Updated Report of T-Bird (thalidomide, clarithromycin/[Biaxin®], lenalidomide/[Revlimid®], Dexamethasone) Therapy for Upfront Use In Symptomatic Multiple Myeloma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3050-3050
Author(s):  
Tomer M Mark ◽  
Jennifer O'Loughlin ◽  
Morton Coleman ◽  
David Jayabalan ◽  
Roger N Pearse ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Skin Rash ◽  
Complete Response ◽  
First Line ◽  
Free Survival ◽  
First Line Therapy ◽  
Line Therapy ◽  
Dexamethasone Therapy

Abstract Abstract 3050 Background: We hypothesized that the addition of thalidomide to BiRD therapy (clarithromycin/[Biaxin®], lenalidomide/[Revlimid®], dexamethasone) may improve the anti-myeloma activity of the combination while not adding to overall regimen toxicity, given the different side effect profiles of thalidomide and lenalidomide. We now report an update of the phase 2 trial of T-BiRD (thalidomide/Thalomid®, clarithromycin/[Biaxin®], lenalidomide/[Revlimid®], dexamethasone) therapy for use in up-front treatment of symptomatic multiple myeloma (MM). Methods: Twenty-six patients with newly-diagnosed symptomatic MM were enrolled in a single-institution trial of T-BiRD. The T-BiRD regimen consists of clarithromycin 500mg twice daily, dexamethasone 40mg on days 1,8,15,22 of a 28-day cycle, and lenalidomide 25mg for days 1–21 of a 28-day cycle. Thalidomide is given at a dose of 50mg daily for the first week and thereafter at 100mg daily. All subjects had thromboprophylaxis with aspirin, 162 mg once weekly, 81mg on subsequent days throughout all treatment. Serum protein electrophoresis/immunofixation as well as free light chain determinations were done monthly. Bone marrow biopsy and skeletal imaging were done to confirm disease progression or complete response (CR). Results: Twenty-five patients had completed at least one cycle of T-BiRD and were evaluable. The median number of T-BiRD cycles was 5 (range 1–12). Response to T-BiRD, audited at time of autologous stem cell transplantation (ASCT) or other planned change in therapy, was: 1 (4%) progression of disease (PD), 4 (16%) stable disease (SD), 10 (40%) partial response (PR), 8 (32%) very good PR (VGPR), 1 (4%) complete response (CR), and 1 (4%) with unconfirmed CR, giving a overall response rate (ORR; 3PR) of 80% and a 3VGPR rate of 40%. Nine subjects subsequently underwent ASCT as part of a first line of therapy with T-BiRD induction. These subjects had an ORR of 100% to first-line therapy, with 2 maintaining PR (22%) 5 achieving VGPR (56%), and 2 achieving CR (22%). At three years of follow-up, median progression free survival (PFS) and event free survival (EFS) was not reached for first line therapy (median PFS and EFS censoring at time of ASCT were 65 and 53 weeks, respectively). Median overall survival (OS) was not reached; at 3-year follow-up, 2 patients had died of progressive myeloma, giving an overall survival rate of 92%. A total of 12 subjects (48%) experienced an adverse event (AE), 5 (20%) being study-drug related (RAE). Eight subjects (32%) withdrew from the study: 2 had grade 2 skin rash prior to initiation of full-dose thalidomide (RAE), 1 patient had grade 4 skin rash (Stevens-Johnsons syndrome, SJS) during cycle 1 (RAE), 1 had a TIA in cycle 2, 1 developed renal failure in cycle 1, 1 developed chest pain in cycle 3. Other toxicities include 1 patient with Grade 2 steroid myopathy (RAE), 1 patient with DVT of the leg (RAE), and 1 patient with atrial fibrillation. 2 subjects developed pneumonia (causitive organism not identified). 1 subject died of progressive myeloma prior to completion of 1 cycle. Conclusions: T-BiRD has promising activity as an induction regimen as part of first-line therapy for MM, with prolonged responses; however, toxicity limited extended use. T-BiRD does not appear to be superior to BiRD in ORR, likely due to shorter average time of regimen exposure (median 5 cycles of T-BiRD versus 13 cycles of BiRD). These data continue to support the role of lenalidomide-based regimens in the upfront treatment of MM. Disclosures: Mark: Celgene Corp: Speakers Bureau. Off Label Use: Lenalidomide - upfront use in myeloma. Coleman:Celgene Corp: Speakers Bureau. Zafar:Celgene Corp: Speakers Bureau. Leonard:BiogenIDEC: Consultancy; Genentech: Consultancy; Immunomedics: Consultancy. Niesvizky:Celgene Corp: Consultancy, Speakers Bureau.

scholarly journals Experience of Generic Imatinib As a First Line Therapy for Patients with Chronic Myeloid Leukemia in a Single Reference Institution

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5916-5916
Author(s):  
Gabriel Carvalho Pereira ◽  
Fernanda B da Silva ◽  
Luisa Espirito Santo Oliveira ◽  
Pedro Marques Garibaldi ◽  
Lorena Lobo Figueiredo-Pontes ◽  
...  
Keyword(s):  
Overall Survival ◽  
Adverse Events ◽  
Cytogenetic Response ◽  
Molecular Response ◽  
First Line ◽  
Free Survival ◽  
First Line Therapy ◽  
Line Therapy ◽  
Rate Of Response

Background: The treatment of chronic myeloid leukemia (CML) was revolutionized by the approval of Gleevec (imatinib mesylate) by the FDA in 2001. In low-middle-income countries, due to economic issues related to the high cost of this treatment, scientific governmental entities started to produce and release a generic imatinib in 2013. High quality data about the security profile and efficacy of generic imatinib treatment are still needed. Aims: We herein aimed to evaluate the 6 years follow up of CML patients treated with generic imatinib as first line therapy. Patients and Methods: We evaluated a retrospective cohort of 39 patients diagnosed with CML at a single institution, during the period between December 2001 and July 2019, that had used only generic formulation of imatinib since diagnosis; and analyzed their rate of response to treatment as a primary goal and adverse events and survival outcomes as secondary goals. Responses were evaluated according to ELN 2013. Event-free survival and overall survival were measured from starting date of treatment until: loss of molecular response or death from any cause, and until death from any cause or last seen, respectively. Results: The cohort of 39 patients treated with generic imatinib as first line therapy was composed of 23 men (59%) and 16 women (41%), with median age at diagnosis of 52 years (16-74). The median follow up time was 24 months (8-68), and the median duration of generic imatinib therapy was 19 months (5 - 68). Most of the patients were diagnosed at chronic phase (92%), with only 2 accelerated phase and 1 myeloid blast crisis. Risk stratification according to Eutos, Sokal and Hasford score was low in 92%, 67% and 80%; intermediate in 0%, 30% and 6% and high in 8%, 3% and 14%, respectively. Six different brands of generic imatinib were used (Cristalia, Instituto Vital Brasil, FURP, EMS, Fiocruz and Eurofarma); the most frequently used were Cristalia and Instituto Vital Brasil. The median number of brands used per patient was 2 (1-5). Patients received 400 mg of generic imatinib daily; the dose was increased to 600 mg in 4 patients due to sub-optimal response during follow up. The rate of hematologic response with treatment was 97% and median time to reach it was 1 month (1-7). The rate of response at 3, 6 and 12 months was 74%, 60%, and 92% for optimal cytogenetic response, and 69%, 61%, and 26% for optimal molecular response. The probability to reach deep molecular response at each year of follow up was 41% at 1st year, 52% at 2nd year, 46% at 3rd year, 50% at 4th year, 50% at 5th year, and 50% at 6th year. The probability to reach a molecular response 4.5 at each year of follow up was 10% at 1st year, 23% at 2nd year, 30% at 3rd year, 50% at 4th year, 50% at 5th year, and 50% at 6th year. Hematologic toxicities were frequent during the first three months of therapy. Reported non-hematologic adverse events were hypophosphatemia (62%), diarrhea (30%), cramps (30%), liver toxicity (28%), nausea (18%), bone pain (18%), edema (15%), rash (8%), and hypomagnesaemia (2.5%). Eight percent of patients evolved with deterioration of renal function during the treatment period, but its relationship with generic imatinib was not well established. Two patients (5%) needed a dose reduction because of adverse events. Eight (20.5%) patients switched to second line tyrosine-kinase inhibitors, five (13%) due to resistance and three (8%) due to side effects (severe hepatotoxicity, diarrhea, and rash). Three patients progressed after switching to another tyrosine kinase inhibitor. After a median follow up of 24 months, the event free survival rate was 80% and the overall survival rate was 100%. Conclusion: The rate of complete cytogenetic response, resistance, and intolerance after use of generic imatinib was not worse than the rates described in the long-term follow up of the IRIS trial (N Engl J Med 2017; 376:917-927). Deep molecular response rates seen in the cohort of patients on generic imatinib were inferior to the ones in the IRIS trial, but overall survival was not impacted. Hypophosphatemia was observed in a high percentage of patients, although it has not been reported in other cohorts on generic imatinib. Prospective randomized studies are needed to allow better conclusions regarding the comparative efficacy and safety of generic imatinib. Disclosures Figueiredo-Pontes: Novartis: Honoraria.

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.

Prognostic impact of prior local therapy in castration-resistant prostate cancer

2021 ◽  
Author(s):  
Mikifumi Koura ◽  
Masaki Shiota ◽  
Shohei Ueda ◽  
Takashi Matsumoto ◽  
Satoshi Kobayashi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Local Therapy ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Free Survival ◽  
First Line Therapy ◽  
Castration Resistant ◽  
Line Therapy

Abstract Objective This study aimed to reveal the prognostic values of prior local therapy in first-line therapy using androgen receptor-axis targeting agents (abiraterone or enzalutamide) or docetaxel for castration-resistant prostate cancer (CRPC). Methods The study included 303 patients treated with first-line therapy for non-metastatic and metastatic CRPC. The association between prior local therapy and therapeutic outcome including progression-free survival and overall survival was investigated by univariate and multivariate analyses as well as propensity score-matched analysis. Results In univariate analysis, local prior therapy was associated with a lower risk of all-cause mortality (hazard ratio, 0.56, 95% confidence interval, 0.40–0.79; P = 0.0009). Overall survival, but not progression-free survival, was better among patients with prior local therapy compared with patients without prior local therapy even after multivariate analysis and propensity score-matched analysis. Conclusions This study robustly indicated that prior local treatment was prognostic for overall survival among patients with CRPC. This finding is useful to predict patient prognosis in CRPC.

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

Patterns of Disease Relapse and Progression in Patients with Multiple Myeloma After First Line Therapy with Autologous Stem Cell Transplantation: Implications for Patient Monitoring After Transplantation

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 825-825
Author(s):  
Dmitriy Zamarin ◽  
Manisha Bhutani ◽  
Danielle Chimento ◽  
Sergio Giralt ◽  
Nikoletta Lendvai ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Soft Tissue ◽  
First Line ◽  
Post Transplant ◽  
First Line Therapy ◽  
Line Therapy ◽  
Group A ◽  
One Year ◽  
Group B

Abstract Abstract 825 BACKGROUND: Autologous stem cell transplantation (ASCT) is a widely used therapeutic option in first line treatment of multiple myeloma (MM). However, many patients eventually relapse. While precise knowledge of relapse and progression (R/PD) patterns would be important to generate evidence based surveillance recommendations after ASCT, such data is limited in the literature, especially in the era following the introduction of the free light chain assay. The purpose of this study is to examine the patterns of post-ASCT relapse and to derive evidence based recommendations for optimal surveillance of patients. METHODS: We performed a retrospective analysis on 258 patients with MM who underwent ASCT within one year of diagnosis at MSKCC between 2000 and 2010, as part of first line therapy. We used the IMWG standard criteria for serologic and clinical R/PD. We first determined for all patients the date of serologic R/PD. Patients identified as having serologic R/PD were further examined to determine whether clinical (anemia, renal failure, hypercalcemia, development of soft tissue lesions), radiologic (skeletal survey) or urinary R/PD had anteceded serologic R/PD. Several groups of patients were derived and further analyzed in terms of relapse patterns and adequacy of follow up. RESULTS: Among 258 patients, 173 were determined to have serologic R/PD at a median of 19.2 months post-transplant. Among these patients, on the dates of their serologic R/PD, 17 (9.8%) had concurrent overt symptomatic evidence of clinical/radiologic R/PD (Group A symptomatic R/PD), while 156 (90.2%) were found to have isolated asymptomatic serologic R/PD without apparent evidence of concomitant clinical/radiologic R/PD (Group B asymptomatic R/PD). Group A included patients with distinct and sometimes coinciding clinical characteristics (poor risk cytogenetics with aggressive disease (n=3), leptomeningeal relapse (n=1), soft tissue relapse (n=4) and acute severe anemia at relapse (n=3)); patients with IgA gammopathy (n=5); and patients considered to have inadequate serologic follow up intervals (range of follow up interval between date of serologic R/PD and prior serologic testing 149 to 245 days) (n=6). Upon further examination of group B, 44 patients had radiologic imaging at the time of serologic R/PD (within 4 weeks following the date of serologic R/PD). Fourteen among them (32%) had evidence of new bone lesions. Among all 173 patients with serologic R/PD, 83 patients had a skeletal survey within one year prior to the date of serologic R/PD. Only 3 (3.6%) had evidence of radiologic R/PD anteceding serologic R/PD. All 3 patients were considered to have had inadequate serologic follow up interval (Range 208 to 252 days). Abnormal urine immunofixation (UIF) anteceded serologic R/PD in 5 out of 41 (12%) patients tested who had achieved CR post transplant. In these patients the abnormal UIF anteceded the serologic R/PD by a mean of 2.4 months. Abnormal UPEP anteceded serologic R/PD by 1.9 months in only 1 out of 40 (2.5%) patients tested who had achieved less than CR post transplant. CONCLUSIONS: Based on the results of this analysis, several conclusions can be drawn: 1) The vast majority of R/PD in patients with MM are asymptomatic R/PD detected first by serologic studies. A small percentage of patients (those with aggressive cytogenetics, specific relapse types including soft tissue, severe cytopenia, and IgA gammopathy) will have symptomatic R/PD with overt concomitant evidence of clinical and/or radiologic R/PD at the time of serologic R/PD; 2) Among patients who have apparent asymptomatic R/PD, a significant percentage will have evidence of skeletal lesions and therefore imaging should be recommended in these patients; 3) In the absence of serological R/PD, routine surveillance screening with yearly skeletal surveys cannot be recommended based on this analysis since this test was not useful in any of the analyzable patients in whom it was obtained; 4) Aside from few patients in CR whose relapse may be detected earlier by UIF (with probably no clinical benefit), all patients with multiple myeloma whose disease progresses will have serologic R/PD at the time of progression and follow up limited to serologic testing may well be sufficient for monitoring patients with MM post transplant. Disclosures: No relevant conflicts of interest to declare.

The Ki67/CD138 Ratio Independently Predicts Overall Survival in the Upfront Treatment of Newly Diagnosed Multiple Myeloma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2016-2016
Author(s):  
Tomer M Mark ◽  
Peter Forsberg ◽  
Ihsane Ouansafi ◽  
Adriana C Rossi ◽  
Roger N Pearse ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Overall Survival ◽  
Board Of Directors ◽  
Research Funding ◽  
Complete Response ◽  
Newly Diagnosed ◽  
First Line ◽  
Advisory Committees ◽  
Line Therapy

Abstract Background: Assessment of malignant plasma cell cycling via plasma cell labeling index (PCLI) has been a validated prognostic tool in multiple myeloma (MM) but the test requires specialized technical expertise and is not widely available. Ki67 is a well-known protein marker of cellular proliferation on immunohistochemical (IHC) staining with prognostic utility in other malignancies. In an effort to develop a simpler system to provide analogous information to PCLI, we used a novel IHC co-staining technique for CD138 and Ki67 to quantify plasma cells in active cycling. We then performed a retrospective analysis of the ratio of Ki67/CD138 (Ki67%) in newly diagnosed patients with multiple myeloma receiving 1st-line therapy to correlate with clinical outcomes. Methods: A retrospective cohort study of patients (pts) with treated symptomatic MM was performed by interrogation of the clinical database at the Weill Cornell Medical College / New York Presbyterian Hospital. For inclusion in the analysis, subjects must have started first-line treatment in the period of 2005-2010, and had available bone marrow biopsies. Double-staining with Ki67 and CD138 was performed by IHC. The Ki67% was calculated as the percent of plasma cells expressing CD138 that were also found to express Ki67. Treatment outcomes were stratified and compared based on %Ki67. Response was determined by monthly serum protein electrophoresis / immunofixation (IFX) with free light chain analysis according to International Multiple Myeloma Working Group (IMWG) guidelines. Pts who were IFX negative but had no subsequent bone marrow biopsy were classified as being in unconfirmed complete remission. Results: We identified 151 patients with newly diagnosed MM and available %Ki67 expression who received first-line therapy over the period of 2005-2010. Patient were subdivided into two groups based on %Ki67: Low: %ki67 <= 5%, n = 87; and High: %Ki67 >5, n=64, to allow for comparison of treatment response and survival analysis. Specific therapeutic agent exposure history did not differ significantly between patients. Both groups had similar depth of response rates (ORR) to front-line therapy, Table 1. Median progression-free survival for the high versus low %Ki67 groups approached statistical significance at 54 months (95% CI 30.8,67.4) versus 26.9 months (95% CI 21.6,40.2), respectively (P = 0.083). At data cut-off, there were 30 deaths in the low %Ki67 group (1-yr OS 93%, 5-yr OS 71%) and 36 deaths in the high %Ki67 group (1-yr OS 94%, 5-yr OS 62%). Median overall survival (OS) was not reached for Ki67% <= 5% (95% CI 97.3,NR) vs. 78.9 months (95% CI 55.9,93.1) for Ki67% > 5%, (P = 0.0434), Figure 1. Multivariate cox regression for factors with influence on OS showed that only high-risk cytogenetics (HR 2.05, 95% CI 1.17, 2.92, P = 0.027), ISS (HR 1.835, 95% CI 1.33, 3.60, P = 0.000), and %Ki67 group status had an independent effect on survival outcome. Low (<=5%) versus high (>5%) %Ki67 influenced overall survival with a hazard ratio of 1.76 (CI 1.07,2.92, P = 0.027). Survival after ASCT was significantly longer in the low %Ki67 group with median OS not reached (95%CI, 97.3, NR) versus 86.9 months (95% CI 43.9, NR) for high %Ki67 group (P = 0.04). Discussion: The ratio of IHC double positive Ki67 and CD138 of > 5% is an independent prognostic marker for overall survival in newly diagnosed MM undergoing 1st line therapy. The %Ki67 serves as a simpler and widely available analog to PCLI that can be presently performed in most hematopathology laboratories. Table 1: First Line Treatment and Best Response (modified IMWG Criteria) Ki67% <= 5(N = 87)n (%) Ki67% > 5(N = 64)n (%) P Treatment Exposure* Lenalidomide 59 (67.8) 48 (75) 0.34 Thalidomide 30 (34.5) 14 (21.9) 0.09 Bortezomib 25 (28.7) 14 (21.9) 0.34 Alkylating agent 11 (12.6) 4 (6.3) 0.19 ASCT 27 (31) 22 (34.4) 0.66 Best Response Overall Response (>= Partial response) 77 (88.4) 57 (89.1) 0.41 Complete response 15 (17.2) 22 (34.4) Unconfirmed complete response** 14 (16.1) 8 (12.5) Very good partial response 23 (26.4) 15 (23.4) Partial response 25 (28.7) 12 (18.8) Stable disease 9 (10.3) 5 (7.8) Progressive disease 1 (1.2) 2 (3.1) * Percentages do not add to 100% due to instances of concurrent therapy use ** Unconfirmed complete response: immunofixation negative, but no confirmatory bone marrow biopsy available Figure 1 Overall Survival by %Ki67 Figure 1. Overall Survival by %Ki67 Disclosures Mark: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millennium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Onyx: Research Funding, Speakers Bureau. Rossi:Celgene: Speakers Bureau. Pekle:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Millennium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Perry:Celgene: Speakers Bureau. Coleman:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Millennium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Onyx: Honoraria. Niesvizky:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millennium: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Onyx: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Patient Outcomes with Proteosome Inhibitor Bortezomib in Multiple Myeloma at an English District General Hospital

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5745-5745
Author(s):  
Anil Vaikunth Kamat ◽  
Tariq Shafi ◽  
Raphael A. Ezekwesili
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Progression Free Survival ◽  
Second Primary ◽  
Second Line ◽  
First Line ◽  
Free Survival ◽  
Grade 3 ◽  
Second Primary Malignancies

Abstract Bortezomib is a targeted proteosome inhibitor licensed & approved for in multiple myeloma both as first line and in relapsed setting. This is a retrospective non experimental cross sectional quantitative comparative group study using clinical case notes, laboratory & pharmacy records for patients treated with Bortezomib in 2011 & 2012. Outcomes studied included remission status, adverse events, progression free survival and overall survival at follow up. The study also looked at the comparative responses of cohort of patients administered Bortezomib through intravenous & subcutaneous route. The cohort consisted of 33 patients, 21 male, 11 female, median age 71 years, first line 10 patients, second line 23 , median number of cycles in 2011 & 2012 – first line 3 & 8 , second line 5 & 4, respectively. In 2011, 8 received intravenous treatment, 9 were switched from intravenous to subcutaneous route whilst all patients from 2012 received subcutaneous Bortezomib. The most frequently used regimen was Bortezomib Dexamethasone ( VD). The overall response rate ( ORR >/= Minor Response) was: First line 70% (7/10) ; Second line 47.8% ( 11/23); median PFS ( Figure 1) 6 months ( First line: 7 months ; Second line : 6 months) and median overall survival ( Figure 2) at follow up: 9 months ; 39.4 % ( 13/33) First line 8.5 months, Second line 11 months. Subcutaneous Bortezomib was equivalent to intravenous Bortezomib in terms of efficacy & tolerance. Of 33 patients, there were 12 dose reductions. Adverse events reported included: peripheral Neuropathy - grade 3 - 6% ( all grades 27.3%); Diarrhoea - grade 3 - 3% (all grades 6%); Nausea / Vomiting - grade 3 - 3% ( all grades 6%) and Second Primary Malignancies - 12% ( 4 of 33). Mortality at follow up was 20 patients from cohort of 33 ; causes included disease progression in 11, second primary malignancy with disease progression in 4, COPD 2, Systemic Amyloidosis 2, Tuberculosis 1 , Multiple co morbidities 1 and Asthma with mechanical failure in single patient. Second primary malignancies ( 4/33) included Prostate carcinoma ( 1), Renal Cell Carcinoma (1), Neuroendocrine tumour ( 1 ) and Unknown Primary in single patient. Beyond second line treatment, majority (14 of 23 patients; 60.9 %) did not have further active treatment. These data indicate that patient outcomes were modest compared to published data from VISTA and APEX trials. Majority of patients did not have further active treatment beyond second line which suggests the most effective treatment strategy should be used upfront as patients may not be fit to have further lines of therapy despite availability of recently introduced novel targeted agents. A higher percentage of second primary malignancies were noticed in this cohort which should be an area of further clinical research. Figure 1: Progression free survival with Bortezomib as first line & second line in multiple myeloma Figure 1:. Progression free survival with Bortezomib as first line & second line in multiple myeloma Figure 2: Overall survival with Bortezomib as first line & second line in multiple myeloma Figure 2:. Overall survival with Bortezomib as first line & second line in multiple myeloma Disclosures No relevant conflicts of interest to declare.

Bortezomib-Melphalan-Prednisone-Thalidomide Followed by Maintenance With Bortezomib-Thalidomide Compared With Bortezomib-Melphalan-Prednisone for Initial Treatment of Multiple Myeloma: Updated Follow-Up and Improved Survival

2014 ◽  
Vol 32 (7) ◽  
pp. 634-640 ◽  
Author(s):  
Antonio Palumbo ◽  
Sara Bringhen ◽  
Alessandra Larocca ◽  
Davide Rossi ◽  
Francesco Di Raimondo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Response Rate ◽  
Complete Response Rate ◽  
Progression Free Survival ◽  
Complete Response ◽  
Free Survival ◽  
Grade 3 ◽  
To Receive

Purpose Bortezomib-melphalan-prednisone (VMP) has improved overall survival in multiple myeloma. This randomized trial compared VMP plus thalidomide (VMPT) induction followed by bortezomib-thalidomide maintenance (VMPT-VT) with VMP in patients with newly diagnosed multiple myeloma. Patients and Methods We randomly assigned 511 patients who were not eligible for transplantation to receive VMPT-VT (nine 5-week cycles of VMPT followed by 2 years of VT maintenance) or VMP (nine 5-week cycles without maintenance). Results In the initial analysis with a median follow-up of 23 months, VMPT-VT improved complete response rate from 24% to 38% and 3-year progression-free-survival (PFS) from 41% to 56% compared with VMP. In this analysis, median follow-up was 54 months. The median PFS was significantly longer with VMPT-VT (35.3 months) than with VMP (24.8 months; hazard ratio [HR], 0.58; P < .001). The time to next therapy was 46.6 months in the VMPT-VT group and 27.8 months in the VMP group (HR, 0.52; P < .001). The 5-year overall survival (OS) was greater with VMPT-VT (61%) than with VMP (51%; HR, 0.70; P = .01). Survival from relapse was identical in both groups (HR, 0.92; P = .63). In the VMPT-VT group, the most frequent grade 3 to 4 adverse events included neutropenia (38%), thrombocytopenia (22%), peripheral neuropathy (11%), and cardiologic events (11%). All of these, except for thrombocytopenia, were significantly more frequent in the VMPT-VT patients. Conclusion Bortezomib and thalidomide significantly improved OS in multiple myeloma patients not eligible for transplantation.

scholarly journals Effectiveness of Afatinib and Gefitinib in Non-Small Cell Lung Cancer (NSCLC) Epidermal Growth Factor Receptor (EGFR) Mutations in Indonesia: Observational Studies with Retrospectives

2019 ◽  
Vol 10 (4) ◽  
pp. 3516-3522
Author(s):  
Seftika Sari ◽  
Tri Murti Andayani ◽  
Dwi Endarti ◽  
Kartika Widayati
Keyword(s):  
Overall Survival ◽  
Clinical Practice ◽  
Medical Records ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
First Line ◽  
Free Survival ◽  
First Line Therapy ◽  
Line Therapy ◽  
Nsclc Patients

Effectiveness data can describe the results or performance of an intervention (treatment) in daily clinical practice and also provide recommendations to policymakers regarding the need or not of health technology to be implemented into the health care system. Research related to the effectiveness of afatinib and gefitinib is still minimal, especially in Indonesia. This study aims to provide an overview of the effectiveness of afatinib and gefitinib in daily clinical practice (the real world) as first-line therapy. This research is an observational study with a retrospective approach that observes the medical records of NSCLC patients who have EGFR mutations in Dr. Sardjito General Hospital Yogyakarta and Dr. Kariadi General Hospital Semarang, Java Island, Indonesia in the period January 2016 - March 2019. The effectiveness seen is the Progress Free Survival and Overall Survival based on the patient's medical records and analyzed using the Kaplan Meier test to see survival. There were 113 patients identified, 27 patients using afatinib and 86 patients using gefitinib. Afatinib had significantly superior progression-free survival (448 days or 14.7 months; 95% CI = 12-17.4 months; p = 0.002) compared to gefitinib (344 days or 11.3 months; 95% CI = 8, 4-14.3 months), however, overall survival of afatinib is no better than gefitinib (472 days or 15.5 months; 95% CI = 13.8-17.2 months vs 653 days or 21.4 months; 95% CI = 18-24.8 months) with a value of p = 0.302. Afatinib has superior progression-free survival compared to gefitinib, but not overall survival as first-line therapy in NSCLC patients with EGFR mutations.

Prognostic value of incidental betablockers use in metastatic colorectal cancer patients receiving first-line treatment.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14610-e14610
Author(s):  
Michela Del Prete ◽  
Riccardo Giampieri ◽  
Mario Scartozzi ◽  
Elena Maccaroni ◽  
Luca Faloppi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Response Rate ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
First Line Therapy ◽  
Line Therapy ◽  
Colorectal Cancer Patients

e14610 Background: Preclinical and retrospective studies suggested antitumor activity for the incidental use of betablockers in various tumour types. Data regarding colorectal cancer are lacking. We assessed the correlation between the incidental use of betablockers and clinical outcome in colorectal cancer patients receiving first-line therapy. Methods: 235 patients treated with first-line chemotherapy alone (128 patients) and with Bevacizumab (107 patients) were analysed. Patients were stratified for betablockers use, age, sex, site of metastases, previous adjuvant chemotherapy and ECOG performance status. Results: 29 patients (12%) were on treatment with betablockers at the time of first-line therapy: 20 (16%) in the chemotherapy alone group and 9 in the bevacizumab group (8%). In both groups patients receiving or not betablockers were similar for all main clinical characteristics. In the chemotherapy alone group, patients receiving betablockers showed an improved response rate (60% vs. 33%, p=0.044) and overall survival (mOS 41.3 vs 25.7 months, p=0.03, HR:2.26, 95% CI: 1.05-3.24). Only a trend for improved progression free survival was noticed. In the 107 patients receiving chemotherapy with bevacizumab a trend towards a worse overall survival was seen for patients receiving betablockers, although this was not statistically significant (mOS 16 vs 23.7 months, p=0.26, HR:0.64, 95% CI: 0.22-1.49). No significant differences were seen in regards of progression free survival or different response rate patterns between the two groups. Conclusions: Our analysis confirms a potential prognostic role for the use of betablockers in colorectal cancer patients treated with chemotherapy. Our findings are in line with preclinical studies suggesting that beta-adrenergic signalling may regulate cancerogenesis and tumor invasiveness. Our analysis suggests a potential worse outcome for patients on betablockers receiving Bevacizumab-based treatment, although the small number of patients precludes any definitive conclusion. We suggest that in future prospective trials the incidental use of betablockers will be considered a stratification factor for clinical outcome.

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