scholarly journals PVAG Regimen (Prednisone, Vinblastine, Doxorubicin, Gemcitabine) Used in Real-Life Setting in First Line Therapy for Elderly Classical Hodgkin Lymphoma Patients: A Retrospective Study of Lysa Centers

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 11-11
Author(s):  
Guillaume Aussedat ◽  
Maryam Idlhaj ◽  
Amandine Durand ◽  
Xavier Roussel ◽  
Pauline Brice ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Overall Survival ◽  
Hodgkin Lymphoma ◽  
Real Life ◽  
Hematologic Toxicity ◽  
Classical Hodgkin Lymphoma ◽  
First Line ◽  
Real Life Setting ◽  
Grade 3 ◽  
Advisory Role

Introduction: Older patients with an age above 60 years with classical Hodgkin lymphoma (cHL) represent a proportion of 20% to 30% of all cHL. Older cHL patients are characterized by unfavorable prognostic factors with an aggressive disease, a poor tolerance to chemotherapy especially with bleomycin-induced lung toxicity resulting to a significant reduced survival as compared to younger patients. PVAG regimen (prednisone, vinblastine, doxorubicin, gemcitabine) was developed by the German Hodgkin Study Group (GHSG) to improve results and reduce toxicities of ABVD regimen. In a prospective phase II study of 55 early unfavorable and advanced-stage elderly HL patients (median age, 68 years), 78% achieved complete response (CR) with a 3-year progression free survival (PFS) and overall survival (OS) rates of 58% and 66%, respectively (Böll et al, Blood 2011) with favorable toxicity profile. To the best of our knowledge, there is no report that described efficacy and toxicity of this protocol in real-life setting. Methods: Between June 2011 and February 2020, 49 elderly patients with cHL received first-line chemotherapy with PVAG (Prednisone 40 mg/m2, Vinblastine 6 mg/m2, Doxorubicin 50 mg/m2, Gemcitabine 1000 mg/m2, or adapted-dose of PVAG) in 6 LYSA centers. All medical records were reviewed for clinical and biological characteristics, modality of treatment, responses and outcome. Comorbidities were evaluated according to the cumulative illness rating scale for geriatrics (CIRS-G) and treatment-related toxicity according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE). Results: The median age of the 49 patients was 76 years (range, 61-87) with 44 patients ≥70 years old (69%) and 27 male (55%). Ann Arbor stages were as follows: II (n=16, 33%), III (n=12, 24%), IV (n=21, 43%). Altered performance status (PS 2-4) was presented in 35% of patients and B symptoms in 59%. IPS was ≥3 in 32 (65%) patients. CIRS-G Grade 3 or 4 in two or more categories was observed in 11 patients (22%) and 22 patients (43%) had a cumulative CIRS-G score over 6. Patients received a median of 6 cycles (range 1-8), 21 of them (43%) received adapted dose of PVAG. Seven patients (14%) received radiotherapy after respectively 3, 4, 6, or 8 cycles of PVAG. At the end of PVAG regimen, 26 patients were in CR (53%), 4 PR (8%), 19 patients progressed (39%). For the 46 patients who were evaluated by PET-CT after chemotherapy, the CR and PR rates were 52% and 13% with 35% of patients with stable or progressive diseases. For hematologic toxicity, 6 patients (12%) developed febrile neutropenia, 22 (45 %) had grade III-IV neutropenia; 8 (16 %) a grade 3-4 thrombopenia; 17 (35%) grade 3-4 anemia. Extra-hematologic toxicities were mild with three patients (6%) with grade 3-4 mucositis, 2 (4%) grade 3-4 nausea, 5 (10%) with grade 3-4 neuropathy, 3 (6%) acute heart toxicity. With a median follow up of 33,2 months (range, 14,3 -53,7), 26 (53%) patients progressed or relapsed. The median PFS was 21,6 months with a 3-year PFS rate of 48,6% (95%CI, 36,3-65,1). The median overall survival (OS) was 66,5 months with a 3-year OS rate of 73,7% (95%CI, 61,2-88,8). The cause of death was HL in 8 patients (16%), infection in 2 (4%); one toxic death occurred (sepsis after first cycle of PVAG). In univariate analysis, PFS (HR: 2,36, 95CI, 1,01-5,48, P=0.0,046) and OS (HR: 4,23, 95%CI, 1,15-15,6, P=0.03) were adversely affected by high number of medications (>3). OS was adversely affected by grade 3-4 CIRS-G in ≥2 categories (HR: 3,63, 95%CI, 1,23-10,71, P=0.019). Age, IPS, presence of B symptoms, lymphopenia, anemia, low albumin level, CIRS-G>6 did not affect outcome. Conclusions:Our real-life evaluation of PVAG regimen showed that patients were older than those included in the pivotal clinical trial and 58% of patients received adapted-dose of chemotherapy. We confirmed the favorable safety profile of this protocol. Using TEP-scan evaluation, the CR rate was 52%. Survival analyses supported initial results obtained in clinical trial. Combinations with immunotherapies with clinical activity in cHL should be evaluated to improve results of this regimen. Disclosures Brice: Takeda: Consultancy; Roche: Consultancy. Salles:Epizyme: Honoraria, Other: consultancy or advisory role; Kite, a Gilead Company: Honoraria, Other: consultancy or advisory role ; Janssen: Honoraria, Other: consultancy or advisory role; BMS/Celgene: Honoraria, Other: consultancy or advisory role; Takeda: Honoraria; Karyopharm: Honoraria; Genmab: Honoraria, Other; Debiopharm: Consultancy, Honoraria, Other: consultancy or advisory role; MorphoSys: Honoraria, Other: consultancy or advisory role; Novartis: Honoraria, Other: consultancy or advisory role; Roche: Honoraria, Other: consultancy or advisory role; Abbvie: Other: consultancy or advisory role; Autolos: Other: consultancy or advisory role. Deau Fischer:Takeda: Consultancy; Roche: Consultancy.

Randomized strategical trial of chemotherapy in metastatic colorectal cancer (FFCD 2000–05): Preliminary results

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4069-4069 ◽  
Author(s):  
O. Bouché ◽  
M. Castaing ◽  
P. L. Etienne ◽  
P. Texereau ◽  
D. Auby ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Progression Free Survival ◽  
Hematological Toxicity ◽  
Hematologic Toxicity ◽  
First Line ◽  
Number Range ◽  
Preliminary Results ◽  
Grade 3

4069 Background: The survival benefit of using a combination therapy instead of keeping it for a second line (L2) has not been demonstrated in metastatic colorectal cancer. The purpose of this trial was to compare the efficacy of simplified LV5FU2 (s) followed by FOLFOX6 (arm A) to FOLFOX6 followed by FOLFIRI (arm B) on progression-free survival after two lines of chemotherapy. We present here preliminary results relating to toxicity, observance and overall survival. Methods: Inclusion criteria: a) non resectable metastases of histologically proven colorectal adenocarcinoma , b) evaluable disease (WHO criteria), c) absence of previous chemotherapy other than adjuvant. Treatment was as follows: LV5FU2s = at day 1, folinic acid 400 mg/m2, 5-FU bolus 400 mg/m2 and continuous infusion over 46 hours 2,400 mg/m2/2 weeks; FOLFOX6 = LV5FU2s + oxaliplatin 100 mg/m2 at day 1; FOLFIRI = LV5FU2s + irinotecan 180 mg/m2 at day 1. Results: 410 pts out of 570 initially planned (early stopping due to slow accrual and new treatments) were included from 02/2002 to 02/2006 (205 in each arm). Median follow-up was 25 months. The median number (range) of cycles (28 days) in first line (L1) was respectively 5 (1–24) and 6 (1–24) in the arms A and B (p=0.01), and for L2 (152 and 144 pts in the arms A/B): 5 (1–17) and 3 (1–33) (NS). In the arms A and B, 74% and 70% of pts had L2. L1 was stopped for toxicity for 1% and 16% of the pts in arms A and B (p<0.0001); L2 respectively for 15% and 2% pts (p<0.0001). The percentages of pts presenting at least a grade 3–4 hematologic toxicity (mainly neutropenia) by arm were: 6% versus 37% (p<0.0001) for L1 and 30% versus 27% (NS) for L2; grade 3–4 non hematological toxicity (grade 2–4 neurotoxicity): 26% (1%) versus 56% (64%)(p<0.0001; p<0.0001) for L1 and 54% (60%) versus 46% (40%) of the pts for L2 (NS; p<0.01). No toxic death was observed in the arm A against 5 in the arm B: 3 in L1 and 2 in L2. Overall survival medians were 17 and 16 months in arms A/B (logrank p=0.64) (preliminary results, 291 observed deaths). Conclusions: This trial does not show any substantial difference in treatment duration and overall survival between both arms and shows a more important toxicity in the arm with first line combined chemotherapy. No significant financial relationships to disclose.

scholarly journals Bendamustine Improves Clinical Outcome in Chronic Lymphocytic Leukemia (CLL) According to Different Clinical and Biological Prognostic Factors

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5668-5668
Author(s):  
Giovanni Del Poeta ◽  
Maria Ilaria Del Principe ◽  
Dario Ragusa ◽  
Pietro Bulian ◽  
Francesco Buccisano ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Elderly Patients ◽  
Conflicts Of Interest ◽  
Statistical Significance ◽  
Univariate Analysis ◽  
Real Life ◽  
Median Number ◽  
Hematologic Toxicity ◽  
First Line ◽  
Grade 3

Abstract Bendamustine has been demonstrated to be effective for the treatment of CLL, either alone compared with chlorambucil (Knauf et al, JCO 2009 and BJH 2012) or in combination with monoclonal antibodies such as rituximab both in second or more lines (Fischer et al, JCO 2011) and in first line treatment (Fischer et al, JCO 2012). However, the relationship between its activity with clinical and biological prognosticators has been addressed only in few studies. For this purpose, we evaluated the efficacy and safety of bendamustine, in a real-life contest, on 56 patients, median age 66 years (41-80), median number of previous regimens 1 (0-3, 32% previously untreated). Bendamustine was given for a median number of 6 cycles (70-90 mg/m2), in 82% of cases with rituximab at conventional doses. Overall (ORR) and complete response (CRR) rates were 73% and 44.6%, respectively. Obviously, CRR was higher (83.3%) for 18 patients treated in first line. A significant correlation was found between lower ORR and lymphocyte doubling time <12 months (OR 4.30; P=0.019), thus suggesting that a high proliferation rate may confer a reduced response to bendamustine. As already previously reported, there was a relationship between ORR and number of prior treatments in univariate analysis (OR 0.23; P=0.0055). Interestingly, there was also a significant correlation between lower ORR and the higher expression (>30%) of alpha-4 integrin CD49d (OR 13.0; P=0.018), an important marker of bad prognosis in CLL (Bulian et al, JCO 2014). On the other hand, no significant correlations were found between ORR and CD38, ZAP-70 or IGHV mutational status. Similarly, no significant correlations were noted between ORR and FISH cytogenetics, excluding del(17)p, or NOTCH1 mutations, thus confirming the independence of response to bendamustine from some well-known important biologic prognostic factors. In fact, multivariate analysis confirmed a significant relationship only between ORR and TP53/del(17)p (OR 0.020; P=0.0015) and concomitant rituximab (OR 0.019; P=0.0074). The estimated 1-year OS and PFS were 57% and 86%, respectively. Side effects included grade 3-4 neutropenia, infections, thrombocytopenia and anemia which occurred in 21%, 12%, 12% and 5% of patients, respectively. Grade 3-4 non-hematologic toxicity, including infusion-related reactions, heart or kidney or liver failure were found almost exclusively in elderly patients treated with bendamustine after two or more lines of therapy (12.5%). In multivariate analisys of OS, calculated from the end of treatment with bendamustine, only response to bendamustine (P=0.008) was confirmed to be an independent prognostic factor, while both the number of previous therapies and the concomitant use of rituximab demonstrated no statistical significance. These our results confirm both the activity and safety of bendamustine, particularly in combination with rituximab, also in the setting of elderly patients, often affected by two or three comorbidities. Noteworthy, this effectiveness appears to be present also in patients with unfavorable clinical and biological features, excluding del(17)p or TP53 mutations, in which the employment either of modern oral BCR inhibitors or of BH3 mimetics anti-Bcl-2 will be definitely active, also in combination with the same bendamustine. Disclosures No relevant conflicts of interest to declare.

scholarly journals BEGEV SALVAGE REGIMEN IN RELAPSED/REFRACTORY CLASSICAL HODGKIN LYMPHOMA: A REAL‐LIFE EXPERIENCE

2021 ◽  
Vol 39 (S2) ◽  
Author(s):  
A. Morigi ◽  
V. Stefoni ◽  
L. Argnani ◽  
M. Carella ◽  
B. Casadei ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Life Experience ◽  
Real Life ◽  
Classical Hodgkin Lymphoma ◽  
Salvage Regimen

scholarly journals Abiraterone in chemotherapy-naive patients with metastatic castration-resistant prostate cancer: a systematic review of ‘real-life’ studies

2018 ◽  
Vol 10 (10) ◽  
pp. 305-315 ◽  
Author(s):  
Michele Marchioni ◽  
Petros Sountoulides ◽  
Maida Bada ◽  
Sebastiano Rapisarda ◽  
Cosimo De Nunzio ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Adverse Events ◽  
Meta Analysis ◽  
Real Life ◽  
Castration Resistant Prostate Cancer ◽  
The Real ◽  
Castration Resistant ◽  
Real Life Setting ◽  
Grade 3 ◽  
Baseline Psa

Background: To assess the efficacy and safety of treatment with abiraterone acetate (AA) in chemotherapy-naïve men with metastatic castration-resistant prostate cancer (mCRPC) in the ‘real-life’ setting. Methods: Data acquisition on the outcomes of the use of AA in chemotherapy-naive patients with mCRPC was performed by a MEDLINE comprehensive systematic literature search using combinations of the following key words: ‘prostate cancer’, ‘metastatic’, ‘castration resistant’, ‘abiraterone’, ‘real life’, and excluding controlled clinical trials (phase II and III studies). Identification and selection of the studies was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) criteria. Outcomes of interest were overall survival (OS), progression-free survival (PFS), 12-week 50% reduction in prostate-specific antigen (PSA), and grade 3 and higher adverse events. Data were narratively synthesized in light of methodological and clinical heterogeneity. Results: Within the eight identified studies that fulfilled the criteria, a total of 801 patients were included in the meta-analysis. Baseline PSA ranged between 9.5 and 212.0 ng/ml. Most of the patients had bone metastases. Duration of treatment with AA was longer in the studies with lower baseline PSA levels. The median OS ranged between 14 and 36.4 months. The PFS, assessed according to different definitions, ranged from 3.9 to 18.5 months. A 50% PSA reduction at 12 weeks was reached by a variable percentage of patients ranging from 36.0% to 62.1%. Finally, the rate of grade 3 and higher adverse events was reported in three studies and ranged from 4.4% to 15.5%. Conclusions: Despite the high grade of heterogeneity among studies, treatment with AA seems to ensure good survival outcomes in the ‘real-life’ setting. However, prospective studies based on patients’ characteristics being more similar to ‘real-life’ patients are necessary.

scholarly journals The Outcomes of Nivolumab Fixed Dose 40 Mg Therapy in Patients with Relapsed or Refractory Classical Hodgkin Lymphoma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 6-6
Author(s):  
Liudmila Fedorova ◽  
Kirill Lepik ◽  
Polina Kotselyabina ◽  
Elena Kondakova ◽  
Yuri Zalyalov ◽  
...  
Keyword(s):  
Adverse Events ◽  
Disease Progression ◽  
Hodgkin Lymphoma ◽  
Median Number ◽  
Fixed Dose ◽  
Published Data ◽  
High Dose ◽  
Efficacy And Safety ◽  
Classical Hodgkin Lymphoma ◽  
Grade 3

Background Currently, the recommended dose of nivolumab for patients with relapsed or refractory classical Hodgkin lymphoma (r/r сHL) is 3 mg/kg. Nevertheless, published clinical cases indicate the possible efficacy of lower doses of nivolumab. Moreover, experimental studies provided the rationale for possible reduction of nivolumab dose in patients with solid tumors (Agrawal et al. 2016). The presented data creates prerequisites for studying the lower nivolumab doses efficacy and safety in the r/r cHL therapy. Patients and Methods This study included 42 patients (14 male/28 female) with r/r cHL who were treated with nivolumab 40 mg every 2 weeks. The median age of patients was 36 (22-53) years. The median number of prior therapy lines was 4 (2-7). Prior treatment contained high dose chemotherapy with ASCT in 9 pts (21%), brentuximab vedotin in 14 pts (33%) and allo-HSCT in 1 pt (2%). Four pts (9,5%) had the partial response (PR) and the remaining 38 pts (90,5%) had the disease progression (PD) at the moment of nivolumab initiation. B-symptoms were present in 23 pts (55%), ECOG status was grade 0-I in 25 pts (59,5%), grade II in 12 pts (29%), grade III in 4 pts (9,5%) and grade IV in 1 pt (2%). The primary endpoint was the overall response rate (ORR) determined by positron-emission tomography/computed tomography (PET/CT) using LYRIC criteria every 3 months. Key secondary endpoints included progression-free survival (PFS) and overall survival (OS). Adverse events (AE) were evaluated according to CTCAE 4.03. The patient group characteristics were evaluated using descriptive statistics methods, the survival analysis was performed using Kaplan-Meyer method (SPSS Statistics v.17). Results The median number of nivolumab cycles was 24 (2-38). The response was evaluated in 41 out of 42 pts. The ORR was 66%. The best response included complete response (CR) in 39%, PR in 27%, stable disease in 5%, PD in 2%, indeterminate response (IR) in 27% of pts. With a median follow-up of 27,5 mo (11,3-34,5) 41 pts (97,6%) were alive, the median OS was not reached. The 2-year PFS was 44,5% (95% CI, 28,2-59,6) The nivolumab therapy was discontinued in 39 pts (93%) due to scheduled discontinuation in 14 pts (33%), PD in 13 pts (31%), grade 3-4 AE in 2 pts (5%), change of therapy because of insufficient response in 6 pts (14%) and other reasons in 4 pts (10%). The progression of disease during nivolumab therapy was present in 14 (33%) pts and after nivolumab discontinuation in 6 (14%) pts. After disease progression 30 pts (71%) were retreated with nivolumab monotherapy or in combination with chemotherapy. The median time to additional therapy was 14,5 mo (4,2 -32,9). The adverse events of any severity were observed in 30 pts (71%). Grade 3 or higher AE were present in 4 pts (9,5%), including grade 3 arthralgia, grade 3 anemia, grade 4 pneumonia and pneumonitis, grade 4 increased level of alanine aminotransferase and grade 5 MDS in 1 pt. A significant reduction of PD1+CD3+ cell population of peripheral blood lymphocytes was observed after first nivolumab cycle (median 0.7% (0-1.7) versus 33% (15.7-80.1) before therapy initiation, p = 0.02, Wilcoxon signed-rank test). Conclusion Our study demonstrated the efficacy and safety of nivolumab 40 mg therapy. The presented results are comparable to previously published data of nivolumab 3 mg/kg therapy in patients with r/r cHL. Thus, this creates a basis for further direct comparative study of nivolumab efficacy in different doses Disclosures No relevant conflicts of interest to declare.

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