scholarly journals First Line B+R in Elderly Patients with Indolent Non-Hodgkin's Lymphoma and Mantle Cell Lymphoma: A Real-World Experience

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4519-4519
Author(s):  
Rouslan Kotchetkov ◽  
David Susman ◽  
Lauren M. Gerard ◽  
Erica Dimaria ◽  
Derek Nay ◽  
...  

Abstract Background: Bendamustine plus rituximab (B+R) was established as a preferred first-line therapy for indolent non-Hodgkin's lymphoma (iNHL) and mantle cell lymphoma (MCL); however, few reports on the performance of this combination in the real-world setting in elderly patients are available to date. Methods: A retrospective review of adult patients over 70 years (elderly) vs younger (<70 years) with iNHL and MCL who received first-line B+R at our institution from June 2013 to January 2021. We assessed safety, acute and late toxicity, and efficacy of B+R in elderly patients, compared to younger group. Results: Among 201 assessed patients, 133 were elderly (mean age 77.9 years) and 88 younger (mean age 61.1 years) at time of B+R initiation. Baseline patient characteristics are presented in Table 1. There were more MCL in the elderly group: 20.3% vs 3.2% in the younger group. Significantly more patients in the elderly group had history of second malignancy. Prostate, breast, colon, and bladder cancer were more common in elderly, and lymphoid and thyroid in younger groups. Bulky lymphadenopathy, cytopenia, and constitutional symptoms were the most common indications for B+R initiation both in elderly (74.4%) and younger (79.26%) patients. Median number of B+R cycles was 6 for both groups. Mean dose of bendamustine received was 83.6 mg/m 2 in the elderly vs 88 mg/m 2 in the younger groups (p=0.0001). Full doses of bendamustine were given in 54% of elderly patients as compared to 79.5% younger patients. Treatment was delayed in 54% of the elderly and 43.2% of the younger patients. The mean delay time was similar in both groups: 20.1 [7-147] vs 17.1 [7-35 days]. The number of adverse events (AE) per patient was similar between the groups across each cycle (Table 2). Rituximab-associated infusion reactions were the most common adverse events in both groups. One patient in younger group developed prolonged neutropenia, lasting over 15 months. G-CSF support received 12.4% elderly and 22.7% younger patients. Nine patients (8%) in elderly and six patients (6.8%) in younger group (p=0.7604) developed transformed aggressive B-Cell lymphoma. Thirteen patients (11.5%) in elderly and five patients (5.7%) in younger group (p=0.1530) had secondary malignancies. Melanoma, metastatic squamous cell and renal carcinoma were more common in elderly group. Younger patients had metastatic squamous cell carcinoma and renal carcinoma, Kaposi sarcoma, MDS and thyroid cancer. Overall response rate was 91.2% in elderly group vs 98.9% in younger group, including complete remission in 71.7% vs 84.1%. Median follow-up was 42 months [4.0-97.0]. Although median overall survival (OS) was not reached in both groups, it was shorter in elderly compared to younger group (HR 0.24, CI 0.14-0.42, p<0.0001) (Figure 1A). Relapse rate was 10.6% in elderly vs 4.5% in younger groups. Median event free survival (defined as time between the first treatment and one of the following events: progressive disease, relapse or death) for follicular lymphoma, the most common histological subgroup in both cohorts, was shorter in the elderly compared to younger groups (82.0 months vs not yet reached; HR 0.19, CI 0.05-0.71, p=0.0385) (Figure 1B) Conclusion: In the real-world setting elderly patients had more advanced and high-risk disease, as well as higher ECOG status. B+R was associated with greater dose reduction and treatment delays. Adverse events profile and incidence did not differ significantly from the younger group. Response rates were lower, but relapse rate was higher in elderly patients. OS was inferior in elderly patients as compared to the younger group, due to higher rate of relapse and secondary malignancies. Figure 1 Figure 1. Disclosures Prica: Astra-Zeneca: Honoraria; Kite Gilead: Honoraria.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19540-e19540
Author(s):  
Rouslan Kotchetkov ◽  
David Susman ◽  
Lauren Gerard ◽  
Erica DiMaria ◽  
Derek Wayne Nay

e19540 Background: Bendamustine plus rituximab (B+R) was established as a preferred first line therapy for patients with previously untreated indolent non-Hodgkin’s lymphoma based on the BRIGHT and STIL trials. However, only few reports on efficacy and safety data of this combination in the real-world setting are available to-date. Methods: We conducted a retrospective review of patients who received therapy with standard doses of B+R in our cancer center from June 2013 to January 2021. Patients with indolent non-Hodgkin’s lymphoma (iNHL) and mantle cell lymphoma (MCL) who received more than one cycle of B+R were evaluated. Results: Amongst a total of 201 patients 56% were males and 44% females. Median age at B+R initiation was 72 years (range 34-94). Follicular lymphoma (FL) (50.3%), marginal zone lymphoma (MZL) (19.4%), and lymphoplasmacytic lymphoma (LPL) (14.5%) were the most common iNHL. Stage 3 and 4 diseases represented 19.9% and 68.6% of patients. Extranodal disease was found in 35.8%. The proportion of patients with high risk disease was 48.5% for FL (FLIPI ≥3), 86.6% for LPL (WMISS score ≥2), and 80.5% for MCL (MIPI score ≥6.2). Prior history of secondary malignancy had 23.4% of patients; 11.4% patients had ECOG 3. Most common indications for B+R initiation were bulky symptomatic lymphadenopathy (69.1%), cytopenia (36.8%) and constitutional symptoms (36.8%). Fifty-eight percent of patients had more than one indication for therapy. Median number of B+R cycles delivered was 6 (range: 1-6), median dose of bendamustine was 90 mg/m2 (range 45-90). Full doses of treatment were given in 66.7% of patients, reduced in 33.3% with mean dose 78.3 mg/m2. A total of 50.8% completed 6 cycles with no delays, in 49.2% treatment was delayed (mean delay time 1.8 weeks). Overall response was 94.5%, with 77.6% complete and 16.9% partial remission. Median duration of follow-up was 35 months (range: 4-91). At the end of follow-up, event free survival (EFS) was 77.1% and overall survival (OS) was 79.6%. Six percent of patients relapsed, 8% developed secondary hematological malignancies, including 14 cases of aggressive B-cell lymphoma and 2 cases of MDS. 16.9% of patients required support with G-CSF. Grade 3-4 neutropenia was recorded in 22.4%, febrile neutropenia in 7.5%, grade 3-4 anemia in 7.9%, and grade 3-4 thrombocytopenia in 3.9% of patients. Rituximab-associated infusion reactions, skin rash, thrombophlebitis, and infection were the most common non-hematological adverse events. A total of 80.6% of patients proceeded to rituximab maintenance. Conclusions: B+R chemoimmunotherapy is feasible to administer in non-clinical trial setting. Despite more dose reduction as compared to STIL trial, B+R retained its efficacy with comparable EFS and OS. No new adverse events or increase in secondary malignancies were found.


2020 ◽  
Vol 42 (2) ◽  
pp. 194
Author(s):  
Sergio Augusto Buzian Brasil ◽  
Carolina Colaço ◽  
Tomas Barrese ◽  
Roberto P. Paes ◽  
Cristina Bortolheiro ◽  
...  

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 12516-12516
Author(s):  
S. Manfrida ◽  
G. R. D’Agostino ◽  
C. Anile ◽  
G. Mantini ◽  
G. Colicchio ◽  
...  

12516 Background: We retrospectively evaluate the tolerance and the efficacy of a conventional schedule of radiotherapy in elderly patients with glioblastoma multiforme (GBM). Methods: Eighty-three consecutive patients affected by glioblastomas were treated between 2001 and 2006. We divided our series in two groups: patients under 65 years (n=52) and patients ≥ 65 years old (n=31). In the elderly group, median age was 68 years (range, 65–80). 17 patients (54,8%) were female, 14 male (45,2%); 20 patients (64,5%) <70 years, 11 patients (35,5%) ≥70 years. Among the younger patients, median age was 51 years (range 25–64), male/female ratio 32/20 (61.5%/38.5%).Twenty-seven out of 31 elderly patients (87,1%) were treated with conformal radiotherapy (CRT, 5940 cGy, 180 cGy/day; CTV2: tumor bed + residual tumor if present + oedema, 3960 cGy; CTV1: tumor bed + residual tumor if present + margins, 1980 cGy). Four out of 31 patients received an intensification dose of xxxx cGy by stereotactic conformal radiotherapy (SRT, 12,9%); among the younger patients, 25/52 were treated with CRT (48,1%) and 27/52 with SRT (51,9%). Concomitant and adjuvant chemotherapy was administered by temozolomide (TMZ).Toxicity was evaluated according to RTOG score. Survival analysis were performed using Kaplan-Meier method and log-rank testing was used for comparison of groups. Results: In the elderly group, neurological acute toxicity was observed in 6/31 patients (19,4%), with grade 3 in two patients. In the under 65 group, 5/52 patients (9,6%) had neurotoxicity (Grade 3 in two patients).This difference was not statistically different.At a median follow-up period of 28 months (range, 3–61), median progression-free survival (PFS) was 11 months in the ≥65 group and 10 months in the under 65 group; median overall survival (OS) was respectively 17 months and 22 months. 1- year survival was respectively 77.6% and 74.5%. Conclusions: In our analysis age did not seem to be a limiting factor in the choice of the therapeutic strategy for patients with glioblastoma multiforme. No significant financial relationships to disclose.


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3490-3490 ◽  
Author(s):  
Marjorie E Zettler ◽  
Chadi Nabhan ◽  
Ajeet Gajra ◽  
Bruce Feinberg

Introduction: Registry data indicate that 20% or more of Hodgkin lymphoma (HL) patients are ≥60; these HL patients have been labeled as elderly as their treatment has been associated with more toxicity, a higher relapse rate, and greater mortality relative to younger patients. The characteristics of HL in elderly patients differ from those in younger patients and may represent a biologically more aggressive disease. Further, elderly patients generally have a greater comorbidity burden than their younger counterparts, which may contribute to their under-representation in clinical trials. Nivolumab (NIVO) and pembrolizumab (PEMBRO) are both approved for treating relapsed/refractory HL based on studies that largely enrolled younger patients, as only about 10% of enrolled patients in the pivotal trials that led to their United States (US) Food and Drug Administration (FDA) approval were ≥60 years of age. Whether adverse events (AEs) related to these immunotherapies differ between younger and older HL patients is unknown and may have important clinical and practice implications. Therefore, we reviewed all post-marketing case reports from the FDA Adverse Events Reporting System (FAERS) Database involving NIVO or PEMBRO for HL and compared AEs and outcomes by age. Methods: The FAERS database is a repository of anonymized reports for product-related AEs, classified using the Medical Dictionary for Regulatory Activities (MedDRA) and categorized as serious or non-serious. The database was queried for cases involving NIVO or PEMBRO (and their respective trade names) from the FDA approval date for the HL indication (May 17, 2016 for NIVO; March 14, 2017 for PEMBRO) through March 31, 2019. Cases were excluded if the age of the patient was unknown, or if the case was reported outside the US. Comparisons of rates of AEs by age group were made using Fisher's exact test; statistical significance was determined at a two-sided α=0.05. Results: A total of 126 cases were retrieved (117 involving NIVO, 9 involving PEMBRO). One hundred and fourteen of the 126 cases (90%) were categorized as serious. Median age of all patients involved was 56 (range 10-89); 53 of the cases (42%) involved patients age 60 or older (Table). Overall, 8 cases had an outcome categorized as life-threatening; 20 cases resulted in death; 2 resulted in disability; and 74 resulted in hospitalization. A higher proportion of cases involving younger patients were categorized under the reaction group "neoplasms benign, malignant and unspecified" (16% vs. 2%; p&lt;0.01), and older patients had a greater incidence of infectious complications compared with their younger counterparts, though this was marginally significant (40% vs. 23%; p=0.05). The proportion of cases resulting in hospitalization was significantly higher in the ≥60 age group as compared to the &lt;60 age group (79% vs. 44%; p &lt;0.01). Adverse reactions that were common in clinical trials, such as fatigue, pyrexia, headache, peripheral neuropathy, upper respiratory tract infection, hypothyroidism, diarrhea, nausea and vomiting, did not show any significant associations by age group (all p values &gt;0.05). Conclusions: Although elderly patients comprise 20% of the HL patient population in the US, our post-marketing analysis indicates that AEs in this subgroup account for more than 40% of the total. This suggests that elderly HL patients experience a disproportional number of AEs compared to younger HL patients. While the types of AEs reported in post-marketing cases generally paralleled those observed in clinical trials of HL patients receiving NIVO or PEMBRO, hospitalizations and infections were more common in the elderly group. These differences in the adverse reactions and safety outcomes associated with PD-1 blockade therapy in HL patients may help inform clinical care and monitoring for AEs. Despite the inherent limitations of this study, our findings complement clinical trial safety data and provide insight into real-world trends in reported safety signals that merit further study. Disclosures Zettler: Cardinal Health: Employment. Nabhan:Aptitude Health: Employment. Gajra:Cardinal Health: Employment. Feinberg:Cardinal Health: Employment.


2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 108-108 ◽  
Author(s):  
Akihiro Ohba ◽  
Atsuo Takashima ◽  
Takamasa Nishiuchi ◽  
Yoshitaka Honma ◽  
Satoru Iwasa ◽  
...  

108 Background: Survival benefits of second-line chemotherapy such as weekly paclitaxel (wPTX) for patients with advanced gastric cancer (AGC) were shown in several phase 3 trials. However, these trials included a small proportion of elderly patients, and few elderly patients receive second-line therapy in clinical practice. The aim of this study was to compare the efficacy and safety of second-line chemotherapy with wPTX between elderly and non-elderly patients. Methods: The subjects of this retrospective study were AGC patients who received wPTX as second-line chemotherapy between January 2002 and August 2014, fulfilling the following selection criteria; 1) pathologically proven metastatic or recurrent gastric adenocarcinoma, 2) receipt of wPTX after platinum or fluoropyrimidine containing chemotherapy. Patients were divided into two groups by age: ≥ 75 years old (elderly group) and < 75 years old (non-elderly group). Response rate (RR) in patients with measurable lesions, overall survival (OS), progression-free survival (PFS), post-progression survival (PPS) and adverse events were evaluated. Hazard ratios of survival were adjusted by prognostic factors using Cox proportional hazard model. Results: A total of 272 patients, 31 elderly and 241 non-elderly, were selected in this study. RRs were 6.2% (1/16) in the elderly group and 12.7% (15/118) in the non-elderly group (p = 0.69). While PFS was similar between two groups (median 2.4 vs. 3.6 months, adjusted hazard ratio [HR] 1.18, p = 0.46), the elderly group showed shorter OS than the non-elderly group (median 5.1 vs. 6.1 months, adjusted HR 1.49, p = 0.06), associated with relatively shorter PPS (median 2.2 vs. 2.6 months, adjusted HR 1.40, p = 0.11). There were no remarkable differences in the incidences of grade 3 or higher adverse events between the two groups (hematologic 38.7 vs. 41.1%; non-hematologic 25.8 vs. 23.7%). No treatment related deaths were observed in either group. Third-line chemotherapy was administered in 19.4% of elderly group and 35.3% of non-elderly group (p = 0.11). Conclusions: It is suggested that second-line chemotherapy with wPTX for AGC may be tolerable and have some clinical benefits for elderly patients as well as for non-elderly patients.


Author(s):  
Hua Zhao ◽  
Jin Zhu ◽  
Yin-da Tang ◽  
Lin Shen ◽  
Shi-ting Li

Abstract Objective The aim of the present study was to evaluate the efficacy and safety of microvascular decompression (MVD) for primary hemifacial spasm (HFS) in patients aged ≥70 years and to compare the outcome with a control cohort of younger patients(<70 years). Methods In this retrospective study, subjects were divided into two groups: an elderly group (patients who were ≥70 years) and a younger group. We compared demographic and clinical data, surgical outcome, MVD-related complications, and duration of operation and hospitalization after MVD between the two groups. Results At a mean follow-up of 32 ± 4.2 months, 188 elderly patients (90.4%) reported an effective outcome without need for any medication versus 379 (91.1%) of the younger cohort. There was no mortality in both cohorts. The prevalence of delayed facial palsy was 4.8% in the elderly group and 4.1% in the younger group. One (0.5%) patient in the elderly group and 3 (0.7%) patients in the younger group suffered cerebrospinal fluid (CSF) leakage. There was no significant difference between the two groups in terms of MVD-related complications, such as delayed facial palsy, hearing impairment, CSF leakage, and hematoma. Conclusions MVD is an effective treatment option in elderly patients with HFS as well as in younger patients. Age itself seems to be no relevant contraindication or, alternatively, risk factor regarding MVD.


2015 ◽  
Vol 123 (1) ◽  
pp. 31-38 ◽  
Author(s):  
Jackson A. Gondim ◽  
João Paulo Almeida ◽  
Lucas Alverne F. de Albuquerque ◽  
Erika Gomes ◽  
Michele Schops ◽  
...  

OBJECT With the increase in the average life expectancy, medical care of elderly patients with symptomatic pituitary adenoma (PA) will continue to grow. Little information exists in the literature about the surgical treatment of these patients. The aim of this study was to present the results of a single pituitary center in the surgical treatment of PAs in patients > 70 years of age. METHODS In this retrospective study, 55 consecutive elderly patients (age ≥ 70 years) with nonfunctioning PAs underwent endoscopic transsphenoidal surgery at the General Hospital of Fortaleza, Brazil, between May 2000 and December 2012. The clinical and radiological results in this group were compared with 2 groups of younger patients: < 60 years (n = 289) and 60–69 years old (n = 30). RESULTS Fifty-five patients ≥ 70 years of age (average age 72.5 years, range 70–84 years) underwent endoscopic surgery for treatment of PAs. The mean follow-up period was 50 months (range 12–144 months). The most common symptoms were visual impairment in 38 (69%) patients, headache in 16 (29%) patients, and complete ophthalmoplegia in 6 (10.9%). Elderly patients presented a higher incidence of ophthalmoplegia (p = 0.032) and a lower frequency of pituitary apoplexy before surgery (p < 0.05). Tumors with cavernous sinus invasion were treated surgically less frequently than in younger patients. Although patients with an American Society of Anesthesiologists score of 3 were more common in the elderly group (p < 0.05), no significant difference regarding surgical time, extent of resection, and hospitalization were observed. Elderly patients presented with more complications than patients < 60 years (32.7% vs 10%, p < 0.05). Complications observed in the elderly group included 5 CSF leaks (9%), 2 permanent diabetes insipidus cases (3.6%), 4 postoperative refractory hypertension cases (7.2%), 1 myocardial ischemia (1.8%), and 1 death (1.8%). Postoperative new anterior pituitary deficit was more common in the younger group (< 60 years old: 17.7%) than in the elderly (≥ 70 years old: 12.7%); however, there was no statistical difference. CONCLUSIONS Endoscopic transsphenoidal surgery for elderly patients with PAs may be associated with higher complication rates, especially secondary to early transitory complications, when compared with surgery performed in younger patients. Although the worst preoperative clinical status might be observed in this group, age alone is not associated with a worst final prognosis after endoscopic removal of nonfunctioning PAs.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 33-33
Author(s):  
Philip A Haddad ◽  
Dalia Hammoud ◽  
Kevin M. Gallagher

Introduction: Mantle cell lymphoma (MCL) is an incurable B-cell malignancy that disproportionately affects the elderly. After first-line therapy failure, relapsed/refractory MCL assumes a more aggressive and universally fatal course. Currently, several classes of chemo/biologic therapies are approved in the second line. However, these agents and their combinations have not been compared head-to-head. We conducted this proportional meta-analysis to evaluate their relative impact on selected clinical outcomes. Methods: A review of the medical literature was conducted using online databases. Inclusion criteria consisted of English language; diagnosis of relapsed/refractory MCL; trials that explored the efficacy of first-line approved antineoplastic agents and their combinations that comprised: BTK-inhibitors (Ibrutininb (IB), Acalabrutinib, Zanubrutinib), Bortezomib (Velcade, VEL), Venetoclax (VEN), Lenalidomide (LEN), and Bendamustine+Rituximab (B-R); and studies reporting types of responses and duration of response. Proportional meta-analysis was conducted using random-effects model. The respective 95% confidence intervals were calculated, and funnel plots were constructed. Results: Thirteen studies comprising a total of 1,264 participants were included. The pooled overall response rates, ORR (95%CI), of the regimens were: 74% (66,81) BTK-inhibitors, 39% (25,53) VEL, 34% (24,46) LEN, 85% (78,92) B-R, 75% (58,92) VEN-IB, and 88% (79,97) IB-R. The pooled complete responses, CR (95%CI), of the regimens were: 33% (20,47) BTK-inhibitors, 9% (5,13) VEL, 6% (4,9) LEN, 45% (36,54) B-R, 42% (22,63) VEN-IB, and 44% (30,58) IB-R. There were no significant differences in ORR and CR between BTK-inhibitors, B-R, VEN-IB, and IB-R. ORR of VEL and LEN also did not significantly differ. However, ORR and CR of the former group were significantly higher than those of the latter. The pooled partial responses, PR (95%CI), of the regimens were: 41% (32,50) BTK-inhibitors, 28% (20,38) VEL, 28% (15,43) LEN, 41% (35,47) B-R, 34% (15,53) VEN-IB, and 44% (30,58) IB-R. There were no significant differences between PR of the regimens. The weighted duration of responses in months, DOR (95%CI), of the regimens were: 20 BTK-inhibitors, 9 VEL, 16 LEN, and 20 B-R. Conclusions: This proportional meta-analysis is the first to compare the current regimens in first-line relapsed/refractory MCL. It indicates that BTK-inhibitors monotherapy, IB combinations with R or VEN, and B-R provide equivalent ORR and CR rates that are significantly better than VEL and LEN with notably longer duration of response. It also raises questions about whether there is an additional ORR and CR benefits when adding VEN or R to IB in this clinical setting. Disclosures No relevant conflicts of interest to declare.


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