scholarly journals Estimation of Long-Term Survival with Tafasitamab + Lenalidomide in Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 9-10
Author(s):  
Gilles Salles ◽  
Budhaditya Goswami ◽  
Vincenzo Bagnardi ◽  
Debarshi Dey ◽  
Mark Winderlich ◽  
...  
Keyword(s):  
Weibull Distribution ◽  
Survival Benefit ◽  
Survival Rates ◽  
B Cell Lymphoma ◽  
Parametric Models ◽  
Cure Model ◽  
Mixture Cure Model ◽  
Advisory Role

Background L-MIND (NCT02399085) is an ongoing, open-label, single-arm, Phase II study of tafasitamab + lenalidomide (LEN) in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who are ineligible for autologous stem cell transplant. Progression-free survival (PFS) estimates the treatment effect of the study drug only, while overall survival (OS) also includes effects of potential subsequent cancer treatments or palliative care. Given that not all OS and PFS events have occurred after a long follow-up duration, traditional survival analyses may underestimate survival benefit for tafasitamab + LEN by assuming the same mortality rate for the whole population. We used mixture cure models to estimate the proportion of long-term survivors (LTS) and survival benefit associated with tafasitamab + LEN treatment. Methods In the L-MIND study (data cut-off: Nov 30, 2019), 80/81 enrolled patients with R/R DLBCL received tafasitamab + LEN, with a median and maximum follow-up duration of 31.8 months (95% CI: 27.2-35.9) and 43.5 months, respectively. The Kaplan-Meier (KM) plots of PFS and OS were observed to plateau after 30 months, with the majority of events reported up to that time-point and very few events beyond this time-point. Patients without a PFS event or patients who did not decease after the observed plateau exhibit a high survival benefit from tafasitamab + LEN treatment and are considered LTS. Thus, the patient population can be considered to consist of two sub-populations - LTS and non-LTS. A "mixture cure model" was fitted on the PFS and OS data to estimate the proportion of LTS and associated mean survival for the two sub-populations (Lambert PC, et al. 2007). To incorporate background mortality (Bansal, et al. 2019), age- and sex-specific US mortality rates (US CDC 2017) were factored in for the entire study population (enrolled in Europe and US). The weighted average of the mean survival for the two sub-populations provided an estimate of the mean survival for the whole population. For comparative purposes, standard parametric models without considering an LTS proportion were fitted on PFS and OS data additionally. Sensitivity analyses were performed considering different survival distributions (exponential distribution, Weibull distribution and log-logistic distribution). Results By using a mixture cure model fitted to PFS and OS data separately, the estimated proportion of LTS for the tafasitamab + LEN combination was 42% (95% CI: 30-55) and 47% (95% CI: 29-66), respectively. The predicted mean survival when mixture cure model was fitted on PFS data was 16.7 years for LTS patients vs 0.5 years for non-LTS patients, yielding 7.3 years for the overall population. Under this mixture cure model, the survival rates of patients with tafasitamab + LEN treatment were 40.2% and 36.0% at 2 and 5 years. Similar results were obtained when the mixture cure model was fitted on OS data. Using a standard parametric model (Weibull distribution), the predicted mean survival in the overall population was 2.8 years fitting PFS data (Figure 1) and 4.5 years fitting OS data (Figure 2). Conclusions PFS and OS KM curves for the L-MIND study reaching a long plateau and not following a Weibull distribution suggest the presence of an LTS subgroup. Standard parametric models may lead to a biased estimation of the OS benefit in such situations. The mixture cure model suggests that the treatment of R/R DLBCL patients with tafasitamab + LEN is associated with a high LTS proportion. The survival rates of patients with tafasitamab + LEN treatment were 40.2% and 36.0% at 2 and 5 years. Disclosures Salles: Takeda:Honoraria;BMS/Celgene:Honoraria, Other: consultancy or advisory role;Debiopharm:Consultancy, Honoraria, Other: consultancy or advisory role;Genmab:Honoraria, Other;Karyopharm:Honoraria;Kite, a Gilead Company:Honoraria, Other: consultancy or advisory role ;Epizyme:Honoraria, Other: consultancy or advisory role;Janssen:Honoraria, Other: consultancy or advisory role;Abbvie:Other: consultancy or advisory role;Roche:Honoraria, Other: consultancy or advisory role;Novartis:Honoraria, Other: consultancy or advisory role;MorphoSys:Honoraria, Other: consultancy or advisory role;Autolos:Other: consultancy or advisory role.Goswami:MorphoSys AG:Ended employment in the past 24 months.Bagnardi:MorphoSys AG:Consultancy.Dey:MorphoSys AG:Current Employment.Winderlich:MorphoSys AG:Current Employment.Ambarkhane:MorphoSys AG:Current Employment.Huang:MorphoSys AG:Current Employment.Nowakowski:Curis:Consultancy;Kymera:Consultancy;Kite:Consultancy;Ryvu:Consultancy, Membership on an entity's Board of Directors or advisory committees;Celgene/BMS:Consultancy, Research Funding;Seattle Genetics:Consultancy;MorphoSys:Consultancy, Research Funding;NanoString:Research Funding.

Effect of ipilimumab treatment on 18-month survival: Update of patients (pts) with advanced melanoma treated with 10 mg/kg ipilimumab in three phase II clinical trials

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9033-9033
Author(s):  
S. O'Day ◽  
J. Weber ◽  
C. Lebbe ◽  
M. Maio ◽  
H. Pehamberger ◽  
...  
Keyword(s):  
Phase Ii ◽  
Survival Data ◽  
Survival Benefit ◽  
Survival Rates ◽  
Advanced Melanoma ◽  
Controlled Study ◽  
Term Survival ◽  
Long Term Survival

9033 Background: The monoclonal antibody ipilimumab targets cytotoxic T lymphocyte antigen-4. Updated survival data (≤32.5 months follow-up) from 3 Phase II trials of ipilimumab in pts with mostly pretreated advanced melanoma are reported. Methods: Study CA184008 was an open-label, single-arm study of ipilimumab 10 mg/kg. Study CA184022 was a randomized, dose-ranging study of ipilimumab 0.3, 3, or 10 mg/kg. Study CA184007 was a randomized, placebo-controlled study of the effect of budesonide on gastrointestinal immune-related adverse events in pts receiving ipilimumab 10 mg/kg. In all studies, ipilimumab was given every 3 weeks (Q3W) × 4 (induction); eligible pts could continue to receive maintenance ipilimumab Q12W from week 24. Pts continue to be followed-up to determine long-term survival. Results: With a median follow-up ranging from 10.1 to 16.3 months and reaching up to 32.5+ months, pts receiving 10 mg/kg ipilimumab showed durable survival; 12- and 18-month survival rates are presented [ Table ]. The tail of the Kaplan-Meier curve flattened at 18 months, indicating that a substantial proportion of patients continued to survive beyond the updated follow-up period in all three studies. Long-term survivors include pts with disease progression (PD) per modified World Health Organization (mWHO) criteria. Conclusions: Ipilimumab may result in a long-term survival benefit in pts with advanced melanoma, where 18-month survival rates across 3 Phase II studies range from 34.5% to 39.4% for previously treated pts. These results indicate that more than 1/3 of ipilimumab-treated pts with advanced melanoma experience a long-term survival benefit, including some pts characterized as PD by mWHO. The survival data continue to mature, and follow-up is ongoing. [Table: see text] [Table: see text]

scholarly journals Surgical treatment of pulmonary artery sarcoma: a report of 17 cases

2021 ◽  
Vol 11 (1) ◽  
pp. 204589402098639
Author(s):  
Wu Song ◽  
Long Deng ◽  
Jiade Zhu ◽  
Shanshan Zheng ◽  
Haiping Wang ◽  
...  
Keyword(s):  
Pulmonary Artery ◽  
Survival Rates ◽  
Tumor Resection ◽  
Long Term Results ◽  
Pulmonary Endarterectomy ◽  
Pulmonary Artery Sarcoma ◽  
The Mean ◽  
Operative Findings

Pulmonary artery sarcoma (PAS) is a rare and devastating disease. The diagnosis is often delayed, and optimal treatment remains unclear. The aim of this study is to report our experience in the surgical management of this disease. Between 2000 and 2018, 17 patients underwent operations for PAS at our center. The medical records were retrospectively reviewed to evaluate the clinical characteristics, operative findings, the postoperative outcomes, and the long-term results. The mean age at operation was 46.0 ± 12.4 years (range, 26–79 years), and eight (47.1%) patients were male. Six patients underwent tumor resection alone, whereas the other 11 patients received pulmonary endarterectomy (PEA). There were two perioperative deaths. Follow-up was completed for all patients with a mean duration of 23.5 ± 17.6 months (1–52 months). For all 17 patients, the median postoperative survival was 36 months, and estimated cumulative survival rates at 1, 2, 3, and 4 years were 60.0%, 51.4%, 42.9%, and 21.4%, respectively. The mean survival was 37.0 months after PEA and 14.6 months after tumor resection only ( p = 0.046). Patients who had no pulmonary hypertension (PH) postoperatively were associated with improved median survival (48 vs. 5 months, p = 0.023). In conclusion, PAS is often mistaken for chronic pulmonary thromboembolism. The prognosis of this very infrequent disease remains poor. Early detection is essential for prompt and best surgical approach, superior to tumor resection alone, and PEA surgery with PH relieved can provide better chance of survival.

Survival trends in chronic lymphocytic leukemia in the era of oral targeted therapies in the United States: SEER database analyses (1985 to 2017).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7524-7524
Author(s):  
Neda Alrawashdh ◽  
Ali McBride ◽  
Daniel O. Persky ◽  
Joann Sweasy ◽  
Brian Erstad ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Survival Rates ◽  
Relative Survival ◽  
Lymphocytic Leukemia ◽  
Disease Stage ◽  
Seer Database ◽  
Cure Model ◽  
Gender And Age ◽  
Long Term Survivors

7524 Background: The survival of chronic lymphocytic leukemia (CLL) patients has progressively improved after the approval of new targeted therapy for first-line treatment and relapsed disease. We performed a corresponding analysis from the U.S. population-based SEER database (1973–2017) to explore the trend of survival and the effect of advanced CLL treatment on overall survival in CLL patients. Methods: Data were extracted from SEER*Stat for all patients 15 years or older with a primary diagnosis of CLL with or without subsequent cancers. A period analysis was performed to estimate the 5- and 10-year relative survival rates for patients diagnosed (dx) during different calendar periods from 1985 to 2017, based on gender and age at time of diagnosis (15–44, 45–54, 55–64, 65–74, 75–84, 85 years or older). A mixture cure model was used to examine the proportion of long-term survivors per gender and age category among CLL patients diagnosed between 1985 and 2015. Cox proportional hazard modeling was used to calculate the hazard ratios (HRs) of death adjusted for gender and age at diagnosis for two cohorts: (a) diagnosed in 2000–2003 and followed to 2012; (b) 2004–2007 and followed to 2015. Results: For males, the 5-year age-adjusted relative survival rate improved progressively from 72.0% (dx 1985-1989) to 88.2% (dx 2010-2014); for females, from 76.8% (dx 1985-1989) to 90.8% (dx 2010-2014). The corresponding 10-year age-adjusted relative survival rates were 47.3% (dx 1985-1989) and 72.5% (dx 2005-2009) for males; and 58.2% (dx 1985-1989) and 78.7% (dx 2005-2009) for females. The table below shows the proportions of long-term survivors for the 1985–2017 cohort as estimated in the mixed cure model. The HRs (95%CI) of death for cohort (b) in comparison to cohort (a) were 0.58 (0.43–0.78), 0.58 (0.48–0.70), 0.57 (0.49–0.67), 0.68 (0.54–0.85); and 0.83 (0.68–1.02) for age categories of 45–54, 55–64, 65–74, 75–84, and 85 years or old. Conclusions: Survival is significantly improved by calendar period among patients diagnosed after 2004 and treated in the era of advanced therapies. Females and younger patients had a higher probability of long term survival. Future studies should consider such covariates as treatment type, disease stage and genetics.[Table: see text]

Abstract 2130: Long-term Outcomes of Adult Atrial Septal Defect With Severe Pulmonary Hypertension After Surgical Closure

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Jeong-Hoon Kim ◽  
Duk-Hyun Kang ◽  
Jong-Young Lee ◽  
Jong-Min Song ◽  
Tae-Jin Yun ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Elderly Patients ◽  
Atrial Septal Defect ◽  
Septal Defect ◽  
Survival Rates ◽  
Severe Pulmonary Hypertension ◽  
Term Survival ◽  
Surgical Closure

The benefits of surgical closure has been unclear in adult atrial septal defect (ASD) with severe pulmonary hypertension (PHT), and we tried to evaluate improvement of PHT and long-term survival after surgical closure compared to medical follow-up. Methods: From 1996 to 2006, we included a total of 71 adult ASD patients (age; 43±15 years) with severe PHT documented by echocardiography. The inclusion criteria were defined as ASD diameter > 15 mm, enlarged right ventricle, and the baseline peak velocity of tricuspid regurgitation (TR) ≥ 4.0 m/sec. We excluded 5 patients with Eisenmenger syndrome documented by cardiac catheterization. Surgical closure was performed on 55 patients (OP group) and the remaining 16 patients were followed up medically (MED group). The improvement of PHT was defined as TR velocity ≤ 3.5 m/sec on follow-up echo. Results: Baseline characteristics and clinical results were compared between the two groups in table . There were no significant differences in terms of gender, ASD diameter, cardiac rhythm, and TR velocity, but the MED group was significantly older. During follow-up of 46±33 months, there were 5 deaths in the MED group and no operative or late death in the OP group, and the 5-year actuarial survival rate of the OP group was significantly higher than the MED group (58±15%, p<0.05). On subgroup analysis according to age, the OP group showed significantly better survival rates than the MED group (p<0.05) in elderly patients (age > 50). In the OP group, TR velocity was significantly decreased from 4.5±0.4 to 3.0±0.7 m/sec on follow-up echo, and improvement of PHT was observed in 47 (85%) patients. On multivariate analysis, female gender and lower baseline TR velocity were the significant independent predictors of improved PHT after surgery. Conclusions: In adult ASD with severe PHT, surgical closure can be safely performed and improve PHT effectively. Especially in elderly patients, ASD closure is significantly related with the better survival rates.

scholarly journals Long-Term Follow-Up of Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy

2020 ◽  
Vol 38 (32) ◽  
pp. 3805-3815
Author(s):  
Kathryn M. Cappell ◽  
Richard M. Sherry ◽  
James C. Yang ◽  
Stephanie L. Goff ◽  
Danielle A. Vanasse ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T

PURPOSE Anti-CD19 chimeric antigen receptors (CARs) are artificial fusion proteins that cause CD19-specific T-cell activation. Durability of remissions and incidence of long-term adverse events are critical factors determining the utility of anti-CD19 CAR T-cell therapy, but long-term follow-up of patients treated with anti-CD19 CAR T cells is limited. This work provides the longest follow-up of patients in remission after anti-CD19 CAR T-cell therapy. METHODS Between 2009 and 2015, we administered 46 CAR T-cell treatments to 43 patients (ClinicalTrials.gov identifier: NCT00924326 ). Patients had relapsed B-cell malignancies of the following types: diffuse large B-cell lymphoma or primary mediastinal B-cell lymphoma (DLBCL/PMBCL; n = 28), low-grade B-cell lymphoma (n = 8), or chronic lymphocytic leukemia (CLL; n = 7). This report focuses on long-term outcomes of these patients. The CAR used was FMC63-28Z; axicabtagene ciloleucel uses the same CAR. Cyclophosphamide plus fludarabine conditioning chemotherapy was administered before CAR T cells. RESULTS The percentages of CAR T-cell treatments resulting in a > 3-year duration of response (DOR) were 51% (95% CI, 35% to 67%) for all evaluable treatments, 48% (95% CI, 28% to 69%) for DLBCL/PMBCL, 63% (95% CI, 25% to 92%) for low-grade lymphoma, and 50% (95% CI, 16% to 84%) for CLL. The median event-free survival of all 45 evaluable treatments was 55 months. Long-term adverse effects were rare, except for B-cell depletion and hypogammaglobulinemia. Median peak blood CAR-positive cell levels were higher among patients with a DOR of > 3 years (98/µL; range, 9-1,217/µL) than among patients with a DOR of < 3 years (18/µL; range, 0-308/μL, P = .0051). CONCLUSION Complete remissions of a variety of B-cell malignancies lasting ≥ 3 years occurred after 51% of evaluable anti-CD19 CAR T-cell treatments. Remissions of up to 9 years are ongoing. Late adverse events were rare.

Age at symptom onset and long-term survival in patients with neurofibromatosis Type 2

2003 ◽  
Vol 99 (3) ◽  
pp. 480-483 ◽  
Author(s):  
Goro Otsuka ◽  
Kiyoshi Saito ◽  
Tetsuya Nagatani ◽  
Jun Yoshida
Keyword(s):  
Symptom Onset ◽  
Survival Rates ◽  
Neurofibromatosis Type ◽  
Neurofibromatosis Type 2 ◽  
Vestibular Schwannomas ◽  
Content Type ◽  
Fine Print

Object. Neurofibromatosis Type 2 (NF2) is an intractable disorder predisposing to multiple, recurrent tumors of the central nervous system (CNS). To clarify the survival rate and characteristics that predict poor survival, we retrospectively reviewed clinical data in cases of NF2. Methods. From among 283 patients with neurofibromatosis who had been registered in a nationwide study in Japan between 1986 and 1987, 74 patients with bilateral vestibular schwannomas were analyzed. The mean duration of follow up after diagnosis was 121 months (range 2–287 months). Results of a Kaplan—Meier product-limit analysis indicated that overall 5-, 10-, and 20-year patient survival rates following diagnosis of NF2 were 85, 67, and 38%, respectively. Early onset of the initial symptom significantly compromised survival; 5-, 10-, and 20-year survival rates in patients with symptom onset at an age younger than 25 years were 80, 60, and 28%, respectively, whereas in patients with symptom onset at an age of 25 years or older the rates were 100, 87, and 62%, respectively. Patients with small vestibular schwannomas at diagnosis (< 2 cm in diameter) had better rates of survival. Other variables such as sex, additional tumors in the CNS, or dermal abnormalities did not significantly affect survival. Conclusions. This first report of long-term follow-up results concerning the survival of patients with NF2 indicates an adverse effect of early symptom onset.

scholarly journals Inter-relationships between Gender, Frailty and 10-Year Survival in Older Italian Adults: an observational longitudinal study

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Graziamaria Corbi ◽  
Francesco Cacciatore ◽  
Klara Komici ◽  
Giuseppe Rengo ◽  
Dino Franco Vitale ◽  
...  
Keyword(s):  
Longitudinal Study ◽  
Cox Model ◽  
Survival Rates ◽  
Staging System ◽  
Female Gender ◽  
Term Survival ◽  
Fractional Polynomial ◽  
The Impact

AbstractAim of the present study was to assess the impact of gender on the relationship between long-term mortality and clinical frailty. In an observational, longitudinal study on 10-year mortality, we examined 1284 subjects. The Frailty Staging System was used to assess frailty. The Cox model was employed to assess variables independently associated with survival using a backward stepwise algorithm. To investigate the possible interactions between gender and the selected variables, an extension of the multivariable fractional polynomial algorithm was adopted. Women were more likely to be older, have a higher disability, present with more comorbidities, consume more drugs, be frail and have a higher rate of survival at the follow-up than were men. At the Cox multivariate analysis only age (HR 2.26), female gender (HR 0.43), and number of drugs (HR 1.57) were significant and independent factors associated with all-cause mortality. In the survival analyses, only frailty (vs no frailty) showed significant interaction with gender (p < 0.001, HR = 1.92). While the presence of frailty reduced the survival rate in women, no effect was observed in men. Importantly, frail women showed higher survival rates than did both frail and no frail men. The main finding of the present study is that gender shapes up the association between frailty and long-term survival rates.

scholarly journals The Prognosis and Oncological Predictor of Urachal Carcinoma of the Bladder: A Large Scale Multicenter Cohort Study Analyzed 203 Patients With Long Term Follow-Up

2021 ◽  
Vol 11 ◽  
Author(s):  
Young Dong Yu ◽  
Young Hwii Ko ◽  
Jong Wook Kim ◽  
Seung Il Jung ◽  
Seok Ho Kang ◽  
...  
Keyword(s):  
Large Scale ◽  
Survival Rates ◽  
Stage Iii ◽  
Pathological Stage ◽  
Urachal Carcinoma ◽  
Multicenter Cohort ◽  
Long Term Follow Up ◽  
The Mean

AimThis study evaluated the prognosis and survival predictors for bladder urachal carcinoma (UC), based on large scale multicenter cohort with long term follow-up database.MethodsA total 203 patients with bladder UC treated at 19 hospitals were enrolled. Clinical parameters on carcinoma presentation, diagnosis, and therapeutic methods were reviewed for the primary cancer and for all subsequent recurrences. The stage of UC was stratified by Mayo and Sheldon pathological staging system. Oncological outcomes and the possible clinicopathological parameters associated with survival outcomes were investigated.ResultsThe mean age of the patients was 54.2 years. Among the total of 203 patients, stages I, II, III, and IV (Mayo stage) were 48 (23.8%), 108 (53.5%), 23 (11.4%), and 23 (11.4%), respectively. Gross hematuria and bladder irritation symptoms were the two most common initial symptoms. The mean follow-up period was 65 months, and 5-year overall survival rates (OS), cancer-specific survival rates (CSS), and recurrence-free survival rates (RFS) were 88.3, 83.1, and 63.9%, respectively. For the patients with Mayo stage ≥III, OS, CSS, and RFS were significantly decreased to 38.0, 35.2, and 28.4%, respectively. The higher pathological stage (Mayo stage ≥III, Sheldon stage ≥IIIc), positive surgical margin (PSM), and positive lymphovascular invasion (PLM) were independent predictors of shorter OS, CSS, and RFS.ConclusionThe pathological stage, PSM, and PLM were significantly associated with the survival of UC patients, emphasizing an importance of the complete surgical resection of tumor lesion.

scholarly journals OT-Equator® Attachments Comparison for Retaining an Early Loaded Implant Overdenture on Two or Three Implants: 1 Year RCT Preliminary Data

2021 ◽  
Vol 11 (18) ◽  
pp. 8601
Author(s):  
Marco Tallarico ◽  
Gabriele Cervino ◽  
Marco Montanari ◽  
Roberto Scrascia ◽  
Emiliano Ferrari ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Survival Rates ◽  
Marginal Bone Loss ◽  
Patient Centered ◽  
Randomized Controlled ◽  
Multicenter Randomized Controlled Trial ◽  
Long Term Follow Up ◽  
Implant Overdenture

The purpose of this multicenter randomized controlled trial was to compare the clinical, radiographic, and patient-centered outcomes of early loaded mandibular overdentures deliberately placed on two or three implants. The outcomes were: implant and prosthesis success and survival rates; biological and technical complications; marginal bone loss; patient satisfaction; and periodontal parameters. The results showed no differences between the groups in any of the outcomes analyzed. With the limitations of the present study, and looking at long-term follow-up, the gold standard of prosthetic rehabilitations with attachments, in agreement with the scientific community, should prefer two non-splinted implants.

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