R-Vemp Is a Safe and Effective Chemo-Immunotherapeutic Regimen In Elderly Unfit DLBCL Patients: Report From a Single Center-Experience

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3042-3042
Author(s):  
Francesca Pavanello ◽  
Antonio Branca ◽  
Anna Colpo ◽  
Marco Pizzi ◽  
Rocco Cappellesso ◽  
...  
Keyword(s):  
Adverse Events ◽  
International Prognostic Index ◽  
Palliative Therapy ◽  
Single Center ◽  
First Line ◽  
Single Center Experience ◽  
First Line Therapy ◽  
Line Therapy ◽  
Highly Effective ◽  
Unfit Patients

Abstract Background and objectives The standard first-line therapy for patients with DLBCL includes R-CHOP or CHOP-like regimens; although these regimens are highly effective in the majority of DLBCL patients , elderly “unfit” patients do not tolerate these schedules and usually receive palliative therapy with a consequent dismal prognosis. Several polychemotherapy regimens combining low toxicity and a substantial anti-lymphoma activity have been tested in this clinical setting. In the pre-rituximab era, VEMP (etoposide, cyclophosphamide, mitoxantrone, prednisone) polychemotherapy was investigated initially in relapsed/refractory patients and subsequently as first line therapy and displayed fairly good outcomes. In this study, we present data from an Italian single-center experience evaluating the efficacy and tolerability of the association of Rituximab with VEMP (R-VEMP) in patients not eligible for standard R-CHOP therapy or its modifications (for example R-miniCHOP) because of age and/or comorbidities. Design and Methods From October 2006 to November 2012, 34 untreated patients aged 66 years and older (median age: 79) with DLBCL (26% GC, 48% non-GC, 26% ND) were treated with a combination chemotherapy including etoposide 150 mg/m2 day 1; cyclophosphamide 650 mg/m2 day 1; mitoxantrone 12 mg/m2 day 1; prednisone 60 mg/m2 day 1-5; rituximab 375 mg/m2 day 0). Sixty-eight percent of patients had high Charlson Comorbility Index; 62% had Ann Arbor stage III/IV disease; 47% had high or intermediate-high International Prognostic Index score. Results Twenty-six patients (76%) completed the scheduled treatment (4 or 6 cycles). The Overall Response Rate (ORR) was 71%: 19 patients (56%) obtained a Complete Response (CR), 5 (15%) achieved a Partial Response (PR); 3 patients (9%) were in stable disease and 7 (20%) had a progressive disease (among these latter, 6 patients were intermediate-high or high IPI score and had extranodal disease; all of these patients had high Charlson Comorbility Index). After a median follow-up of 20 months, 15 patients (44%) maintained a CR and only one patient relapsed within 14 months after achieving a CR. In this setting of patients the median Overall Survival (OS) was 20 months (range 1-78), the Event Free Survival (EFS) was 6 months (range 1-41). The treatment was well tolerated without therapy related mortality. Among the adverse events, the most common were: grade 3-4 temporary neutropenia (71%), grade 2 transitory anemia (29%) and febrile neutropenia (20%). G-CSF was administrated to 29 patients (85%) and erythropoiesis stimulating agents to 8 patients (24%). Conclusions These data suggest that R-VEMP is a well-tolerated and highly effective regimen in elderly “unfit” patients with DLBCL and could offer a valuable alternative choice for those patients not eligible for more toxic first line protocols. Considering the high rate of serious adverse events and the difficulty to completely administer the scheduled cycles, standard R-CHOP or CHOP-like therapy is applied with much less frequency to elderly unfit patients. R-VEMP could represent a reasonable regimen that warrants to be further explored, as an additional therapeutic option in order to overcome the low survival rate observed in this subgroup of patients. Disclosures: No relevant conflicts of interest to declare.

Comprehensive Geriatric Assessment (CGA) and ONCO-Mpi Predict Mortality in Diffuse Large B-Cell Lymphoma (DLBCL) in the Elderly: A Retrospective Evaluation in a Single Center Experience

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4206-4206
Author(s):  
Silvia Finotto ◽  
Dario Marino ◽  
Caterina Boso ◽  
Filippo Marino ◽  
Luca Canziani ◽  
...  
Keyword(s):  
High Risk ◽  
Activities Of Daily Living ◽  
Daily Living ◽  
Single Center ◽  
First Line ◽  
Curative Intent ◽  
Single Center Experience ◽  
First Line Therapy ◽  
Line Therapy ◽  
One Year

Abstract DLBCL is the most common type of non-Hodgkin lymphoma and it usually affects elderly patients, with a median age at diagnosis of 70 years and an incidence that rises with increasing age. Nevertheless patients > 70 years are rarely included in clinical trials and the management is often different according to local practice. A pre-treatment evaluation based on Performance Status (PS) or comorbidity index is not sufficient to identify patients suitable for treatment with curative intent. We retrospectively reviewed 93 patients with newly diagnosed DLBCL, ≥65 years old , treated from January 2009 to December 2015 at Veneto Institute of Oncology-IRCCS (median age 76 years, range 65-96). Twenty-eight patients (28) were older than 80 years. All but one received at least first line treatment. All patients were evaluated with CGA at diagnosis, based on Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL) and Cumulative Illness Rating Scale (CIRS). According to these variables they were classified into three categories named 'fit', 'vulnerable' and 'frail'. In addition, a cancer-specific modified multidimensional prognostic index (MPI), called Onco-MPI, was calculated for all patients. Onco-MPI score identify three risk score categories (low, moderate and high risk) that predict one-year mortality in older cancer patients. Onco-MPI was calculated according to a validate algorithm as a weighted linear combination of the following CGA domains: age, sex, ADL, IADL, PS, mini-mental state examination, body mass index, CIRS, number of drugs and the presence of caregiver. Cancer sites were also included in the model. Other features analyzed included clinical characteristics, treatment management and outcomes. In our cohort 48% of patients were at advanced Ann Arbor stage (III-IV) with intermediate-high or high risk IPI score in 31%. In 61% of patients we observed extranodal disease, mainly Waldeyer's ring and gastrointestinal tract. First line treatments received included R-CHOP (38%), R-COMP (R-CHOP with non-pegylated liposomial doxorubicin - 23%), R-CVP (14%), R-CEOP (3%), high dose methotrexate (4 patients with primary central nervous system lymphoma), R-VACOP-B (3%), R-Bendamustine in 2 patients and radiotherapy alone was used in 5 patients. Sixty-eight patients (84%) completed the planned cycles of immunochemotherapy. In this group 48,5% required dose reduction for subsequent cycles of treatment because of side effects, in particular hematological toxicities of grade 3-4 or neurological toxicities. In 23 chemotherapy-treated patients initial doses were reduced according to CGA . We observed, after first line therapy, complete response in 63% and partial response in 21%, 8% of patients experienced a disease progression at the end of treatment and 8% died during first line therapy because of lymphoma progression. At time of diagnosis 49% of patients were considered fit at CGA, 16% vulnerable and 35% frail. According to onco-MPI 24 patients (26%) were at low risk of one year mortality, 31 (33%) at medium risk and 38 (41%) at high risk. With a median follow up of 41,1 months the overall survival (OS) of our cohort is 55,9% (95% CI 25,3-56,9). OS correlates with CGA ( 84,4% in fit patients, 31,2 % in vulnerable and 28,1% in unfit, p< 0,001) and Onco-MPI score seems to discriminate our cohort for one-year mortality (95% in low risk, 77% in moderate and 63% in high, p<0,01). OS also correlates with anthracycline administration (67,8% vs 33,3%, p<0,001) as well as the use of consolidation radiotherapy after chemotherapy induction ( 75% vs 49,3%, p <0,01). Our retrospective, single Center experience demonstrates that elderly DLBCL need a multidimensional evaluation at diagnosis in order to identify patients candidate to treatment with curative intent. CGA confirm its role for choosing correct management. Also Onco-MPI can be a useful tool even if more data are needed in lymphoma patients. Disclosures No relevant conflicts of interest to declare.

191 Association of immune related adverse events with the efficacy of immune checkpoint inhibitors in metastatic renal cell carcinoma

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A205-A206
Author(s):  
Vasilii Bushunow ◽  
Leonard Appleman ◽  
Roby Thomas
Keyword(s):  
Renal Cell Carcinoma ◽  
Adverse Events ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Checkpoint Inhibitors ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Kaplan Meier

BackgroundImmune checkpoint inhibitors (ICI) are first-line therapy for tumors including metastatic renal cell carcinoma (mRCC). Use of ICI is complicated by diverse immune-related adverse events (irAEs), which can add significant morbidity but are also associated with improved efficacy of therapy.1 2 Risk factors for development of irAE are still poorly understood. We hypothesized that patients with mRCC treated with ICI as first-line therapy have higher rates of developing irAE’s than patients previously treated with other therapies.MethodsWe conducted a single-institution, retrospective medical record review of patients with mRCC treated with immune-checkpoint inhibitors from March 2011 through April 15, 2020. We identified therapy duration, and presence, severity, and treatment of adverse events. We defined overall survival as time elapsed from date of diagnosis until death or until completion of study. We classified severity of adverse events according to CTCAE guidelines. Statistical methods included univariate Cox proportional hazards and logistic regression models, and Kaplan-Meier curves were plotted for subgroups.ResultsA total of 64 unique charts were reviewed. 18 patients (28%) of patients were treated with ICI as first-line therapy. 28 patients (44%) experienced immune-related adverse events with a total of 40 irAE’s identified. Most irAE were grade I-II (78%), with 7 (17%) grade III and 1 (2.4%) grade IV irAE’s. Most common sites were skin (29%), thyroid (20%) and gastrointestinal (15%). Patients with irAE had increased survival compared to those who did not have irAE (median survival not reached, vs 139 weeks, p=0.0004) (figure 1). This finding remained after excluding patients who had only experienced dermatologic irAE (median survival not reached in non-derm irAE subgroup, vs 144 weeks for dermatologic or no irAE, p=0.01) (figure 2). Patients treated with ICI as first line therapy had greater rates of developing irAE (72%) than those who had prior therapies (32%) (OR 5.4; p = 0.006). There was no association between histology type and rate of irAE.Abstract 191 Figure 1Kaplan-Meier survival plot of OS between patients with any irAE and those without any irAEAbstract 191 Figure 2Kaplan-Meier survival plot of OS between patients with non-dermatologic irAE and those without any irAE or only dermatologic irAEConclusionsThe development of irAE’s in patients with mRCC treated with ICI is associated with longer survival. This study joins the growing body of evidence showing that presence of irAE’s is associated with increased treatment efficacy. Use of ICI as first-line therapy is associated with higher risk of irAE. Given growing use of ICI as first-line therapy, further study to predict onset and severity of irAE’s is required.AcknowledgementsHong Wang, PhD, for statistical support.Ethics ApprovalThis study was approved by the University of Pittsburgh Institutional Review Board. Approval number STUDY19100386.ReferencesElias R, Yan N, Singla N, Levonyack N, Formella J, Christie A, et al. Immune-related adverse events are associated with improved outcomes in ICI-treated renal cell carcinoma patients. J Clin Oncol 2019;37(7):S645.Verzoni E, Cartenì G, Cortesi E, et al. Real-world efficacy and safety of nivolumab in previously-treated metastatic renal cell carcinoma, and association between immune-related adverse events and survival: the Italian expanded access program. J Immunother Cancer 2019;7(1):99.

Sign in / Sign up

Export Citation Format

Share Document