scholarly journals Effect of Obesity on the Efficacy and Toxicities in Patients Undergoing Autologous Hematopoietic Stem Cell Transplant (AHCT) for Lymphoma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4617-4617
Author(s):  
Nicole Pearl ◽  
Andrew Lin ◽  
Patrick Hilden ◽  
Larry W Buie ◽  
Kevin Robinson ◽  
...  
Keyword(s):  
Overall Survival ◽  
Body Weight ◽  
Progression Free Survival ◽  
Patient Characteristics ◽  
Obese Group ◽  
Obese Patients ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Baseline Characteristics ◽  
Grade 3

Abstract Background - Increased patient obesity rates have brought into question the need for dose adjustments in chemotherapy. Strategies for dose adjustments include using adjusted body weight (adjBW) versus total body weight (TBW) (Fair, 2017). Incorrect dosing of chemotherapy can result in significant complications. Underdosing has the potential to lead to treatment failure, whereas overdosing can result in increased toxicity. Currently, there is a lack of data regarding appropriate dose adjustments for conditioning chemotherapy regimens in patients with lymphoma who undergo autologous hematopoietic stem cell transplantation (AHCT) (Fair, 2017; Bubalo, 2014). Objective - The primary objective of this study is to evaluate the effect of obesity on overall survival (OS) in lymphoma patients who have undergone AHCT. The secondary objectives are to evaluate progression-free survival (PFS), as well as safety and toxicity (particularly gastrointestinal, renal and liver toxicities, and infections). Methods - Patients with lymphoma who received an AHCT were identified from our institutional database. Baseline patient characteristics and dose adjustments to conditioning chemotherapy regimens made in the setting of obesity were collected. Obesity was defined as actual body weight that is ≥ 125% Ideal Body Weight (IBW) as per Memorial Sloan Kettering Cancer Center allogeneic/autologous hematopoietic cell transplantation chemotherapy guidelines. Transplant outcomes (OS and PFS) and toxicities were compared between non-obese and obese patients. Sub-group analysis of the obese patient population compared those who received conditioning regimens based on adjBW versus TBW. Survival outcomes were estimated using the Kaplan-Meier method with differences assessed using a log-rank test. Differences in toxicity rates were assessed using a chi-square or fisher's exact test as appropriate. Results - The 239 patients transplanted between January 2014 and August 2016 had a median age of 55.3 (range 19.1 - 77.1) and 44.8% were female. Their median Body Mass Index was 27.3 kg/m2 (range 16.8 - 53.2). Baseline characteristics of patients are summarized in Table 1, and the subset of obese patient characteristics are summarized in Table 2. Of the obese patients (N=110, 46.0%), 29.1% received chemotherapy based on adjBW. PFS and OS did not differ significantly between the non-obese group and the obese group (3-year PFS - 69.8% vs. 74.3%, P=0.25; 3-year OS - 85.7% vs. 89.7%, P=0.42). The median follow-up of surviving patients was 36.1 months. Within the obese group, PFS and OS were significantly longer in the group that received conditioning chemotherapy dosed on TBW than adjBW (3-year PFS - 84.3% vs. 49.9%, P<0.001; 3-year OS - 97.0% vs. 71.9%, P<0.001). Toxicities were graded according to the NCI Common Technology Criteria for Adverse Effects v4.0 (CTCAE). Most toxicity outcomes were similar between the non-obese and obese groups. The rate of grade 3 or 4 liver toxicity was significantly higher in the non-obese group than the obese group (5.4% vs. 0%, P=0.02). In the obese group, there were no reported grade 3 or 4 renal toxicities. No significant differences were observed between the TBW and adjBW groups for grade 3 or 4 infections (89.7% vs. 78.1%, P=0.13) or gastrointestinal toxicities (56.4% vs. 34.4%, P=0.06), potentially related to sample size. Multivariate analyses controlling for significant between-group differences in baseline characteristics are pending. Conclusion - Among obese adults with lymphoma undergoing an AHCT, conditioning chemotherapy dosed on TBW was associated with longer overall survival and progression-free survival than chemotherapy dosed on adjBW, without increased rates of toxicities. Disclosures No relevant conflicts of interest to declare.

scholarly journals Histological Impact on Follicular Lymphoma Grade 3 Treated With Frontline RCHOP Regimen

2021 ◽  
Author(s):  
Feifei Chen ◽  
Aziguli Maihemaiti ◽  
Zheng Wei ◽  
Luya Cheng ◽  
Weiguang Wang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Follicular Lymphoma ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Baseline Characteristics ◽  
Grade 3 ◽  
Large B Cell

Abstract Background Histologically, follicular lymphoma (FL) grade 3 is subdivided into grade 3A and 3B. However, there are limited studies on outcomes of FL grade 3A and 3B treated with frontline of RCHOP treatment. Methods We retrospectively analyzed 61 patients of FL grade 3 treated with frontline RCHOP regimen between January 2009 and December 2019. We divided them into FL grade 3A (n = 42) and aggressive FL (n = 19). Aggressive FL included grade 3A with an additional 3B component (n = 2), grade 3B (n = 8), and grade 3 with areas of diffuse large B cell lymphoma (n = 9). Results The baseline characteristics were similar between FL grade 3A and aggressive FL. The 3-year overall survival (OS) was 97.1% in FL grade 3A and 81.9% in aggressive FL (P = 0.041). The 3-year progression free survival (PFS) was not significantly different between two groups, with 69.1% and 71.1%, respectively (P = 0.546). However, patients of aggressive FL reached a plateau in the PFS curve after 2 years. Conclusions Compared with patients of aggressive FL, FL grade 3A patients presented an uncurable feature but associated with a better OS with frontline RCHOP treatment.

scholarly journals Evaluation of efficacy and toxicity of nivolumab combined with or without docetaxel in patients with advanced NSCLC

2021 ◽  
Author(s):  
Yang Wang ◽  
Jun Nie ◽  
Ling Dai ◽  
Weiheng Hu ◽  
Jie Zhang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Advanced Nsclc ◽  
Objective Response ◽  
Progression Free Survival ◽  
Meaningful Improvement ◽  
Free Survival ◽  
Significant Difference ◽  
Grade 3 ◽  
Doublet Chemotherapy ◽  
Platinum Doublet

Abstract Background The combination of PD-1/PD-L1 inhibitor and chemotherapy has been clinically confirmed to be beneficial as the first-line treatment of patients with advanced NSCLC. This study aimed to assess the effect of nivolumab + docetaxel versus nivolumab monotherapy in patients with NSCLC after the failure of platinum doublet chemotherapy. Materials and methods The efficacy and toxicity of nivolumab + docetaxel combination therapy versus nivolumab monotherapy were compared in this retrospective study. Primary endpoint of the study was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), overall survival (OS), and toxicity. Results Between November 2017 and December 2019, 77 patients were included in this study, with 58 patients in the nivolumab group and 19 in the nivolumab + docetaxel group. The median follow-up was 18 months, and the PFS was 8 months for patients receiving nivolumab + docetaxel and 2 months for those receiving nivolumab alone (p = 0.001), respectively. Nivolumab + docetaxel showed superior OS compared with nivolumab, with the median OS unreached versus 7 months (p = 0.011). Among patients without EGFR/ALK variation, compared to nivolumab monotherapy, nivolumab + docetaxel showed better PFS (p = 0.04) and OS (p  = 0.05). There was no significant difference in grade 3–4 adverse events (AEs) between the two groups (p = 0.253). Conclusions The combination of nivolumab and docetaxel demonstrated a meaningful improvement in progression-free survival and overall survival compared to nivolumab monotherapy, in patients with NSCLC after the failure of platinum doublet chemotherapy, irrespective of EGFR/ALK variation status.

Phase III Trial of Epirubicin Plus Paclitaxel Compared With Epirubicin Plus Cyclophosphamide As First-Line Chemotherapy for Metastatic Breast Cancer: United Kingdom National Cancer Research Institute Trial AB01

2005 ◽  
Vol 23 (33) ◽  
pp. 8322-8330 ◽  
Author(s):  
Ruth E. Langley ◽  
James Carmichael ◽  
Alison L. Jones ◽  
David A. Cameron ◽  
Wendi Qian ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Survival Time ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
Grade 3 ◽  
Line Chemotherapy

Purpose To compare the effectiveness and tolerability of epirubicin and paclitaxel (EP) with epirubicin and cyclophosphamide (EC) as first-line chemotherapy for metastatic breast cancer (MBC). Patients and Methods Patients previously untreated with chemotherapy (except for adjuvant therapy) were randomly assigned to receive either EP (epirubicin 75 mg/m2 and paclitaxel 200 mg/m2) or EC (epirubicin 75 mg/m2 and cyclophosphamide 600 mg/m2) administered intravenously every 3 weeks for a maximum of six cycles. The primary outcome was progression-free survival; secondary outcome measures were overall survival, response rates, and toxicity. Results Between 1996 and 1999, 705 patients (353 EP patients and 352 EC patients) underwent random assignment. Patient characteristics were well matched between the two groups, and 71% of patients received six cycles of treatment. Objective response rates were 65% for the EP group and 55% for the EC group (P = .015). At the time of analysis, 641 patients (91%) had died. Median progression-free survival time was 7.0 months for the EP group and 7.1 months for the EC group (hazard ratio = 1.07; 95% CI, 0.92 to 1.24; P = .41), and median overall survival time was 13 months for the EP group and 14 months for the EC group (hazard ratio = 1.02; 95% CI, 0.87 to 1.19; P = .8). EP patients, compared with EC patients, had more grade 3 and 4 mucositis (6% v 2%, respectively; P = .0006) and grade 3 and 4 neurotoxicity (5% v 1%, respectively; P < .0001). Conclusion In terms of progression-free survival and overall survival, there was no evidence of a difference between EP and EC. The data demonstrate no additional advantage to using EP instead of EC as first-line chemotherapy for MBC in taxane-naïve patients.

scholarly journals Melflufen and Dexamethasone in Heavily Pretreated Relapsed and Refractory Multiple Myeloma

2020 ◽  
pp. JCO.20.02259
Author(s):  
Paul G. Richardson ◽  
Albert Oriol ◽  
Alessandra Larocca ◽  
Joan Bladé ◽  
Michele Cavo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Overall Response Rate ◽  
Response Rate ◽  
Progression Free Survival ◽  
Free Survival ◽  
Duration Of Response ◽  
Heavily Pretreated ◽  
Grade 3

PURPOSE Melphalan flufenamide (melflufen) is a first-in-class peptide-drug conjugate that targets aminopeptidases and rapidly and selectively releases alkylating agents into tumor cells. The phase II HORIZON trial evaluated the efficacy of melflufen plus dexamethasone in relapsed and refractory multiple myeloma (RRMM), a population with an important unmet medical need. PATIENTS AND METHODS Patients with RRMM refractory to pomalidomide and/or an anti-CD38 monoclonal antibody received melflufen 40 mg intravenously on day 1 of each 28-day cycle plus once weekly oral dexamethasone at a dose of 40 mg (20 mg in patients older than 75 years). The primary end point was overall response rate (partial response or better) assessed by the investigator and confirmed by independent review. Secondary end points included duration of response, progression-free survival, overall survival, and safety. The primary analysis is complete with long-term follow-up ongoing. RESULTS Of 157 patients (median age 65 years; median five prior lines of therapy) enrolled and treated, 119 patients (76%) had triple-class–refractory disease, 55 (35%) had extramedullary disease, and 92 (59%) were refractory to previous alkylator therapy. The overall response rate was 29% in the all-treated population, with 26% in the triple-class–refractory population. In the all-treated population, median duration of response was 5.5 months, median progression-free survival was 4.2 months, and median overall survival was 11.6 months at a median follow-up of 14 months. Grade ≥ 3 treatment-emergent adverse events occurred in 96% of patients, most commonly neutropenia (79%), thrombocytopenia (76%), and anemia (43%). Pneumonia (10%) was the most common grade 3/4 nonhematologic event. Thrombocytopenia and bleeding (both grade 3/4 but fully reversible) occurred concomitantly in four patients. GI events, reported in 97 patients (62%), were predominantly grade 1/2 (93%); none were grade 4. CONCLUSION Melflufen plus dexamethasone showed clinically meaningful efficacy and a manageable safety profile in patients with heavily pretreated RRMM, including those with triple-class–refractory and extramedullary disease.

scholarly journals EPID-07. HEMATOLOGICAL ADVERSE EVENTS IN GLIOBLASTOMA PATIENTS TREATED WITH TEMOZOLOMIDE

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi75-vi76
Author(s):  
Catherine Garcia ◽  
Zin Myint ◽  
Rani Jayswal ◽  
Allison Butts ◽  
Heidi Weiss ◽  
...  
Keyword(s):  
Overall Survival ◽  
Adverse Events ◽  
Protective Factor ◽  
Significant Proportion ◽  
Progression Free Survival ◽  
Free Survival ◽  
Significant Difference ◽  
History Of ◽  
Grade 3 ◽  
Severe Grade

Abstract BACKGROUND Temozolomide (TMZ) is the cornerstone for glioblastoma (GBM) treatment. A significant proportion of patients develops hematologic toxicities with limited investigations on outcomes and risk factors for their development. METHODS Our study combines data from the two largest group trials, RTOG 0525 and RTOG 0825, to analyze serious hematologic adverse events (HAE) associated with TMZ therapy for GBM. We analyzed frequency and outcomes of HAE during chemoradiation. RESULTS 1154 patients were evaluated with a median age of 57 years. Over 79% of patients developed HAE during the entire course of GBM treatment. During chemoradiation the most common HAE during chemoradiation was lymphopenia (41.5%), followed by thrombocytopenia (39.0%), and anemia (35.3%). Of these, 34.1% were severe (Grade 3 or 4) and 65.9% were mild (grade 1 or 2). During maintenance the most common HAE was leukopenia (50.7%), followed by neutropenia (50.4%), and lymphopenia (45.3%). MGMT methylation was not associated with HAEs. A history of HAEs during chemoradiation was a protective factor for developing HAEs during maintenance. MGMT methylated and age younger than 50 were protective factors for mortality. Patients that presented HAEs anytime during treatment had a longer overall survival and progression free survival. There was no significant difference in survival between mild or severe HAEs. CONCLUSION HAE are common during chemoradiation with TMZ for GBM, but are more commonly grade 1 or 2 per CTCAE. HAE during GBM treatment is associated with decreased progression free survival and overall survival.

scholarly journals Real-World Data for Lenvatinib in Radioiodine-Refractory Differentiated Thyroid Cancer (RELEVANT): A Retrospective Multicentric Analysis of Clinical Practice in Austria

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
G. Rendl ◽  
B. Sipos ◽  
A. Becherer ◽  
S. Sorko ◽  
C. Trummer ◽  
...  
Keyword(s):  
Overall Survival ◽  
Thyroid Cancer ◽  
Progression Free Survival ◽  
Duration Of Treatment ◽  
Real World Data ◽  
Free Survival ◽  
Proven Efficacy ◽  
Grade 3 ◽  
Dose Reductions ◽  
Retrospective Multicenter Study

Background. Lenvatinib has proven efficacy in progressive, radioiodine- (RAI-) refractory thyroid cancer (TC). Dose reductions are commonly performed due to decreased tolerability and adverse effects. This retrospective multicenter study analyzed overall survival (OS) and progression-free survival (PFS) and tolerability in the Austrian patient population treated with lenvatinib. Methods. Clinical data of 43 patients (25 males and 18 females) with a median age of 70 years (range: 39–91 years) and RAI-refractory TC with metastases to the lymph nodes (74%), lungs (86%), bone (35%), liver (16%), and brain (12%) were analyzed. The mean duration of treatment with lenvatinib was 26.6 ± 15.4 months with dosage reductions required in 39 patients (91%). Results. PFS after 24 months was 71% (95% CI: 56–87), and overall survival (OS) was 74% (95% CI: 60–88), respectively. OS was significantly shorter ( p = 0.048 ) in patients with a daily maintenance dosage ≤ 10 mg (63%) (95% CI: 39–86) as compared to patients on ≥ 14 mg lenvatinib (82%) (95% CI: 66–98) daily. Dose reduction was noted in 39 patients (91%). Grade ≥3 toxicities (hypertension, diarrhea, weight loss, and palmar-plantar erythrodysesthesia syndrome) were most common leading to discontinuation of lenvatinib in 7 patients (16%). Conclusion. Lenvatinib showed sustained clinical efficacy in patients with metastatic RAI-refractory TC even with reduced maintenance dosages over years. The effects were comparable to the registration trial, although patients had a higher median age and, more commonly, dose reductions.

scholarly journals Subcutaneous Administration of Bortezomib in Combination with Thalidomide and Dexamethasone for Treatment of Newly Diagnosed Multiple Myeloma Patients

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Shenghao Wu ◽  
Cuiping Zheng ◽  
Songyan Chen ◽  
Xiaoping Cai ◽  
Yuejian Shi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Adverse Events ◽  
Subcutaneous Administration ◽  
Progression Free Survival ◽  
The Other ◽  
Newly Diagnosed ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Grade 3

Objective. To investigate the efficacy and safety of the treatment of the newly diagnosed multiple myeloma (MM) patients with the therapy of subcutaneous (subQ) administration of bortezomib and dexamethasone plus thalidomide (VTD) regimen.Methods. A total of 60 newly diagnosed MM patients were analyzed. 30 patients received improved VTD regimen (improved VTD group) with the subQ injection of bortezomib and the other 30 patients received conventional VTD regimen (VTD group).The efficacy and safety of two groups were analyzed retrospectively.Results. The overall remission (OR) after eight cycles of treatment was 73.3% in the VTD group and 76.7% in the improved VTD group (P>0.05). No significant differences in time to 1-year estimate of overall survival (72% versus 75%,P=0.848) and progression-free survival (median 22 months versus 25 months;P=0.725) between two groups. The main toxicities related to therapy were leukopenia, neutropenia, thrombocytopenia, asthenia, fatigue, and renal and urinary disorders. Grade 3 and higher adverse events were significantly less common in the improved VTD group (50%) than VTD group (80%,P=0.015).Conclusions. The improved VTD regimen by changing bortezomib from intravenous administration to subcutaneous injection has noninferior efficacy to standard VTD regimen, with an improved safety profile and reduced adverse events.

Cyclophosphamide, Adriamycin, Vincristine and Prednisone Plus Rituximab (CHOP-R) in Fludarabine (F) Refractory Chronic Lymphocytic Leukemia (CLL) or CLL with Autoimmune Cytopenia (AIC) or Richter's Transformation (RT): Final Analysis of a Phase II Study of the German CLL Study Group

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2860-2860
Author(s):  
Petra Jenke ◽  
Barbara Eichhorst ◽  
Raymonde Busch ◽  
Nadine Anheier ◽  
Ulrich Duehrsen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Phase Ii ◽  
Research Funding ◽  
Progression Free Survival ◽  
Response Rates ◽  
Median Number ◽  
Response Evaluation ◽  
Free Survival ◽  
Richter's Transformation ◽  
Grade 3

Abstract Abstract 2860 Introduction: In the last decade, important progress has been achieved in the treatment of CLL through the use of purine analog-based chemoimmunotherapies. Several conditions remain a challenge, often with a poor outcome. Amongst these therapeutic problems are Richter's transformation (RT), refractoriness to F-based therapies (Fref), and the occurrence of AIC, which are sometimes induced by F. Fref and RT pts have a very poor prognosis with an estimated overall survival (OS) of only 10 and 8 months (mos), respectively. Therefore, therapeutic alternatives are urgently warranted. CHOP-R has improved the outcome of pts with aggressive non-Hodgkin's lymphoma. To test the efficacy and tolerability of the CHOP-R regimen in CLL patients with RT, Fref, or AIC, the GCLLSG initiated a prospective phase II trial. Material and Methods: 62 patients were included in the study. Due to protocol violations, 2 patients were excluded. Within the group of Fref pts, the medical review detected 11 patients who had received pre-treatment with F (Fpret), but were not refractory according to the updated guidelines (Hallek et al., Blood 2008). Thus, 26 pts were classified as Fref/pret, 19 pts as AIC and 15 pts as RT. All patients received CHOP every 3 weeks (cyclophosphamide 750mg/m2, adriamycin 50mg/m2 and vincristine 1, 4mg/m2 d1; prednisone 100mg/m2 d1–5). Rituximab was added starting with the 2nd cycle (375mg/m2 on each d0, and 21 days after the last CHOP-R). RT pts received up to 8, Fref/pret and AIC up to 6 courses of CHOP-R. In case of PD after 3 cycles, pts went off-study. The primary endpoints were remission rate, quality and duration of response. Results: 79%, 73%, and 40% of AIC, Fref/pret, and RT pts were male, respectively. The median age was 65 years (y) for Fref/pret-pts, 66y in the AIC and 69y in the RT group. Binet stages for Fref/pret pts were: A: 8%; B: 27% C: 65 %. All but 3 AIC pts were at Binet stage C. Initial RT stages according to Ann Arbor were: II: 13%, III: 13%, IV 73%. The median number of previous therapies were 3 for Fref/pret, 2 for AIC and 2 for RT. A total of 314 cycles were administered, with a median number of 3 cycles for AIC and Fref pts and a median number of 4 cycles for the RT group. Due to toxicity 73% of cycles in the Fref/pret group, 66% in the AIC and 87% in the RT group were dose-reduced. 69% of Fref/pret-pts and 58% of AIC-pts received full 6 cycles of therapy and only 40% of RT-pts completed 8 cycles of therapy. Treatment was stopped in 6 pts because of PD. Due to treatment related toxicity treatment was stopped in 16 pts (27%). Treatment related mortality was 3% (2 pts). Treatment toxicity was reported according to NCI common toxicity criteria (CTC) version 2.0. Adverse events grade 3 or 4 for anemia, neutropenia and thrombocytopenia were documented in 75%, 55% and 65% of patients, respectively. Infections were the most common non-hematologic toxicity and occurred in 67%; severe infections CTC grade 3 or 4 occurred in 28%. All 26 Fref/pret-pts were available for response evaluation. CHOP-R achieved 54% PR, 35% SD and 12% PD. The median progression-free survival (PFS) and median treatment-free survival (TFS) were 11 and 14 mos. OS was 27 mos with a significant difference concerning F-ref (n=15) and F-pret (n=11) pts (17 vs. 35m; p=0.05). We evaluated the response of all 15 RT-pts with 60% PR, 7% CR, 13% SD and 20% PD. The PFS was 15 mos, TFS was 17 mos and OS 27 mos. 17 AIC pts were available for response evaluation with 82% PR, 6% SD and 12% PD. The PFS and TFS were only 14 and 16 mos. The OS was 50 mos. The population had a high incidence of unfavourable genetic markers: deletion of chromosome 17p [del(17p)] was detected in 24%, del(11q) in 34% and unmutated IGHV in 70%. 85% had high levels of serum thymidine kinase (sTK > 10 U/l), and 49% had high levels of ß2-microglobulin (ß2M > 3.5 mg/l). Patients with del(17p) had an unfavourable response rate and achieved significant less a PR or CR (36% vs. 76%; p=0.03). Multivariate analyses showed that del(17p) and ECOG performance status had a negative prognostic impact on OS (p<0.0001). Moreover the presence of a del(17p) predicted a short PFS (6 vs. 16.9 mos; p=0.001). Conclusion: CHOP-R achieves promising response rates in CLL patients with Fref and RT and very good response rates in patients with AIC. However, the progression-free survival and overall survival remain unsatisfactory. Therefore, CHOP-R might be used as induction therapy prior to allogeneic stem cell transplantation in physically fit patients. Disclosures: Eichhorst: Hoffmann La Roche: Honoraria, Research Funding, Travel Grants; Mundipharma: Research Funding, Travel Grants; Gilead: Consultancy. Dreyling:Roche: Research Funding, Scientific advisory board, Speakers Bureau. Bergmann:Celgene: Honoraria. Stilgenbauer:Hoffmann La Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Travel Grants. Fink:Hoffmann La Roche: travel grants. Fischer:Hoffmann La Roche:. Wendtner:Hofmann-La Roche: Consultancy, Honoraria, Research Funding. Hallek:Roche: Consultancy, Honoraria, Research Funding; Mundipharma: Research Funding; Celgene: Honoraria.

Efficacy and Safety Of Treatments For Relapsed Or Refractory Mantle Cell Lymphoma (MCL): Results Of a Systematic Literature Review

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5099-5099
Author(s):  
Annete Njue ◽  
Peter C Trask ◽  
Ann Colosia ◽  
Robert Olivares ◽  
Shahnaz Khan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Literature Review ◽  
Systematic Literature Review ◽  
Comparative Studies ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Patient Characteristics ◽  
Refractory Disease ◽  
Efficacy And Safety ◽  
Free Survival

Abstract Background MCL accounts for approximately 3%-10% of non-Hodgkin’s lymphoma (NHL) cases. The aggressive course of MCL includes rapid disease progression, with temporary responses to chemotherapy, and a high recurrence rate. However, the clinical course is variable with overall survival ranging from 6 months to more than 10 years. Although the median survival with MCL is 3-4 years, for those with relapsed or refractory disease, survival is much shorter. This systematic literature review (SLR) was designed to exhaustively collect and review information on the clinical efficacy and safety of the different interventions used in the treatment of refractory/relapsed MCL, and if possible to perform a meta-analysis. Methods Electronic databases (PubMed, Cochrane Library, Embase) were systematically searched for studies assessing the efficacy of safety of treatments for relapsed or refractory MCL published from 1997 to August 2, 2012. In addition, conference abstracts, bibliographic reference lists of included articles and recent reviews, and the Clinicaltrials.gov database were searched for phase 2, 3, or 4 studies displaying results, potentially unpublished in peer-reviewed journals. Main efficacy outcomes included objective response rate (ORR), complete response, partial response, duration of response, progression-free survival (PFS), and overall survival (OS). Safety endpoints focused on grade 3/4 toxicities and treatment withdrawals due to toxicity. Studies had to report on relapsed or refractory MCL after at least one standard treatment and patients who were not eligible to receive high-dose chemotherapy or stem cell transplant (autologous or allogeneic). Mixed type NHL studies were required to report MCL outcomes separately for inclusion. Results A total of 3,308 publications were identified in the first pass of a broad SLR on NHL; of these, 67 provided relevant data for MCL representing 59 unique studies. Of the 59 studies, 6 were comparative (including 5 RCTs) and 53 were noncomparative single-arm studies; 35 evaluated single-agent regimens, and 24 evaluated combination therapies. A total of 40 different treatments were evaluated in the identified studies. Overall survival and PFS were infrequently reported. Criteria for relapsed or refractory were often not defined, with only 7 studies providing varied definitions. The ORR of active treatments in the few comparative studies ranged from 6%-83%, with most estimates between 45% and 60%. Progression-free survival was approximately 5-7 months with the exception of bortezomib + CHOP in which a 16-month PFS was noted; median OS for these studies ranged from 11-16 months, with 36 months for the aforementioned exception. In the single-arm studies, ORR ranged from 12%-100%, with most estimates from 30%-60%. Progression-free survival was approximately 5-12 months, except for bendamustine alone or in combination (∼21 months) and bortezomib in combination (∼18 months, but with large variability). Overall survival ranged from 12-24 months, with two notable exceptions: bortezomib combination (∼38 months) and temsirolimus in combination with rituximab (∼30 months). Some increase in PFS and OS was observed over the study period. The main safety concerns were related to thrombocytopenia (11-66%), neutropenia (15-100%), anemia (4-34%), and neuropathy (9-13%). Although patients’ MIPI category was collected, outcomes were not reported by this variable. Conclusions The results of this SLR confirm that survival is still low among treatments for relapsed or refractory MCL making this a continued area of unmet need. The small number of randomized trials makes it difficult to identify a standard of care. The lack of common treatments among the randomized controlled trials for MCL and the variability in the populations studied did not allow for a valid meta-analysis. Small sample size, infrequent reporting of OS/PFS, limited information on prior treatments/responses, and patient characteristics also make comparison of results difficult. Comparative studies demonstrating relative survival advantages of various therapies in relapsed or refractory MCL are needed, as is more information on the relation between MIPI scores and outcomes. In the absence of such evidence, management of relapsed or refractory disease should be based on individual patient characteristics and concerns regarding tolerability. Disclosures: Njue: RTI Health Solutions: Employment. Trask:Sanofi: Employment. Colosia:RTI Health Solutions: Employment. Olivares:Sanofi: Employment. Khan:RTI Health Solutions: Employment. Abbe:Sanofi: Employment. Police: RTI Health Solutions: Employment. Wang:RTI Health Solutions: Employment. Sherrill:RTI Health Solutions: Employment. Kaye:RTI Health Solutions: Employment. Awan:Lymphoma Research Foundation (Career Development Award): Research Funding.

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.

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