Patterns of Care of Diffuse Large B Cell Lymphoma Patients 80 Years and Older: Worse Outcomes after Treatment without Increased Relapse

Abstract Introduction: Very advanced age (≥80 years) DLBCL patients have worse prognosis. These unfavorable outcomes are largely considered to be a result of the combined effects of increased comorbidities, frailty, diminished tolerance and access to effective chemoimmunotherapy. It is not clear yet whether DLBCL patients of very advanced age have disease that is intrinsically more aggressive. Methods: We accessed the Stem Cell Transplant and Hematologic Malignancies database of University Hospitals Seidman Cancer Center for DLBCL patients diagnosed between 2000 and 2016. Information collected included demographic characteristics, baseline laboratory and disease information, as well as treatment details. Progression free survival and overall survival were calculated from time of diagnosis using Kaplan Meier methodology, comparisons were done with log rank. Cumulative incidence of relapse with death as competing risk was calculated for patients who underwent treatment, comparisons between age groups were done with the Gray test. Results: A total of 542 DLBCL patients were identified, 85 (16%) were older than 80 years. Table 1 shows the baseline demographic and disease characteristics. Older patients had a higher incidence of comorbidities, specifically cardiovascular comorbidities, prior renal insufficiency, and hyperlipidemia. Expectedly, very elderly patients had higher R-IPI, with a trend towards worse performance status that did not reach statistical difference. The proportion of patients diagnosed with non - germinal center DLBCL was not different than younger DLBCL patients, and there was no statistical difference in the incidence of double expressor or double hit lymphomas, possibly secondary to the small number of patients tested. A smaller proportion of patients ≥ 80 years received antineoplastic therapy (89% vs. 98%, p = 0.001), and use of less intense therapy was more common (table 2). Sixty one percent of patients, however, were still treated with R-CHOP (38.8%) or R-miniCHOP (22.2%). The overall response rate (ORR) for any therapy was 68.2%, lower than the ORR for younger patients (85.9%, p = 0.007). When only patients treated with RCHOP/R-miniCHOP were included, the difference in ORR was smaller, though still statistically significant (77.5% vs. 89.8%, p = 0.021). Median number of cycles was similar (5 vs. 6 cycles, respectively). Patients of all ages treated with single agent rituximab presented an ORR of 43%. After a median of 40 months follow up, estimated 4-year overall survival was 42% (95% CI 31-54%) for patients ≥ 80 years, 67% for patients aged between 60 and 79 years (95% CI 61-74%) and 78% for patients < 60 years (95% CI 73-84%) (Figure 1). Four - year survival for patients ≥80 years treated with R-CHOP or R-miniCHOP chemoimmunotherapy was 50% (95% CI 36-65%) vs. 75% for younger patients (95% CI 70-79%) (p<0.001), with 4-year PFS of 48% vs. 63% (95% CI 58-68%) (p = 0.04). Cumulative incidence of relapse (with death in remission as competing risk) for chemoimmunotherapy - treated patients at 1 and 4 years was 10% (95% CI 4-22%) and 20% (95% CI 11-37%), respectively for patients older than 80 years and 20% (95% CI 11-36%) and 29% (95% CI 25-35%), respectively for younger patients (p = 0.12) (Figure 2). There was no observed difference in the rates of disease - related mortality (53% vs. 61%, p = 0.5). Conclusions: Very elderly (≥80 years of age) DLBCL patients have significantly worse overall survival, progression free survival, and treatment response rates than younger patients. However, when chemoimmunotherapy is feasible, disease relapse rates are comparable to those of younger patients, and increased mortality does not appear to be a result of increased disease relapse. Additional research is needed to establish more widely applicable, better tolerated effective treatment regimens for this patient population. Disclosures Lazarus: Pluristem Ltd.: Consultancy. Malek:Takeda: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Sanofi: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau. Tomlinson:Foundation Medicine: Consultancy. Caimi:Genentech: Other: Advisory Board PArticipation, Research Funding; Kite Pharma: Other: Advisory Board Participation; Celgene: Speakers Bureau; Kite Pharma: Other: Advisory Board Participation.

Download Full-text

Treatment of Diffuse Large Cell Lymphoma (DLBCL) Patients Older Than 75 Years: Higher Mortality and Risk of Complications without Increased Risk of Relapse after Treatment

Blood ◽

10.1182/blood.v128.22.1863.1863 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1863-1863

Author(s):

Akiva Diamond ◽

Sabarish Ram Ayyappan ◽

Raisa Pinto ◽

Ehsan Malek ◽

Ben K. Tomlinson ◽

...

Keyword(s):

Overall Survival ◽

Cumulative Incidence ◽

Cardiovascular Events ◽

Older Patients ◽

Response Rates ◽

Competing Risk ◽

Relapse Free Survival ◽

Free Survival ◽

Younger Patients ◽

Disease Characteristics

Abstract Introduction: The prognostic relevance of age at diagnosis has long been recognized in DLBCL. Its role in the biology of disease has not been clarified, and it has been postulated that the worse prognosis of older DLBCL patients is a result of more aggressive disease combined with poor tolerance to aggressive therapy. The introduction of rituximab has improved the outcomes of DLBCL in all ages, whereas reduced dose and anthracycline-free regimens have improved access of elderly patients to more effective DLBCL therapy. Methods: We accessed the Hematologic Malignancies database of University Hospitals Seidman Cancer Center for DLBCL patients diagnosed between 2002 and 2014. Information collected included demographic as well as baseline laboratory and disease characteristics. Relapse and overall survival times were calculated from end of therapy and time of diagnosis, respectively, using the Kaplan Meier method, comparisons were done using the log-rank test. Cumulative incidence of major cardiovascular events (including myocardial infarction, coronary artery disease without infarction, congestive heart failure and arrhythmias) were calculated using death as competing risk; comparisons between groups were done using the Gray test. Results: A total of 400 DLBCL patients were identified, 95 were older than 75 years. Table 1 shows the baseline demographic and disease characteristics. Older patients had a higher incidence of comorbidities and higher rates of decreased performance status. There were no other differences in baseline disease characteristics. A smaller proportion of older patients proceeded to receive antineoplastic therapy (81% vs. 91%, p = 0.002). Therapy for older subjects was less intense (full dose R-CHOP 54.5% vs. 81.1%, p<0.001) with more planned and unplanned dose reductions (48% vs. 11%, p<0.001). Despite less intense therapy, response rates were not statistically different between the two age groups (84% vs. 87%, p = 0.687). After a median of 28 months follow up, estimated 3-year overall survival was 51% (95% CI 40-61.8%) for patients >75 years vs. 76% for younger patients (95% CI 70.6-80.9%)(p<0.001). In patients who received therapy (n=77 older than 75 years; n=281 for < 75 years), there was no difference in relapse-free survival from the start of treatment (3-year RFS: 77% (95% CI 66.5-88.5%) for patients > 75 years and 65% (95% CI 59.1-71.6%) for younger patients, p=0.155). The cumulative incidence (CI) of cardiovascular events, with death due to any other cause as a competing risk, was higher in subjects >75 years: 1-year CI was 15.3% vs. 7.6% in younger patients (p = 0.04). Conclusions: DLBCL patients older than 75 years have a higher mortality risk following DLBCL diagnosis than younger patients, despite having similar response rates and relapse free survival. While chemotherapy dose reduction does not appear to affect disease control, high rates of cardiovascular events suggest future studies should focus on the minimization of short and long term toxicities of therapy. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Outcome of Autologous Hematopoietic Cell Transplantation in First Complete Remission(CR1) in Patients with Peripheral T-Cell Lymphomas(PTCLs)

Blood ◽

10.1182/blood-2019-125666 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3315-3315

Author(s):

Shuo Liu ◽

Zhengming Jin ◽

Depei Wu ◽

Haiwen Huang

Keyword(s):

Overall Survival ◽

Stem Cell ◽

T Cell ◽

Cell Transplantation ◽

Cumulative Incidence ◽

Cell Lymphoma ◽

Statistical Significance ◽

Progression Free Survival ◽

T Cell Lymphoma ◽

Free Survival

Abstract Background Patients with peripheral T cell lymphomas (PTCLs) generally have a poor prognosis with conventional chemotherapy. Most studies demonstrates that, compared to the patients who did not achieve complete remission (CR) after initial therapy, the patients of PTCL who received autologous stem cell lymphoma (ASCT) as consolidation treatment show clearly advantage in survival. However, given the absence of randomized controlled studies, it is unproven that clinical value of consolidative ASCT for PTCL patients achieving CR1. There is a possibility that the survival is similar with or without up-front ASCT group. Thus, we collected the data of PTCL patients who attain CR1 following conventional chemotherapy in our center during the past 10 years. And the objective of this study is to evaluate overall survival(OS), progression-free survival(PFS), and cumulative incidence of relapse (CIR) between observation and first-line ASCT group. Patients and Methods Weconducted a retrospective study of patients with PTCL who were treated in our center from January 2009 to April 2019. The histopathologic diagnosis of all PTCL patients according to the World Health Organization classification. Exclusion criteria were the following: (1) anaplastic lymphoma kinase (ALK)-positive anaplastic large T-cell lymphoma; (2) cutaneous T cell lymphoma (CTCL); (3) concurrent B cell lymphomas; (4) natural killer/T-cell lymphoma (NK/TCL); (5) patients who underwent allogeneic stem cell transplantation. Furthermore, patients with PTCL age ≤65 years were included. Overall survival(OS )and progression-free survival(PFS) rates were estimated using the Kaplan-Meier method and Survival was compared using the log-rank test. Cumulative incidence of relapse (CIR) was compared by Gray's test competing risk test statistic. The level of statistical significance was set at p < 0.05. Results A total of 97 patients who met inclusion criteria were enrolled in our center from January 2009 to April 2019. And 59 (59/97, 60.8%)achieved CR1 after receiving induction chemotherapy. Table 1 summarizes the baseline characteristics for the patients in CR1. Of the 59 patients, 43 patients underwent observation and waiting in CR1, 16 patients underwent consolidative ASCT. PTCL NOS accounted for more than 50% at diagnosis in both groups. However, there was significant difference in median age between Non-ASCT group and ASCT group. Patients receiving ASCT were younger and in better physical condition. There were no difference in initial chemotherapy between two groups. Median follow-up time in the entire patient cohort for CR1 (59) was 31months. The median OS and PFS for patients who underwent observation in CR1 was 105 months and 20 months, the median OS and PFS for patients who underwent ASCT as consolidation treatment was 133 months and 91 months. There were no statistical significance in OS (105m vs. 133m, P=0.541) (Figure 1) and PFS (20m vs. 91m, P=0.237) (Figure 2). The estimated 2-year OS was 68.7% and 74.5% in the non-ASCT group and ASCT group, respectively. The estimated 2-year PFS was 41.9% and 62.5%, respectively. When considering incidence of disease relapse, the 2-year cumulative incidence of relapse in the non-ASCT and ASCT group was 41% and 25%, respectively. Again, however, this did not meet statistically significant(P=0.504) (Figure 3). Notably, among patients with advanced-stage disease, elevated LDH, extranodal involvement>1 sites or intermediate-to-high IPI scores, patients who received ASCT as consolidative treatment did not have long time survival compared to the non-ASCT group. Conclusion In conclusion, for PTCL patients achieving CR1 following induction therapy, consolidative ASCT does not extend overall survival and progression-free survival compared to observation. Similarly, consolidative ASCT also failed to reduce cumulative incidence of relapse. We favor proceeding to observe and wait because of high toxic of hematopoietic stem cell transplantation. However, The finding still needs to be confirmed in a larger, prospective study. Table 1 Disclosures No relevant conflicts of interest to declare.

Download Full-text

Impact of age on survival in radioiodine refractory differentiated thyroid cancer patients

Acta Endocrinologica ◽

10.1530/eje-20-1073 ◽

2021 ◽

Vol 184 (5) ◽

pp. 667-676

Author(s):

C Saïe ◽

J Wassermann ◽

E Mathy ◽

N Chereau ◽

L Leenhardt ◽

...

Keyword(s):

Overall Survival ◽

Prognostic Factors ◽

Statistical Difference ◽

Differentiated Thyroid Cancer ◽

Progressive Disease ◽

Progression Free Survival ◽

Single Center ◽

Poor Survival ◽

Free Survival ◽

Secondary Endpoints

Objective The objectives of our study were to analyze the influence of age on the survival of patients with RAIR-DTC and to determine their prognostic factors according to age. Methods This single-center, retrospective study enrolled 155 patients diagnosed with RAIR-DTC. The primary end point was overall survival (OS) according to different cutoff (45, 55, 65, 75 years). Secondary endpoints were progression free survival (PFS) and prognostic factors in patients under and over 65 years. Results Median OS after RAIR diagnosis was 8.2 years (95% IC: 5.3–9.6). There was no difference according to age with a 65 (P = 0.47) and 55 years old cutoff (P = 0.28). Median OS improved significantly before 45 years old (P = 0.0043). After 75 years old, median OS significantly decreased (P = 0.0008). Median PFS was 2.1 years (95% CI: 0.8–3) in patients < 65 years old, and 1 year in patients ≥ 65 years old (95% CI: 0.8–1.55) with no statistical difference (P = 0.22). There was no impact of age on PFS with any cutoff. In both groups, progressive disease despite 131I treatment reduced OS. In patients < 65 years old, an interval of less than 3 years between the initial diagnosis and the diagnosis of RAIR metastatic disease was predictive of poor survival. In patients > 65 years old, the presence of a mediastinum metastasis was a significant factor for mortality (HR: 4.55, 95% CI: 2.27–9.09). Conclusion In RAIR-DTC patients, a cut-off age of 65 years old was not a significant predictive factor of survival. Forty-five and 75-years-old cutoff were predictive for OS but not PFS.

Download Full-text

Comparison of 140mg/m2 vs 200mg/m2 Dose of Melphalan in Myeloma Autograft - a Single Centre Experience from Chennai, India

Blood ◽

10.1182/blood-2020-138507 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 34-35

Author(s):

Kishore Kumar ◽

Chezhian Subash

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Stem Cell ◽

Complete Remission ◽

Relapse Rate ◽

Cumulative Incidence ◽

Progression Free Survival ◽

Free Survival ◽

Gram Negative ◽

Co Morbidity

Introduction: - Melphalan at a dose of 200mg/m2 is considered the standard autograft dose in patients with multiple myeloma without significant co-morbidity. This drug was formulated in the early years before the era of novel agent induction and maintenance. Considering the deeper remission of novel agents and prevailing refractory gram-negative sepsis in most Indian setups, we compared 140mg/m2 (MEL140)vs. 200mg/m2(MEL200) of Melphalan in Indian myeloma patients who achieved a complete remission before transplant without having any significant co-morbidity. Methods and results: - We analysed myeloma autograft patients from September 2014 to August 2017. 42 patients received MEL200, and 43 patients received MEL140. Diabetes on oral medications was randomised equally on both sides. The median age of patients in MEL200 was 52 years, and MEL140 was 53.6 years. There were 60% and 55% of males in MEL200 vs. MEL140, respectively. ISS-III patients was 48% and 49% in MEL200 vs. MEL140, respectively. The standard induction regimen was three to four cycles of RvD chemotherapy. Around 16% of patients in the MEL140 group had a creatinine clearance between 30-50ml/min. The mobilisation regimen followed was five days of GCSF based mobilisation. The stem cell cut-off was kept to a minimum of 2 x 106/CD34+ve cells/kg body weight. Overall, 12% of patients in both groups needed a second-day stem cell collection. Three-year overall survival, progression-free survival, the incidence of relapse, rate of refractory sepsis, the time difference in hematopoietic recovery, and secondary cancers were compared between two groups. In outcome analysis, there was no transplant-related mortality in both groups. The mean day of engraftment was around Day +9 in MEL140 vs. Day +11 in MEL200. The rate of Gram-Negative Bacilli sepsis was around 14% in MEL140 vs. 27% in Mel200 (p 0.02). These findings were reflected in the use of high-end antibiotics like Colistin and Fosfomycin in such patients. There was a delay in engraftment, which may have been confounded by sepsis. The median progression-free survival was 26.1 months in MEL200and 27.2 months in the MEL140 group. The cumulative incidence of relapse at three years was not significantly different between the Mel200 (33.3%) and Mel140 (34.9%) groups. The adjusted HR for relapse was 0.98. Subgroup analysis suggests that in overall survival, progression-free survival, and cumulative incidence of relapse, there was no significant advantage associated with Melphalan 200 mg/m2. Age, renal status, proteasome inhibitor treatment, gender, or Karnofsky score did not interact with overall/progression-free survival or relapse rate in the two melphalan dose groups. One patient in the MEL200 group developed -5q deletion Myelodysplastic syndrome after five years of transplant. Discussion: This study was conducted taking into account the changing scenario in myeloma induction and maintenance to novel agents and increasing rate of resistant gram-negative sepsis in Indian febrile neutropenic patients. As we can achieve a deeper remission before transplant, we formulated to compare lower dose melphalan to prevent a stormy post-transplant course and prevent patients succumbing to sepsis. This may not be an issue in western countries where gram-negative sepsis rates are lower. The biggest worry for us is not compromising the myeloma outcome due to lower doses of Melphalan in fit patients who achieve complete remission. This study concluded that there is not much of a difference in overall survival, Progression-free survival, and cumulative incidence of relapse at three years among MEL200 vs. MEL140. Conclusion: - We conclude that Melphalan autograft at a dose 140mg/m2 can achieve comparable responses to 200mg/m2 in Indian myeloma patients who are taken to transplant post complete remission. We need a more prominent multicentric study and a longer follow-up to recommend MEL140 as a standard of care in Indian settings. References: Auner HW et al. Melphalan 140 mg/m2 or 200 mg/m2 for autologous transplantation in myeloma: results from the Collaboration to Collect Autologous Transplant Outcomes in Lymphoma and Myeloma (CALM) study. A report by the EBMT Chronic Malignancies Working Party. Haematologica. 2018;103(3):514-521.Saunders IM et al A lower dose of Melphalan (140 mg/m2) as preparative regimen for multiple myeloma in patients >65 or with renal dysfunction. Blood. 2013;122:5536. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Very Elderly Patients with Myeloproliferative Neoplasms: Phenotypic Distinctions and Prognostic Determinants of Complications and Mortality

Blood ◽

10.1182/blood-2021-145131 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2572-2572

Author(s):

Judith Jolin ◽

Michael Harnois ◽

Luigina Mollica ◽

Pierre Laneuville ◽

Robert Delage ◽

...

Keyword(s):

Bone Marrow ◽

Overall Survival ◽

Arterial Thrombosis ◽

Smoking Status ◽

Myeloproliferative Neoplasms ◽

Very Elderly ◽

Bone Marrow Biopsies ◽

Free Survival ◽

Younger Patients ◽

History Of

Abstract Background and methods: Increasing life expectancy has had the impact of increasing the proportion of patients with myeloproliferative neoplasms (MPN) aged ≥75 years (very elderly patients; VEP). However, few studies have evaluated the phenotype and prognostic factors specific to this population. This is a retrospective multicenter chart review (11 Quebec centers) of VEP with polycythemia vera (PV), essential thrombocytosis (ET), and myelofibrosis (MF) diagnosed between 1978 and 2019, enrolled in the CML-MPN Quebec Research Group registry. All diagnoses were made according to World Health Organization 2016 criteria (Blood. 2016;127:2391), with exemption of bone marrow biopsies in select patients. Standard statistical methods were used for all analyses. Results: Of the 753 patients studied in the registry, 114 patients (15%) were ≥75 years old (VEP) (Table 1). These subjects had a median age of 79 years (range 75-95) with incidence of PV, ET and MF of 38%, 51% and 11% respectively. Compared to patients <75 years old, VEP were less likely to be male (35% vs 45%, p = 0.05), had more frequent and higher levels of leukocytosis (11.4 vs 9.7 x 10 9 / L, p <0.0001), were more frequently "triple negative" and less commonly CALR-mutated (p = 0.0005), and presented significantly higher allelic burdens (45% vs 36%, p = 0.03). VEP also had more cardiovascular comorbidities (p <0.0001) and were more often classified as "high risk" (86% vs. 43%, <0.0001). A history of arterial thrombosis prior to/at diagnosis was more common in VEP vs younger patients (14% vs 7.2%, p = 0.02), as was a global history of arterial and/or venous thrombosis at any time during the follow up (25% vs 18%, p = 0.05). Sites of venous events were specifically skewed towards lower extremity deep vein thrombosis in VEP (75%) vs variously distributed in younger patients (p = 0.05). Bleeding rates were similar among the two groups (16% VEP and 17% non-VEP, p = 0.7) while fewer fibrotic (3% vs 8%, p = 0.03) and leukemic transformations (0 vs 2%, p = 0.04) were recorded in VEP. Significantly fewer bone marrow biopsies were performed in VEP (41% versus 54%, p = 0.01). This cohort was, however, more likely to receive cytoreductive therapy (76% vs 67%, p = 0.05), predominantly hydroxyurea (70% vs 59%, p = 0.02). Multivariate analysis revealed the presence of splenomegaly (HR 4.5; 1.2-17.1, p = 0.03) and smoking status (active/former vs never smokers) (HR 5.2; 1.1-24.9, p = 0.03) as predictors of shortened overall survival for the VEP population (Table 2). It also disclosed higher leukocyte count (p = 0.005) and the presence of diabetes mellitus (p = 0.05) as significant risk factors for shortened hemorrhage-free survival. Platelet count (p = 0.03) and smoking status (p = 0.02) were found to be significant determinants of thrombosis-free survival in univariate analysis but did not maintain their significance in multivariate testing. Kaplan-Meier survival data examining age-stratified outcomes in VEP vs younger patients revealed significantly shorter overall survival in VEP (14.2 years vs not reached, p < 0.0001) (Figure 1). The VEP cohort also displayed significantly reduced arterial thrombosis-free survival (incidence of 6.1% vs 3.9%, p = 0.01). There was no significant difference in event data for venous thrombosis-free (4% in both, p = 0.2) and myelofibrosis-free (2.6% versus 7.8%, p = 0.6) survival. Conclusion: This data addressing VEP with MPN exposes, for the first time: i) a characteristic phenotype (predominantly female, higher leukocyte counts, higher allele burden), ii) distinct adverse outcome patterns, particularly with regard to arterial thrombosis, and iii) unique and independent prognostic factors for survival, suggesting that VEP with MPN constitute a biologically, phenotypically, and prognostically distinct population. Figure 1 Figure 1. Disclosures Busque: Novartis: Consultancy. Szuber: Novartis: Honoraria.

Download Full-text

Extending Metronomic Therapy to 28 Days (metro28) for Relapsed Refractory Multiple Myeloma (RRMM)

Blood ◽

10.1182/blood.v126.23.5395.5395 ◽

2015 ◽

Vol 126 (23) ◽

pp. 5395-5395

Author(s):

Xenofon Papanikolaou ◽

Carolina Schinke ◽

Sharmilan Thanendrarajan ◽

Adam Rosenthal ◽

Nathan Petty ◽

...

Keyword(s):

Overall Survival ◽

Board Of Directors ◽

Clinical Outcomes ◽

Research Funding ◽

Progression Free Survival ◽

Advisory Board ◽

University Of Arkansas ◽

Medical Sciences ◽

Advisory Committees ◽

Free Survival

Abstract Introduction: Despite the enormous progress in MM therapy brought about by the rapid development of many novel agents, many patients end up with limited treatment options. We have previously reported on the efficacy and safety of metro16 in RRMM (Papanikolaou, Haematology 2013). Here we are reporting on an extension of such treatment to 28 d (metro28). Patients and Methods: The treatment consisted of a cycle of 28d continuous iv infusions of ADR and DDP each at 1mg/m2/d, along with thalidomide 50 to 100mg/d x 28; bortezomib 0.8 to 1.0mg/m2 on days 1, 4, 7, 10, 13, 16, 19, 22, 25, 28; DEX 8 to 12mg on days 1-4, 7-10, 13-16, 19-22, 25-28; some patients also received vincristine 0.07mg flat dose by CI for 28 days. This was off-protocol therapy that patients provided written informed consent for. The IRB permitted data retrieval and analysis. Results: 150 patients were identified, virtually all had received prior tandem transplants, bortezomib, lenalidomide, carfilzomib and pomalidomide. The median age was 64yr; B2M was elevated >=3.5mg/L in 48%, abnormal cytogenetics (CA) were present in 86%, and 44% had GEP70-defined high risk MM. Figure 1 portrays clinical outcomes. As of April 2015, 60 patients had died, and the 2-yr OS estimate was 45% (Figure 1A); the 6-mo PFS estimate was 31% although 15% had no progression at 18mo (Figure 1B). Analysis by GEP70 and GEP5 risk revealed 18-mo OS estimates of 80% among the 53 patients with low risk in both models, whereas the presence of high risk (HRMM) in either model conferred a significantly reduced 18-mo OS estimate of 25% (p<0.0001) (Figure 1C). On Cox regression analysis, OS was independently adversely affected by GEP5 HRMM (47%, HR=3.43, p<0.001), LDH >=ULN (25%, HR=3.46, p<0.001), low albumin (39%, HR=2.68, p=0.003), B2M >=3.5mg/L (51%, HR+2.63, p=0.014) and thrombocytopenia <50,000/uL (15%, HR=2.3, p=0.043). GEP5 HRMM was the sole adverse variable affecting PFS (HR=2.37, p<0.001). Most patients received metro28 in the outpatient setting, and side effects were mild. Conclusion: Metro28 represents a well-tolerated additional tool in the treatment armamentarium for RRMM. Figure 1. Clinical outcomes A: Overall survival B: Progression-free survival C: Overall survival according to GEP70 and GEP5 risk designations Figure 1. Clinical outcomes. / A: Overall survival. / B: Progression-free survival. / C: Overall survival according to GEP70 and GEP5 risk designations Figure 2. Figure 2. Figure 3. Figure 3. Disclosures Schinke: University of Arkansas for Medical Sciences: Employment. Thanendrarajan:University of Arkansas for Medical Sciences: Employment. Rosenthal:Cancer Research and Biostatistics: Employment. Petty:University of Arkansas for Medical Sciences: Employment. Zangari:University of Arkansas for Medical Sciences: Employment; Onyx: Research Funding; Millennium: Research Funding; Novartis: Research Funding. Heuck:Celgene: Consultancy; Foundation Medicine: Honoraria; Janssen: Other: Advisory Board; University of Arkansas for Medical Sciences: Employment; Millenium: Other: Advisory Board. van Rhee:University of Arkansa for Medical Sciences: Employment. Epstein:University of Arkansas for Medical Sciences: Employment. Yaccoby:University of Arkansas for Medical Sciences: Employment. Morgan:Weismann Institute: Honoraria; CancerNet: Honoraria; MMRF: Honoraria; University of Arkansas for Medical Sciences: Employment; Bristol Myers Squibb: 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; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Davies:University of Arkansas for Medical Sciences: Employment; Celgene: Consultancy; Janssen: Consultancy; Millenium: Consultancy; Onyx: Consultancy. Barlogie:University of Arkansas for Medical Sciences: Employment.

Download Full-text

Related Nonmyeloablative Haploidentical (mini-haplo) Blood or Marrow Transplantation (BMT) with High-Dose Post-Transplant Cyclophosphmade (PTCy) for Acute Myeloid Leukemia (AML): Donor Age Impacts Outcome

Blood ◽

10.1182/blood.v126.23.151.151 ◽

2015 ◽

Vol 126 (23) ◽

pp. 151-151 ◽

Cited By ~ 4

Author(s):

Margaret M. Showel ◽

Ephraim J. Fuchs ◽

Ravi Varadhan ◽

Mark J. Levis ◽

Richard J. Jones

Keyword(s):

Overall Survival ◽

High Risk ◽

Cumulative Incidence ◽

Graft Failure ◽

Progression Free Survival ◽

Donor Age ◽

Free Survival ◽

Entire Cohort ◽

Poor Risk ◽

Cd34 Cells

Abstract Introduction Allogeneic BMT is often the only curative option for poor-risk AML. Not only does mismatched BMT circumvent the limited availability of HLA matched donors, but it also allows a wider choice of potential donors. We report an analysis of mini-haplo BMT in 93 patients with high-risk AML. In light of emerging data regarding the influence of donor age on outcome of BMT, we specifically studied the impact of donor age on outcome. Methods We conducted a retrospective review of all adult patients at Johns Hopkins, who received a mini-haplo BMT for AML between January of 2003 and February of 2013. Patients received Cy (14.5 mg/kg/day IV D -6,-5), fludarabine (30mg/mg2/day IV D -6 to -2), and 200 cGy total body irradiation on day -1. GVHD prophylaxis was PTCy (50 mg/kg D 3, 4), mycophenolate mofetil, and tacrolimus. Progression-free (PFS) and overall survival (OS) were evaluated based on Kaplan-Meier method. The cumulative incidence of GVHD and non-relapse mortality (NRM) were assessed via Gray's approach.. Results The median age of the 93 AML patients was 54 (range 24-73). For the 47 patients transplanted in CR1, the median time to BMT from CR1 was 84 (range 11-347) days. Median follow-up was 44 (range 5-117) months. Successful engraftment with sustained donor chimerism was achieved in 80 of 89 evaluable patients by day 60; two additional patients experienced secondary graft failure. These 11patients who developed graft failure had donors who were older, with a median age of 49 (range 35-63) versus 38 (range 14-68) years (p=0.03), and they received allografts with significantly fewer CD34+ cells, with a median of 2.5x106/kg compared to 4.5x106 cells/kg (p=0.01). The 13 allografts with ≤ 2.5x106 CD34+ cells/kg were associated with 6 of the primary graft failures compared to only 5 graft failures in the 80 patients receiving > 2.5x106 CD34+ cells/kg (p=0.0004). Moreover, the donors of the 13 allografts with ≤ 2.5x106 CD34+ cells/kg had a median age of 52 compared to age 39 for donors of the 80 grafts with > 2.5x106 CD34+ cells/kg (p=0.04). The overall cumulative incidence (CI) of grade II-IV and III-IV aGVHD and cGVHD was 24% (95% CI 15-33%), 8% (2-13%), and 17% (9-25%), respectively. The CI of NRM was 11% (4-17%). The overall CI of relapse was 54% (95%CI 43-65%). The 4-year actuarial OS and PFS were 47% (95% CI 37-59%) and 35% (95%CI 26-48%) (Fig 1). Patient age did not have a significant impact on survival. However, there was a trend toward better survival with younger donors. For patients with donors ≤ 55 years, the median OS was 63 (range 1-118) months compared to 13 (range 1-65) months (p=0.14) (Fig 2). Discussion Mini-haplo BMT offers a potentially curative option for poor-risk AML patients lacking matched donors. GVHD and NRM rates were low. The time to BMT in our patients was similar to those reported for matched sibling donors (Walter, et al, Blood. 2013; 122: 1813-1821) and shorter than those for MUD transplants, (Rollig, et al, JCO. 2015; 33: 403-410), an important consideration because over one-third of pts with high-risk AML relapse within 4 months of initial therapy. Graft failure, a concern with mismatched BMT, appears to be in part related to donor age, with older donors providing inferior quality allografts. Survival was also inferior with the use of older donors. Our data strongly suggest that no AML patient in need of BMT should be denied the procedure for lack of a suitable donor. Moreover, the use of mismatched donors allows donor selection based on donor characteristics, such as age, that have the potential to improve outcomes. Figure 1. Overall and progression-free survival of the entire cohort Figure 1. Overall and progression-free survival of the entire cohort Figure 2. Overall survival by donor age Figure 2. Overall survival by donor age Disclosures No relevant conflicts of interest to declare.

Download Full-text

Differences in survival between usual practice and clinical trial participants in advanced NSCLC by age.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e20515 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e20515-e20515

Author(s):

Ana Laura Ortega Granados ◽

Nuria Cárdenas Quesada ◽

Capilla de la Torre Cabrera ◽

Mónica Fernández Navarro ◽

María Ruiz Sanjuan ◽

...

Keyword(s):

Overall Survival ◽

Median Overall Survival ◽

Case Control Study ◽

Advanced Nsclc ◽

Progression Free Survival ◽

Case Control ◽

Free Survival ◽

Younger Patients ◽

Usual Clinical Practice ◽

Control Study

e20515 Background: It is known that outcome of patients included in clinical trials have a better outcome than patients treated with standard therapy. This is a retrospective case-control study of outcome of patients with stage III and IV non-small cell lung cáncer (NSCLC) recruited in clinical trials vs advanced NSCLC patients in usual clinical practice in our institution. Methods: We performed a case-control study matching all patients participating in trials with chemotherapy and/or TKis (immunotherapy was not included) in a 5 year period (January 2010-November 2014) in 1st line setting, matching them in a ratio 1:2 with individuals in usual clinical practice. There were 36 patients in trials and 72 patients treated by our protocol. Cases were matched by age ( < 65 and > 65), histology (adenocarcinoma and squamous), EGFR status (mutated and wild-type). All patients were WHO performance status 0-1. Results: Patients in each group were matched for stage, histological subtype, previous surgery and systemic therapy. Median follow up for patients treated on a trial was 3.3 years, compared with 2.9 years for matched patients who received standard 1st line therapy. Median overall survival for patients included a trial was 19.6 months, and 15.7 months for control group. The difference between groups was not significant (Log rank test, HR 0.81, 95% CI: 0.42 to 1.30, p = 0.53). Median overall survival in younger patients in trials ( < 65) was 19.3 months, and in elderly patients was 19.8 months. The median progression-free survival in the two groups was 6.8 and 5.5 months respectively (HR 0.72, 95% CI 0.30 to 1.43, p = 0.21). Conclusions: In our institution, we didn’t found significant differences for overall survival or progression-free survival, but there is a trend for a better outcome for those items. Benefit seems to be similar in younger patients than in older patients, so this encourages recruiting of selected elderly patients.

Download Full-text