Prediction of Poor Outcome in Older Patients Receiving Chemotherapy for Malignant Lymphoma: A New Frailty Scoring

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2353-2353
Author(s):  
Stephanie Dubruille ◽  
Cindy Kenis ◽  
Yves Libert ◽  
Michel Delforge ◽  
Catherine Choffray ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Board Of Directors ◽  
Older Patients ◽  
Causes Of Death ◽  
Functional Decline ◽  
Advisory Committees ◽  
Frail Patients ◽  
Vulnerable Patients ◽  
To Receive ◽  
Frailty Score

Abstract Introduction: Patients "clinically fit" to receive chemotherapy suffering from malignant hemopathies, are an heterogeneous population covering fit and vulnerable patients. Patients with geriatric syndromes and/or irreversible comorbidities are usually excluded from high dose chemotherapy. However, a reliable "frailty score" remains urgently needed to better define the vulnerable population that does not benefit from chemotherapy. In the literature, two clinical (functional decline and Mild Cognitive Impairment (MCI)) and two biological (anemia and inflammation) factors are frequently correlated with poor overall survival (OS) or chemotherapy-related toxicity. Objective: To determine a clinico-biological tool for the screening of vulnerable patients with malignant hemopathies presenting unacceptable chemotherapy-related toxicity or disappointing result defined as a poor OS. Methods: This prospective multicentric study was conducted in the institute 'Jules Bordet' (Brussels) and in the University Hospitals of Leuven (Leuven). A Comprehensive Geriatric Assessment (CGA) was performed to 251 consecutive patients (65-90yrs) with malignant hemopathies admitted to receive chemotherapy. Clinical data, biological parameters and causes of death were extracted from medical records. A screening tool composed of 0 to 4 of the prognostic factors (loss of functional autonomy (Activities of Daily Living scale [ADL]), MCI (Mini Mental State Examination [MMSE]), anemia [hemoglobin] and inflammation [CRP]) was applied to our population. Univariate and multivariate Cox proportional hazards model were used to predict OS. Results: One hundred and eighty two patients were evaluable for all characteristics (NHL, n=105; CLL, n=20; MM, n=26; AML, n=17; ALL, n=6; LMMC, n=3, MDS, n=5). Eighty-three percent had a more favorable prognosis (NHL, CLL or MM) and fifty-five percent have a first diagnosis of cancer. A "frailty" scoring system (range 0-4) was developed, based on items we identified as predictive factors: functional decline (ADL<6, n=94), Mild Cognitive Impairment (MCI) (MMSE<27, n=51), anemia (HB<11g/dl, n=90) and inflammation (CRP≥2mg/l, n=149). The population was stratified into 3 groups: fit (score=0-1, n=56), vulnerable (score= 2, n=60) and "frail" (score= 3 or 4, n=66). The OS was 86% in fit, 60% in vulnerable (hazard ratio (HR)=3.29; 95% CI=1.48-7.33; P=.004) and 41% in "frail" patients (HR=5.87; 95% CI=2.74-12.59; P<.001). Causes of death remain disease-related in a majority of the patients (82%). In our largest group of older patients (NHL, n=105), the frailty scoring was also applied (ADL<6, n=48; MMSE<27, n=29; HB<11g/dl, n=36; CRP≥2mg/l, n=85): the OS was 87% in fit (n=45), 65% in vulnerable (n=31) (HR=2.94; 95% CI=1.11-7.96; P=.034) and 41% in "frail" patients (n=29) (HR=6.61; 95% CI=2.60-16.83; P<.001) and thus reliable in this specific population. Conclusions: In our selected population of patients with malignant hemopathies and particularly in the group of NHL, "clinically fit" to receive chemotherapy, our "frailty score" helps clinician to predict a poor OS. This scoring detects unsuspected "frail" patients who may benefit from palliative care. Further prospective analyses in a larger population, are on going to refine the score in other malignant hemopathies in order to avoid overtreatment in these vulnerable older patients. Disclosures Maerevoet: roche: Membership on an entity's Board of Directors or advisory committees; ARGN-X: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Cognitive Impairment, Hypoalbuminemia, High CRP Level and Past History of Gastro-Intestinal Ulcer: 4 Markers of Frailty Which Identify Older Patients with Malignant Hemopathies Who Shouldn't Benefit from Chemotherapy

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4756-4756
Author(s):  
Stephanie Dubruille ◽  
Cindy Kenis ◽  
Vincent Thibaud ◽  
Yves Libert ◽  
Michel Delforge ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Function ◽  
Older Patients ◽  
Functional Decline ◽  
Albumin Level ◽  
Poor Survival ◽  
Frail Patients ◽  
One Year ◽  
To Receive ◽  
Frailty Score

Abstract INTRODUCTION: Major progresses have been achieved to identify older patients with malignant hemopathies who should be treated with standard doses of chemotherapy. However, a reliable frailty score remains urgently needed to better define the unsuspected vulnerable population that does not benefit from chemotherapy. In the literature, three clinical (functional decline, cognitive impairment (CI) and comorbidities) and two biological (low albumin level and high IL-6 level) factors are frequently associated with a poor overall survival (OS) and/or chemotherapy-related toxicities. OBJECTIVE: To investigate the reliability of a simple clinico-biological tool for the screening of frail patients with malignant hemopathies to predict a poor survival (<6 months). METHODS: 285 consecutive patients (65-90yrs) with malignant hemopathies admitted to receive chemotherapy where included in a prospective multicentric study conducted in the Inst. J. Bordet (ULB, Brussels) and in the University Hospitals Leuven (KU, Leuven). A Comprehensive Geriatric Assessment (CGA) was performed. Univariate and multivariate Cox proportional hazards models were used to evaluate the value of functional decline, abnormal cognitive function, comorbidities, low albumin and CRP level to predict 1-year survival. RESULTS: One hundred and ninety-two patients were evaluable for the clinico-biological screening tool (NHL, n=111; CLL, n=19; MM, n=29; AML, n=20; ALL, n=3; LMMC, n=7; MDS, n=3). Eighty-three percent were considered to have a more favorable prognosis (NHL, CLL or MM). Functional decline was associated with abnormal cognitive function (P=0.029) and inflammation (P=0.002). Based on our previous analyses in the Charlson Comorbidity Index we took the strongest prognostic factor: gastro-intestinal (GI) ulcer (P=0.001). A "frailty" scoring system was thus developed, based on our 4 independent predictive factors for poor survival: CI (MMSE<27, n=57), presence of GI ulcer (n=29), low albumin level (alb<3.5g/dl, n=57) and surrogate marker of IL-6 level (CRP≥2mg/l, n=146). The population was stratified into 3 groups: "fit" (score=0-1, n=102), "vulnerable" (score=2, n=58) and "frail" (score=3-4, n=32). The one-year survival was 80% in "fit" and 53% in "vulnerable" patients (HR=2.75; 95% CI=1.54-4.91; P=.001). In "frail" patients 38% were alive at one-year (HR=4.87; 95% CI=2.61-9.09; P<.001) with a median survival of 5 months. Causes of death remain disease-related in a majority of the patients (69%). CONCLUSIONS: In our selected population of "clinically fit patients" referred to receive chemotherapy for malignant hemopathies, our frailty score helps the clinician to predict a very poor outcome. This frailty score detects unsuspected frailty in patients who may benefit from palliative care. Ongoing prospective analyses in a larger cohort of malignant hemopathies will be updated to validate the reliability of this score. Disclosures Delforge: Amgen, Celgene, Janssen and Takeda: Consultancy; Celgene and Janssen: Research Funding.

scholarly journals The Combination of Frailty and ISS Scores Identifies a Simple Prognostic Index for Overall Survival in Elderly Patients Treated with Novel Agents-Based Induction Therapy

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4740-4740
Author(s):  
Alessandra Larocca ◽  
Sara Bringhen ◽  
Roman Hajek ◽  
Maria Teresa Petrucci ◽  
Massimo Offidani ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Board Of Directors ◽  
Research Funding ◽  
Dose Intensity ◽  
Staging System ◽  
Advisory Committees ◽  
Frail Patients ◽  
International Staging System ◽  
Frailty Score

Abstract Background: Several biological parameters define patients with multiple myeloma (MM) at high-risk of progression or death. The well-known International Staging System (ISS), as well as age per se, are insufficient to explain differences of overall survival (OS) in patients over 65 years, who are 2/3 of newly diagnosed (ND) MM patients. We have recently showed that a frailty score combining age, functional status (Activity of Daily Living and Instrumental Activity of Daily living scores) and comorbidities (Charlson index) defines 3 categories of patients - fit, intermediate-fitness, frail - with significantly differences in OS and progression-free survival (Larocca A, et al. Blood 2013 122:687). Here we assess the causes of the different mortality in intermediate-fitness and frail groups compared to fit ones and present a final prognostic score based on the combination of ISS and frailty scores. Methods: NDMM patients over 65 years enrolled in 3 clinical trials, receiving either lenalidomide, bortezomib or carfilzomib were included in the analysis. Details on treatment regimens and results of these studies have previously been reported (Palumbo A, et al. Blood 2013 122:536; Larocca A, et al. Blood 2013 122:539, Bringhen S et al. Blood 2014 Jul 3;124(1):63-9). The cumulative incidences of discontinuation and toxicities were calculated using the Fine & Gray model. The frailty score was combined with ISS with the CHi-squared Automatic Interaction Detector method used as an iterative decision tree. Results: 869 patients (median age 74 years) were included in the analysis; 260 (30%) were frail, 269 (31%) intermediated-fitness and 340 (39%) fit. The 3-year OS was 57% in frail, 76% in intermediated-fitness and 84% in fit patients. Overall, 143 patients (16%) died, 70 (27%) frail, 39 (14%) intermediate-fitness and 34 (10%) fit. The causes of death were: disease progression [35 (13%) in frail, 22 (8%) in intermediate-fitness and 18 (5%) in fit patients] and toxicity [21 (8%), 10 (4%) and 11 (3%), respectively]. The higher risk of death for progression was related with the lower dose-intensity due to the higher rate of drug discontinuation and/or dose reduction. The average dose intensity was lower in frail (74%, p=0.0006) and intermediate-fitness patients (80%, p=0.07) compared with fit patients (85%). The cumulative incidence of drug discontinuation for any cause, excluding progression and death, was higher in frail (25%; HR 2.21, p<0.001) and intermediate-fitness (22%; HR: 1.41, p=0.052) patients compared with fit ones (17%). The most frequent reasons for toxicity-related death were cardiac events [11 (4%) in frail patients, 2 (1%) in intermediate-fitness, 3 (1%) in fit] and infections [8 (3%), 2 (1%) and 2 (1%), respectively]. When we combined the frailty score with the ISS, 6 groups of patients and 4 risk categories were identified: fit patients with ISS I at low risk (15%; 3-year OS: 94%), fit patients with ISS stage II or III and intermediate-fitness patients with ISS I, II or III at intermediate risk (55%; 3-year OS: 75-77%.), frail patients with ISS stage I or II at high risk (19%; 3-year OS: 61%) and frail patients with ISS stage III at very-high risk (11%, 3-year OS: 55%) (Figure 1). Conclusion: The inferior survival observed among intermediate-fitness and in frail patients as compared to fit ones, is related to a higher rate of toxic deaths and disease progression, due to a lower dose intensity. The combination of the frailty score, evaluating the patient's status, and the standard ISS, taking into account the biological characteristics of the disease, can predict survival and enhances the single predictive values of the scores, thus representing a valuable tool for treatment-decision in the clinical practice. Figure 1. Overall survival of patients classified into 6 categories according to the recursive partitioning analysis by combining the frailty score and the International Staging System. Figure 1. Overall survival of patients classified into 6 categories according to the recursive partitioning analysis by combining the frailty score and the International Staging System. Disclosures Larocca: Janssen Cilag: Honoraria; Celgene: Honoraria. Off Label Use: Use off-label of lenalidomide (immunomodulatory drug), carfilzomib (proteasome inhibitor), subcutaneous bortezomib (proteasome inhibitor) in terms of schedule used and combination.. Bringhen:Onyx: Consultancy; Merck Sharp & Dohme: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; Janssen and Cilag: Honoraria; Celgene: Honoraria. Hajek:Janssen: Honoraria; Celgene: Consultancy, Honoraria; Merck: Consultancy, Honoraria. Offidani:Celgene: Honoraria; Janssen: Honoraria. Maracci:Mundipharma: Honoraria. Gay:Sanofi: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Marasca:Janssen: Honoraria; Celgene: Honoraria. Giuliani:Celgene: Research Funding. Musto:Janssen: Honoraria; Celgene: Honoraria. Boccadoro:Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Onyx: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees. Sonneveld:Millenium: Honoraria, Research Funding; Onyx: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Palumbo:Celgene: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria; Millennium Pharmaceuticals, Inc.: Consultancy, Honoraria; Onyx Pharmaceuticals: Consultancy, Honoraria; Array BioPharma: Honoraria; Amgen: Consultancy, Honoraria; Sanofi: Honoraria; Genmab A/S: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria.

scholarly journals Ixazomib and Daratumumab without Dexamethasone (I-Dara) in Elderly Frail RRMM Patients. a Multicenter Phase 2 Study (IFM 2018-02) of the Intergroupe Francophone Du Myélome (IFM)

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 83-83
Author(s):  
Magaret Macro ◽  
Cyrille Touzeau ◽  
Clara Mariette ◽  
Salomon Manier ◽  
Sabine Brechignac ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Progressive Disease ◽  
Response Rate ◽  
Phase 2 ◽  
Advisory Committees ◽  
Frail Patients ◽  
Phase 2 Study ◽  
Grade 3 ◽  
Frailty Score

Abstract Purpose: Frail patients with multiple myeloma have an inferior outcome, especially in the relapse setting. This adverse prognosis is mainly related to a high discontinuation rate due to treatment related adverse events. The aim of this phase 2 study is to evaluate efficacy and tolerability of Ixazomib-Daratumumab (I-Dara) without Dexamethasone in elderly frail patients with relapsed myeloma (NCT03757221). Methods: Fifty Ixa-Dara naïve RRMM patients (1-2 prior therapy) were planned to receive oral Ixa (4 mg: days 1, 8, 15), IV Dara (16 mg/kg; days 1, 8, 15, 22, cycles 1-2; days 1, 15, cycles 3-6; days 1, cycles 7+) and IV Methylprednisolone before Dara (100 mg at day 1, 8, cycle 1 and then 60 mg). They were enrolled if frailty score was ≥2 by IMWG score and FIRST proxy score (Facon T et al, Leukemia, 2020). The primary endpoint was ≥very good partial response rate at one year. Secondary endpoints included ORR, PFS, OS & toxicity according to NCI-CTCAE version 5.0. Results: Among 52 patients screened during this ongoing trial, 44 were included between 03/2018 and 05/2021. Patient were at first (n=28) or second relapse (n=16). Thirty -eight patients (86%) were previously exposed to bortezomib and 8 (18%) were previously refractory to lenalidomide. Median age was 82 (80-84). All patients had a frailty score ≥2. In 22 patients ISS was stage I (n=5), II (n=10) or III (n=7). Eleven (32%) patients harbored high-risk cytogenetic, including t(4;14) (n=3) or del17p (n=8). The median duration of Tx among 23 pts with ongoing Tx was 6 months [0-27] at data cutoff (July 19)]. The median duration of Tx among 21 pts who stopped Tx was 7 months [0-21]: 13 had progressive disease. Six patients died during the study: Daratumumab-related bronchospasm (D1C1); Ixazomib-related overdose (C2); progressive disease (C2 & C4), sepsis (C1 & C2). Regarding toxicity, 28 ≥grade 3 AE occurred amongst 24 pts (54%). The most common grade 3-4 toxicities were thrombocytopenia (n=5), other cytopenias (n=4), infection (n=4) and gastrointestinal disorders (n=2). Fourteen out of 28 were SAE including 1 bronchospasm, 1 acute respiratory failure and 2 ixazomib overdoses. Overall response rate, including minimal response, was 86 % in pts with ongoing treatment and 71% in pts who stopped Tx; ≥VGPR rate was 33% and 6% respectively. Conclusions: These preliminary results show a favorable safety profile of ixazomib and daratumumab combination, without dexamethasone, in this specific population of very elderly frail patients with RRMM and high risk cytogenetic for almost one third of them. Efficacy results will be analyzed when the 50 patients will be enrolled in the study and evaluable for the primary endpoint. Disclosures Macro: GSK: Honoraria; Sanofi: Honoraria; Celgen/BMS: Honoraria; Janssen: Honoraria, Other: Travel accomodation, Research Funding; Takeda: Honoraria, Other: Travel accomodation, Research Funding. Manier: Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotechnologies: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Regeneron: Consultancy, Research Funding; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene - Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Vincent: Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Decaux: Amgen BMS Celgene Janssen Sanofi Takeda: Honoraria. Leleu: Bristol-Myers Squibb: Honoraria; Carsgen Therapeutics Ltd: Honoraria; Celgene: Honoraria; Gilead Sciences: Honoraria; Janssen-Cilag: Honoraria; Karyopharm Therapeutics: Honoraria; Merck: Honoraria; Mundipharma: Honoraria; Novartis: Honoraria; Oncopeptides: Honoraria; Pierre Fabre: Honoraria; Roche: Honoraria; Sanofi: Honoraria; Amgen: Honoraria; AbbVie: Honoraria; Takeda: Honoraria, Other: Non-financial support. OffLabel Disclosure: Ixazomib and Daratumumab association is not approved in NDMM or in RRMM

Measurement and Prevalence of Cognitive Impairment in Older Patients with Hematologic Malignancies

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 689-689 ◽  
Author(s):  
Tammy T. Hshieh ◽  
Nolan B. Condron ◽  
Richard M. Stone ◽  
Robert J. Soiffer ◽  
Gregory A. Abel
Keyword(s):  
Cognitive Impairment ◽  
Grip Strength ◽  
Board Of Directors ◽  
Gait Speed ◽  
Older Patients ◽  
Hematologic Malignancy ◽  
Cognitively Impaired ◽  
Advisory Committees ◽  
Delayed Recall ◽  
Cumulative Deficit

Abstract Background:Little is known about the frequency of cognitive impairment in older patients with blood cancers, nor how such impairment may contribute to their overall frailty. Understanding the prevalence of impairment is specifically important for this population, because intact cognition is needed to make complex medical decisions, including whether to pursue intensive treatments versus supportive care. We report data from the Older Adult Hematologic Malignancy (OHM) clinic at the Dana-Farber Cancer Institute, which routinely screens patients 75 or older for frailty using tools that incorporate subjective and objective measures of cognition. Methods: Since February of 2015,all patients aged 75 and older who present for initial consultation for hematologic malignancy have been approached for evaluation by a trained clinic assistant. In a 15-minute interview, the assistant uses two parallel methods of screening to characterize the patient as frail, pre-frail or robust. The first employs a "cumulative deficit" approach (Rockwood, 2007) including a 26-item questionnaire adapted from theYale Precipitating Events Project (Searle, 2008), a grip strength test (Gill, 2006), gait speed test (Studenski, 2011), delayed recall section of the Montreal Cognitive Assessment (MOCA; Nasreddine, 2005) and the Clock In Box test, a cognitive impairment screening tool (CIB; Chester, 2011). The second uses a "phenotypic" approach (Fried, 2001), which gives equal weight to the gait speed and grip strength tests, plus three questions about weight loss, energy expenditure and self-reported exhaustion. We also assess two subjective measures of cognition: (1) whether the patient knows why s/he is presenting to the hospital and (2) whether s/he needs help filling out the questionnaire. Results: As of July 1, 2016, 235 of 275 patients approached (85%) agreed to be assessed. Median age was 78 years and 37% were female; 32% were seen in the leukemia clinic, 37% in the lymphoma clinic and 31% in the myeloma clinic. More patients were determined to be definitively frail or robust by the cumulative deficit approach compared with the phenotypic approach, which categorized the majority of patients as pre-frail (Table 1). With respect to cognition, 35.4% of the cohort was found to have probable impairment and 27.3% possible impairment by CIB (Table 2). Fewer patients were found to have probable impairment (18.0%) and possible impairment (19.8%) by MOCA delayed recall. Overall, 18.5% of robust patients had possible or probable cognitive impairment by CIB, and 9.5% by MOCA delayed recall. Nearly 7% of the patients could not explain why they were presenting to the hospital; all of these patients also had probable cognitive impairment and were pre-frail or frail. Moreover, 17% of the total cohort needed assistance completing the questionnaire; half of these had probable cognitive impairment, 43% had possible impairment, and most (92.5%) were pre-frail or frail. The odds of being pre-frail or frail (phenotypic) if cognitively impaired per CIB was 1.89 (95% CI 1.073.34; p=0.03). The odds of being pre-frail or frail (phenotypic) if cognitively impaired per MOCA delayed recall was 1.86 (95% CI 1.02-3.40; p=0.04). Conclusions: Cognitive impairment was prevalent in this cohort of older patients with blood cancers, with between one- to two-thirds of patients testing as probably or possibly impaired using standard measures.A portion of patients who were robust per the brief phenotypic frailty screen were also cognitively impaired, which suggests routinely performing comprehensive frailty screening (cumulative deficit) or adding a cognitive measure such as the CIB. Compared to the phenotypic approach, the cumulative deficit approach, which incorporates specific measurement of cognitive impairment, seemed to result in further discriminaton between patients who were frail versus robust. The CIB test detected more cognitive impairment than the MOCA delayed recall, likely because it assesses both executive function and working memory, whereas the MOCA delayed recall only tests the latter. Taken together, our data suggest that cognitive impairment likely contributes significantly to overall frailty for older patients with blood cancers, and argue for routine testing for such impairment in this patient population. Disclosures Stone: Amgen: Consultancy; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jansen: Consultancy; Seattle Genetics: Consultancy; Celator: Consultancy; Agios: Consultancy; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy; Novartis: Consultancy; Pfizer: Consultancy; ONO: Consultancy; Juno Therapeutics: Consultancy; Merck: Consultancy; Roche: Consultancy; Sunesis Pharmaceuticals: Consultancy; Xenetic Biosciences: Consultancy. Soiffer:Kiadis: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Juno: Membership on an entity's Board of Directors or advisory committees.

scholarly journals 160 The Effect of Frailty and COVID-19 Infection on Clinical Outcomes in Older Adults—A Single Centre Retrospective Study

2021 ◽  
Vol 50 (Supplement_1) ◽  
pp. i12-i42
Author(s):  
O Okuwoga ◽  
S Mufti
Keyword(s):  
Older Patients ◽  
Single Centre ◽  
Clinical Frailty Scale ◽  
Health Records ◽  
Frail Patients ◽  
Nice Guidance ◽  
Data Points ◽  
Continued Use ◽  
Support Decision Making ◽  
Frailty Score

Abstract Introduction It was anticipated that the COVID-19 pandemic would put a strain on our healthcare system, disproportionately affecting older people. NICE guidance recommended using frailty scoring to support decision making around escalation of care. This study aimed to assess frailty, demographics and COVID-19 infection and to investigate how these related to outcomes of patients aged over 65 years admitted to hospital. Methods A single centre retrospective cohort study was carried out by reviewing the electronic health records of all admissions over 65 years. Data points collected included length of stay (LOS), frailty score using the Rockwood Clinical Frailty Scale (CFS) and mortality. Patients were stratified into COVID and non-COVID based on health records and into non-frail (CFS 1–4) and frail (CFS 5–9). Results A total of 257 patients admitted between 30th March and 30th April 2020 were included in the study (mean age 79 years, 43% female). 141 (54.9%) of patients were diagnosed with COVID-19 infection. 120 patients had CFS 1–4 and 136 has CFS 5–9. 1 patient did not have a frailty score due to insufficient information. 68 (26.8%) of all patients died during the admission. The relative risk (RR) of mortality of patients with coronavirus was 6.3 (95% CI 3.1–12.6, p &lt; 0.0001). The RR of mortality for frail patients compared to the non-frail was 2.1 (95% CI 1.3–3.2, p = 0.002). The median LOS for patients with COVID-19 was 5 days, compared to 4 days for patients who did not have coronavirus. Frailty did not predict longer admission, with median LOS of 5 days for both non-frail and frail patients. Conclusion The results demonstrated in this study show that COVID-19 infection and frailty were significantly associated with increased mortality in older patients. This validates the continued use of frailty scoring of older patients on admission to support care planning.

scholarly journals Treatment Patterns and Outcomes in Elderly Patients with Newly Diagnosed Multiple Myeloma: Results from the Connect® MM Registry

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3129-3129
Author(s):  
Hans C. Lee ◽  
Sikander Ailawadhi ◽  
Cristina Gasparetto ◽  
Sundar Jagannath ◽  
Robert M. Rifkin ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Causes Of Death ◽  
Age Groups ◽  
Treatment Patterns ◽  
Age Group ◽  
Newly Diagnosed ◽  
Employment Equity ◽  
Advisory Committees ◽  
Equity Ownership

Background: Multiple myeloma (MM) is common among the elderly, with 35% of patients (pts) diagnosed being aged ≥75 years (y). With increasing overall life expectancy, the incidence and prevalence of newly diagnosed and previously treated MM patients ≥80 y is expected to increase over time. Because elderly pts are often excluded from clinical trials, data focused on their treatment patterns and clinical outcomes are lacking. The Connect® MM Registry (NCT01081028) is a large, US, multicenter, prospective observational cohort study of pts with newly diagnosed MM (NDMM) designed to examine real-world diagnostic patterns, treatment patterns, clinical outcomes, and health-related quality of life patient-reported outcomes. This analysis reviews treatment patterns and outcomes in elderly pts from the Connect MM Registry. Methods: Pts enrolled in the Connect MM registry at 250 community, academic, and government sites were included in this analysis. Eligible pts were adults aged ≥18 y with symptomatic MM diagnosed ≤2 months before enrollment, as defined by International Myeloma Working Group criteria; no exclusion criteria were applied. For this analysis, pts were categorized into 4 age groups: <65, 65 to 74, 75 to 84, and ≥85 y. Pts were followed from time of enrollment to the earliest of disease progression (or death), loss to follow-up, or data cutoff date of February 7, 2019. Descriptive statistics were used for baseline characteristics and treatment regimens. Survival outcomes were analyzed using Cox regression. Time to progression (TTP) analysis excluded causes of death not related to MM. Results: Of 3011 pts enrolled (median age 67 y), 132 (4%) were aged ≥85 y, and 615 (20%) were aged 75-84 y at baseline. More pts aged ≥85 y had poor prognostic factors such as ISS stage III disease and reduced hemoglobin (<10 g/dL or >2 g/dL <LLN) compared with other age groups, although no notable differences between creatinine and calcium levels were observed across age groups (Table). A lower proportion of elderly pts (75-84 and ≥85 y) received triplet regimens as frontline therapy. More elderly pts received a single novel agent, whereas use of 2 novel agents was more common in younger pts (Table). The most common frontline regimens among elderly pts were bortezomib (V) + dexamethasone (D), followed by lenalidomide (R) + D, whereas those among younger pts included RVD, followed by VD and CyBorD (Table). No pt aged ≥85 y, and 4% of pts aged 75-84 y received high-dose chemotherapy and autologous stem cell transplant (vs 61% in the <65 y and 37% in the 65-74 y age group). The most common maintenance therapy was RD in pts ≥85 y (although the use was low) and R alone in other age groups (Table). In the ≥85 y group, 27%, 10%, and 4% of pts entered 2L, 3L, and 4L treatments respectively, vs 43%, 23%, and 13% in the <65 y group. Progression-free survival was significantly shorter in the ≥85 y age group vs the 75-84 y age group (P=0.003), 65-74 y age group (P<0.001), and <65 y age group (P<0.001; Fig.1). TTP was significantly shorter in the ≥85 y group vs the <65 y group (P=0.020); however, TTP was similar among the 65-74 y, 75-84 y, and ≥85 y cohorts (Fig. 2). Overall survival was significantly shorter in the ≥85 y group vs the 75-84 y, 65-74 y, and <65 y groups (all P<0.001; Fig. 3). The mortality rate was lowest (46%) during first-line treatment (1L) in pts aged ≥85 y (mainly attributed to MM progression) and increased in 2L and 3L (47% and 54%, respectively); a similar trend was observed in the younger age groups. The main cause of death was MM progression (29% in the ≥85 y vs 16% in the <65 y group). Other notable causes of death in the ≥85 y group included cardiac failure (5% vs 2% in <65 y group) and pneumonia (5% vs 1% in <65 y group). Conclusions: In this analysis, elderly pts received similar types of frontline and maintenance regimens as younger pts, although proportions varied with decreased use of triplet regimens with age. Considering similarities in TTP across the 65-74 y, 75-84 y, and ≥85 y cohorts, these real-world data support active treatment and aggressive supportive care of elderly symptomatic pts, including with novel agents. Additionally, further clinical studies specific to elderly patients with MM should be explored. Disclosures Lee: Amgen: Consultancy, Research Funding; GlaxoSmithKline plc: Research Funding; Sanofi: Consultancy; Daiichi Sankyo: Research Funding; Celgene: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Ailawadhi:Janssen: Consultancy, Research Funding; Takeda: Consultancy; Pharmacyclics: Research Funding; Amgen: Consultancy, Research Funding; Celgene: Consultancy; Cellectar: Research Funding. Gasparetto:Celgene: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed ; Janssen: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed ; BMS: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed . Jagannath:AbbVie: Consultancy; Merck & Co.: Consultancy; Bristol-Myers Squibb: Consultancy; Karyopharm Therapeutics: Consultancy; Celgene Corporation: Consultancy; Janssen Pharmaceuticals: Consultancy. Rifkin:Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Durie:Amgen, Celgene, Johnson & Johnson, and Takeda: Consultancy. Narang:Celgene: Speakers Bureau. Terebelo:Celgene: Honoraria; Jannsen: Speakers Bureau; Newland Medical Asociates: Employment. Toomey:Celgene: Consultancy. Hardin:Celgene: Membership on an entity's Board of Directors or advisory committees. Wagner:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; American Cancer Society: Other: Section editor, Cancer journal. Omel:Celgene, Takeda, Janssen: Other: Patient Advisory Committees. Srinivasan:Celgene: Employment, Equity Ownership. Liu:TechData: Consultancy. Dhalla:Celgene: Employment. Agarwal:Celgene Corporation: Employment, Equity Ownership. Abonour:BMS: Consultancy; Celgene: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Janssen: Consultancy, Research Funding.

scholarly journals Patient Characteristics and Outcomes in Adolescents and Young Adults (AYA) with Acute Myeloid Leukemia (AML): Princess Margaret Cancer Centre Experience

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2609-2609
Author(s):  
Muhned Alhumaid ◽  
Georgina S Daher-Reyes ◽  
Wilson Lam ◽  
Arjun Law ◽  
Tracy Murphy ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Age Groups ◽  
Treatment Strategies ◽  
Patient Characteristics ◽  
Cancer Center ◽  
Advisory Committees ◽  
Disease Behavior

Introduction: Clinical outcomes of acute myeloid leukemia (AML) in adolescents and young adults (AYA) are rarely reported as an isolated subgroup. Treatments vary little across age groups, and treatment intensity depends upon comorbid conditions and performance status. Optimal treatment strategies focused on disease behavior, biological factors, and the distinct needs of this subset of AML patients remain elusive. The purpose of this retrospective analysis is to determine the characteristics and outcomes of AYA AML patients treated at a specialized adult leukemia cancer center in comparison to older adults with AML (40-60 years). Methods: A retrospective analysis was performed on all patients treated at Princess Margaret Cancer Center from 2008-2018. Patients with acute promyelocytic leukemia were excluded. Clinical characteristics, treatment strategies, and survival outcomes were recorded for all patients. Overall survival (OS) and disease-free survival (DFS) rates were calculated using the Kaplan-Meier product-limit method and the impact of covariates were assessed using the Log-rank test. Finally, we compared the outcomes of AYA patients treated at our centre between 2015-2018 with older patients. Results: A total of 175 patients aged 18-39 were identified. Patient characteristics are shown in (Table 1). Cytogenetic were available in 163 patients. Based on MRC criteria, 27 (16%) were favorable risk, intermediate in 95 (54%), adverse in 39 (22%), and missing/failed in 14(8%). NPM1 status was available in 110 patients of whom 38 (35%) were positive. FLT3-ITD was available in 67 patients with 24 (36%) positive. Both mutations were present in 13 (54%) patients. There were no significant differences in terms of risk stratification based on cytogenetic and molecular markers based on age (18-29 vs.30-39) (P= 0.98). Most patients 172 (98%) received induction, 157 (91%) with 3+7, and 15 (9%) with FLAG-IDA. Complete remission (CR) was achieved in 133 (77%) after first induction [120 (76%) after 3+7 and 11 (73%) after FLAG-IDA]. Induction related mortality was low (2%). Of the 39 who did not achieve CR, thirty-four patients received re-induction (13 FLAG-IDA, 16 NOVE-HiDAC, 5 others) with CR in 21 (62%). Overall, 154 (89.5%) achieved CR1. Sixty-four (42%) proceeded to hematopoietic stem cell transplantation (HSCT) in CR1. 59 (38%) patients relapsed in CR1 with 8 (12%) relapsing post HSCT. Fifty-five (5 post HSCT) patients received reinduction with 30 (51%) (2 after HSCT) achieving CR2. Fifteen patients received HSCT in CR2. OS and DFS at 2 years were 62% (95% CI 0.53-0.69) and 50% (95% CI 0.41-0.57), respectively. Stratified by cytogenetic risk, OS was 81% for favorable risk, 61% for intermediate, and 50% for adverse risk (P=0.0001), respectively. DFS in these groups was 85%, 57%, and 46 % (P=0.0025), respectively. We further compared outcomes in the 18-29y and 30-39y age groups. The OS was 61.9% compared to 62.5% (P=0.91) and DFS of 52.1% compared to 47% (P=0.65) respectively. On univariate analysis for OS and DFS, cytogenetic risk stratification was the only significant variable (P=0.0004 and P=0.0042). We then compared the outcomes 67 sequential patients aged I8-39 treated from 2014-2018, with those of 176 sequential patients aged 40-60 treated during the same period (table 2). OS at 2 years was not statistically higher in the younger group compared to the older group (66.7% vs. 61.2%, P=0.372). While relapse rate was lower in older patients (15.5% vs. 22.6%, P=0.093), NRM was higher in older patients (29.7% vs. 18.8%,P=0.094). Conclusion: AYA pts. occupy a unique niche amongst AML as a whole. While treatment responses have improved in general, there may be potential for further gains in these patients. Increased tolerance for more intense treatment strategies as well as the incorporation of novel agents into standard treatment protocols may provide a means to optimize care in AYA patients. Finally, research is needed to elucidate biological mechanisms and predictors of disease behavior instead of arbitrary, age-stratified treatment schema. Disclosures McNamara: Novartis Pharmaceutical Canada Inc.: Consultancy. Schimmer:Jazz Pharmaceuticals: Consultancy; Medivir Pharmaceuticals: Research Funding; Novartis Pharmaceuticals: Consultancy; Otsuka Pharmaceuticals: Consultancy. Schuh:Astellas: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Teva Canada Innovation: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Agios: Honoraria; Jazz: Honoraria, Membership on an entity's Board of Directors or advisory committees. Maze:Pfizer Inc: Consultancy; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Yee:Astellas: Membership on an entity's Board of Directors or advisory committees; Millennium: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; Astex: Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; MedImmune: Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Hoffman La Roche: Research Funding. Minden:Trillium Therapetuics: Other: licensing agreement. Gupta:Incyte: Honoraria, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sierra Oncology: Honoraria, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Long Term Outcome of Lenalidomide-Dexamethasone (Rd) Vs Melphalan-Lenalidomide-Prednisone (MPR) Vs Cyclophosphamide-Prednisone-Lenalidomide (CPR) As Induction Followed By Lenalidomide-Prednisone (RP) Vs Lenalidomide (R) As Maintenance in a Community-Based Newly Diagnosed Myeloma Population: Updated Analysis of EMN01 Phase III Study

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 901-901
Author(s):  
Sara Bringhen ◽  
Massimo Offidani ◽  
Pellegrino Musto ◽  
Anna Marina Liberati ◽  
Giulia Benevolo ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Phase Iii ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Community Based ◽  
Advisory Committees ◽  
Risk Of Death ◽  
Grade 3 ◽  
To Receive

Abstract Introduction : Rd and MPR showed to be effective combinations in elderly newly diagnosed multiple myeloma (NDMM) patients (pts). Cyclophosphamide is a less toxic alkylating alternative agent. EMN01 is the first trial to formally compare these three different Lenalidomide-based combinations. Maintenance with Lenalidomide has been recently approved in patients eligible for autologous stem cell transplant (ASCT). Few data are available about the best combination as maintenance in patients not eligible for ASCT. Methods : 662 pts with NDMM were randomized to receive 9 28-day cycles of Rd (lenalidomide 25 mg/day for 21 days; dexamethasone 40 mg on days 1,8,15 and 22 in pts 65-75 years old and 20 mg in those &gt;75 years), MPR (lenalidomide 10 mg/day for 21 days; melphalan orally 0.18 mg/Kg for 4 days in pts 65-75 years old and 0.13 mg/Kg in &gt;75 years pts; prednisone 1.5 mg/Kg for 4 days) or CPR (lenalidomide 25 mg/day for 21 days; cyclophosphamide orally 50 mg/day for 21 days in pts 65-75 years old and 50 mg every other day in &gt;75 years pts; prednisone 25 mg every other day). After induction, pts were randomized to receive maintenance with lenalidomide alone (R; 10 mg/day for 21 days) or with prednisone (RP; R, 10 mg/day for 21 days and P, 25 mg every other day), until disease progression. Results : Pts characteristics were well balanced in all groups; 217 pts in Rd, 217 in MPR and 220 in CPR arms could be evaluated. After a median follow-up of 63.7 months, median PFS was 23.2 months in MPR, 18.9 months in CPR and 18.6 months in Rd (MPR vs CPR p=0.02; MPR vs Rd p=0.08). Median overall survival (OS) was 79.9 months in MPR, 69.4 months in CPR and 68.1 months in Rd (MPR vs CPR p=0.98; MPR vs Rd p=0.64). The most common grade ≥3 adverse event (AEs) was neutropenia: 64% in MPR, 29% in CPR and 25% in Rd pts (p&lt;0.0001). Grade ≥3 non hematologic AEs were similar among arms. At the end of induction, 402 pts were eligible for maintenance, 198 in the RP and 204 in the R groups. PFS from start of maintenance was 22.2 months in the RP group and 17.6 in the R group, with 20% reduced the risk of death/progression for pts receiving RP maintenance (HR 0.81, p=0.07; Figure 1). A subgroup analysis was performed to determine the consistency of RP vs R treatment effect in different subgroups using interaction terms between treatment and cytogenetic abnormalities, ISS, age, sex, induction treatment and response before maintenance (Figure 1). No difference in OS was observed (HR 1.02, p=0.93) but the OS analysis was limited by the low number of events. Median duration of maintenance was 23.0 months in RP pts and 20.5 months in R pts, 14% and 13% of pts discontinued due to AEs, in RP and R groups, respectively. Conclusion : This phase III trial compared 2 different Lenalidomide-containing induction regimens and 2 different Lenalidomide-containing maintenance regimens in an elderly community-based NDMM population. MPR prolonged PFS by approximately 5 months, yet the higher incidence of hematologic toxicity should be carefully considered. The addition of low-dose prednisone to standard lenalidomide maintenance reduced the risk of death/progression by 20%, with a good safety profile. Updated results will be presented at the meeting. Disclosures Bringhen: Mundipharma: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Celgene: Honoraria; Bristol Myers Squibb: Honoraria; Karyipharm: Membership on an entity's Board of Directors or advisory committees. Offidani: celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Musto: Celgene: Honoraria; Janssen: Honoraria. Gaidano: Gilead: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Roche: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. De Sabbata: Celgene: Membership on an entity's Board of Directors or advisory committees. Palumbo: Sanofi: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Binding Site: Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Merck: Consultancy, Honoraria, Research Funding; Genmab A/S: Consultancy, Honoraria, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Consultancy, Employment, Equity Ownership, Honoraria, Research Funding. Hájek: Amgen, Takeda, BMS, Celgene, Novartis, Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Honoraria; Pharma MAR: Consultancy, Honoraria. Boccadoro: Novartis: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; AbbVie: Honoraria; Mundipharma: Research Funding; Sanofi: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding.

scholarly journals Efficacy and Safety of Ravulizumab in Older Patients Aged >65 Years with Paroxysmal Nocturnal Hemoglobinuria in the 301 and 302 Phase 3 Extension Studies

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 42-43
Author(s):  
Regis Peffault De Latour ◽  
Jeffrey Szer ◽  
Austin Kulasekararaj ◽  
Jin Seok Kim ◽  
Caroline I. Piatek ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Older Patients ◽  
Research Funding ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Complement Inhibitor ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Advisory Committees ◽  
Treatment Naïve ◽  
Secondary Endpoints

Background: In the two largest phase 3 studies in patients with paroxysmal nocturnal hemoglobinuria (PNH), ravulizumab given every 8 weeks was noninferior to eculizumab given every 2 weeks across all efficacy endpoints. Data on efficacy and safety of ravulizumab in patients aged &gt;65 years with PNH are limited. Aims: To compare the efficacy and safety of ravulizumab in patients with PNH aged &gt;65 years with those aged ≤65 years. Methods: The population included patients from two phase 3 studies that assessed ravulizumab vs eculizumab in complement-inhibitor-naïve (301; NCT02946463) and -experienced (302; NCT03056040) adults with PNH. In study 301, patients were aged ≥18 years with a confirmed PNH diagnosis by flow cytometry and had a lactate dehydrogenase (LDH) level ≥1.5x upper limit of normal (ULN; 246U/L). In study 302, patients were aged ≥18 years with a confirmed PNH diagnosis by flow cytometry, were clinically stable on eculizumab having received ≥6 months of treatment and had a LDH level ≤1.5x ULN. Patients were randomized to either ravulizumab or eculizumab for 26 weeks after which all received ravulizumab up to 52 weeks. This prespecified analysis stratified patients by age: ≤65 or &gt;65 years. Primary endpoints included percentage change in LDH from baseline to weeks 26 and 52, percentage of patients achieving LDH-normalization (LDH-N; LDH levels: ≤1x ULN) at weeks 26 and 52 and transfusion avoidance (TA) from baseline to weeks 26 and 52. Breakthrough hemolysis (BTH), hemoglobin (Hgb) stabilization and FACIT-fatigue score were secondary endpoints. Treatment emergent adverse events (TEAEs) were assessed as an indicator of safety. Results: A total of 58 patients aged &gt;65 years and 383 patients aged ≤65 years were included. Disposition and medical history were similar among subgroups at baseline (Table 1). Results for primary and secondary endpoints for the two subgroups were comparable across studies and efficacy was maintained through 52 weeks. A higher proportion of treatment-experienced patients (&gt;65 years) achieved all endpoints vs -naïve patients (Table 2). The percentage change in LDH levels from baseline to 26 and 52 weeks was similar between subgroups in study 301 (-66.5 to -80.0%) whereas in study 302, LDH levels remained stable in all subgroups up to 52 weeks (-3.7 to 22%). The percentage of patients achieving LDH-N in both studies at 26 and 52 weeks differed; 43.8-63.9% of patients aged ≤65 years achieved LDH-N compared with 21.4-77.8% of patients aged &gt;65 years. A higher proportion of older treatment-experienced patients (57.1‒77.8%) achieved LDH-N compared with older treatment-naive patients (21.4‒50.0%) at 26 and 52 weeks. In patients aged ≤65 years in both studies, 63.7‒89.4% achieved TA. In the &gt;65 years subgroup, 14.3‒50.0% of treatment-naive patients achieved TA whereas in study 302, 54.5‒72.7% of patients achieved TA. The number of BTH events was low, with no events reported in older patients to date. Hgb stabilization was consistent in the ≤65 year subgroup between the studies; a higher proportion of older patients in study 302 (45.5‒71.4%) achieved stabilized Hgb compared with older patients in study 301 (14.3‒35.3%). A clinically significant 3-point change was seen in FACIT-fatigue scores (indicating improvements in fatigue), with higher scores observed for ravulizumab in both subgroups (Figure 1). One patient discontinued the extension of study 301 due to lung cancer onset during the 26-week period and died following discontinuation. Headache was the most frequent TEAE. The incidence of TEAEs reported during ravulizumab treatment up to 52 weeks did not increase vs the 26-week period, with few events (Table 3) and no difference between subgroups. Conclusions: We present clinical outcomes in the largest cohort of patients with PNH (&gt;65 years) on ravulizumab in a clinical trial setting to date. Ravulizumab was associated with similar efficacy and safety in both age subgroups and showed consistent and durable efficacy through 52 weeks of treatment. A higher proportion of patients in study 302 achieved all efficacy endpoints than in study 301, which can be due to patients' prior complement inhibitor experience. This observation was more evident in older patients. There were no BTH events in the older patients to date, and the number of infections in both subgroups was low. Ravulizumab was well tolerated in older patients with no additional safety concerns compared to younger patients. Disclosures Peffault De Latour: Apellis: Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Alexion Pharmaceuticals Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Szer:Pfizer: Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Apellis: Consultancy; Alexion Pharmaceuticals Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Prevail Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Speakers Bureau. Kulasekararaj:Alexion Pharmaceuticals Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kim:Alexion Pharmaceuticals Inc.: Honoraria, Research Funding. Piatek:Alexion Pharmaceuticals: Consultancy, Research Funding. Kulagin:Alexion Pharmaceuticals Inc.: Consultancy, Research Funding. Hill:Alexion Pharmaceuticals Inc.: Current Employment. Wang:Alexion Pharmaceuticals Inc.: Current Employment. Yu:Alexion Pharmaceuticals Inc.: Current Employment. Ogawa:Alexion Pharmaceuticals Inc.: Current Employment. Schrezenmeier:Alexion Pharmaceuticals Inc.: Honoraria, Research Funding. Lee:Alexion Pharmaceuticals Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

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