomide and dexamethasone. Aims In this retrospective observational trial, it has been evaluated efficacy and safety of carfilzomib, in combination with lenalidomide-dexamethasone (KRD) as salvage regimen in patients with rrMM, refractory to lenalidomide, where lenalidomide-based regimens have no proven efficacy. Methods 41 patients (23 M/18 F), with rrMM, median age at diagnosis 63.7 years (r. 43-82), median age at start of treatment 67 years (r. 48-84) previously treated with several lines of treatments (median 3, r. 2-11), underwent to KRD regimen (ASPIRE trial schedule) for a median treatment cycles of 8 (r 2-18). ISS was equally distributed, and all patients had previously been treated with bortezomib and IMIDs, and were refractory to this agents. 61% (19/31) of them had undergone at least to a single ASCT. Results According to IMWG criteria, after a median follow-up of 9 months (r. 2-18), ORR was 68,2% (28/41: 9 CR, 12 VGPR, 7 PR) with 5 progressive diseases (PD) and 8 patients in stable disease (SD): this can be considered as an impressive result in this subset of rrMM patients, refractory to lenalidomide. In particular, for 11 patients, KRD was, after having achieved at least a PR, a bridge to second/third autologous SCT. Median time to response was 1.3 months (r.1-4), median OS from diagnosis was 62 months (r. 9-170), median OS from start of Carfilzomib was 11 months (r. 2-18). Carfilzomib was well tolerated, with grade 2 anemia in 39%(16/41) of patients, successfully managed by ESAs, without necessity of blood transfusions; 29% (12/41) grade 3-4 neutropenia (pegfilgrastim in primary prophylaxis was given, no ospedalization was required, no septic shocks were observed); 34% (14/41) grade 2, 21% (9/41) grade 3 and 12% (5/41) grade 4 thrombocytopenia, without hemorrhagic events and transfusion-dependency. Moreover, it was observed pneumonia in 39% (16/41) of patients, treated by common antibiotic drugs and always solved. A cardiac monitoring was performed for all patients: hypertension (grade 2-3) in 34% (14/41) of patients; fatigue in 39% (16/31) of patients. Conclusions Carfilzomib-Lenalidomide-Dexamethasone has shown significant efficacy in a particularly severe setting of patients, relapsed and refractory to all available therapeutic resources, also lenalidomide, and it could be considered as a bridge to a second autologous or allogenic SCT. Disclosures Lucchesi: Incyte: Honoraria; Novartis: Honoraria; Pfizer: Honoraria. Martinelli:Amgen: Consultancy; Celgene: Consultancy, Speakers Bureau; Jazz: Consultancy; Incyte: Consultancy; Pfizer: Consultancy, Research Funding, Speakers Bureau; Roche: Consultancy; Daichii Sankyo: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Janssen: Consultancy.

Anti–B-Cell Maturation Antigen BiTE Molecule AMG 420 Induces Responses in Multiple Myeloma

2020 ◽  
Vol 38 (8) ◽  
pp. 775-783 ◽  
Author(s):  
Max S. Topp ◽  
Johannes Duell ◽  
Gerhard Zugmaier ◽  
Michel Attal ◽  
Philippe Moreau ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
B Cell ◽  
Response Rate ◽  
Human Study ◽  
Cell Maturation ◽  
Refractory Multiple Myeloma ◽  
B Cell Maturation ◽  
Grade 3 ◽  
B Cell Maturation Antigen

PURPOSE The anti–B-cell maturation antigen BiTE molecule AMG 420 was assessed in patients with relapsed/refractory multiple myeloma. PATIENTS AND METHODS In this first-in-human study, up to 10 cycles of AMG 420 were given (4-week infusions/6-week cycles). Patients had progression after ≥ 2 lines of prior therapy and no extramedullary disease. Minimal residual disease (MRD) response was defined as < 1 tumor cell/104 bone marrow cells by flow cytometry. RESULTS Forty-two patients received AMG 420 at 0.2-800 μg/d. Median age was 65 years, and median disease duration was 5.2 years. Median exposure was 1 cycle (range, 1-10 cycles) and 7 cycles (range, 1-10 cycles) for responders. Patients discontinued for disease progression (n = 25), adverse events (AEs; n = 7), death (n = 4), completion of 10 cycles (n = 3), and consent withdrawal (n = 1). Two patients remain on treatment. There were 2 nontreatment-related deaths from AEs, influenza/aspergillosis and adenovirus-related hepatitis. Serious AEs (n = 20; 48%) included infections (n = 14) and polyneuropathy (n = 2); treatment-related serious AEs included 2 grade 3 polyneuropathies and 1 grade 3 edema. There were no grade ≥ 3 CNS toxicities or anti-AMG 420 antibodies. In this study, 800 μg/d was considered to not be tolerable because of 1 instance each of grade 3 cytokine release syndrome and grade 3 polyneuropathy, both of which resolved. The overall response rate was 31% (n = 13 of 42). At the maximum tolerated dose (MTD) of 400 μg/d, the response rate was 70% (n = 7 of 10). Of these, five patients experienced MRD-negative complete responses, and 1 had a partial response, and 1 had a very good partial response; all 7 patients responded during the first cycle, and some responses lasted > 1 year. CONCLUSION In this study of AMG 420 in patients with relapsed/refractory multiple myeloma, the response rate was 70%, including 50% MRD-negative complete responses, at 400 μg/d, the MTD for this study.

Phase II trial of GVDexa (gemcitabine, vinorelbine and dexamethasone) regimen in relapsed/refractory Hodgkin’s lymphoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19519-e19519
Author(s):  
Nikita Mehra ◽  
Prasanth Ganesan ◽  
Jayachandran P K ◽  
Anjana Joel ◽  
Parathan Karunakaran ◽  
...  
Keyword(s):  
Partial Response ◽  
Adverse Events ◽  
Phase Ii ◽  
Hodgkin’S Lymphoma ◽  
Liposomal Doxorubicin ◽  
Objective Response ◽  
Complete Response ◽  
Hodgkin's Lymphoma ◽  
Salvage Regimen ◽  
Grade 3

e19519 Background: Gemcitabine, vinorelbine and liposomal doxorubicin (GVD) is an effective regimen in relapsed/refractory Hodgkin’s lymphoma (RRHL). Conventional second-line chemotherapy is still required as the cost of immunotherapy and antibody-drug conjugates are prohibitive to Indian patients. We report the results of a phase II, open-label, single-arm, single centre interventional study in RRHL where dexamethasone replaced liposomal doxorubicin. Methods: Adult patients (≥18 years) with RRHL at first or second relapse were included. GVDex was delivered as outpatient once in 3 weeks (Gemcitabine 1000 mg/m2 IV over 30 min on D1,8; Vinblastine 25 mg/m2 IV fast infusion on D1,8; Dexamethasone 40 mg PO D1-4) for two cycles followed by interim PET CT assessment by Cheson’s criteria and Deauville scoring. The primary endpoint was the objective response rate (ORR = complete response + partial response). The sample size was calculated using Fleming’s 2-stage model (α error: 0.05 and power: 0.8). Twenty patients were required in the first stage. If there were ≥16 responses, the null hypothesis would be rejected and the study stopped. Results: Between May 2016, and December 2020, 26 patients with RRHL were screened, and 20 were enrolled: primary resistant HL-8 patients (40%) and relapsed HL- 12 patients (60%). The median age was 35 years (range:20-52). Six patients (30%) presented with limited stage and 14 patients (70%) with advanced stage HL at relapse. GVdex was delivered as a first salvage regimen in 18 patients (90%) and second in 2 patients. After 2 cycles of GVDex, 16 (80%) had responded [partial response: 12 (60%); complete response: 4 (20%)]. Median number of cycles of GVDex: 3 (range: 1-4). Five patients (25%) required dose reductions due to chemotherapy-related toxicities. The median duration of objective response was 13.4 months. Eleven patients (55%) underwent high-dose chemotherapy supported by autologous stem cell rescue. After a median follow-up of 25 months (95% CI: 5.9-44.5), the median progression-free survival (PFS) was 24.7 months, and the median overall survival (OS) has not been reached. The estimated 2-year PFS was 44%, and the 2-year OS was 79%. The most common treatment-related adverse events were anemia (100%), neutropenia (70%, 14/20) and fatigue (70%, 14/20). Grade 3 or 4 treatment-related AEs occurred in 14 patients (70%). Grade ≥3 neutropenia occurred in 9 patients (45%) and febrile neutropenia in 3 patients (15%). Serious adverse events were reported in 3 patients (15%). One patient developed Ficat and Arlet classification stage III avascular necrosis of the femoral head. One patient died due to suspected COVID-19 pneumonia (non-neutropenic fever) before cycle 2 of chemotherapy. Conclusions: GVDex it is an effective salvage regimen with acceptable toxicity in patients with RRHL. Clinical trial information: CTRI/2017/04/008361.

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