Influence of treatment intensity and medical comorbidities in older adults with peripheral T cell lymphoma.

We conducted a population-based study of patients >65 years, diagnosed 2008-2017, with peripheral T-cell lymphoma (PTCL) using SEER-Medicare. Associations between PTCL subtype, treatment regimen, comorbidity, and mortality were assessed using the Kaplan-Meier method and multivariable Cox regression. Amongst the 2,546 patients, the median age was 77 years (interquartile range, 71-83). 5-year overall survival (OS) ranged from 22.2% to 37.3% depending on PTCL subtype. The most common frontline regimen was cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). 5-year OS rate was 47.0% for patients treated with etoposide + CHOP (N = 67; CHOEP), 33.7% for those treated with CHOP (N = 732), and 23.8% for patients treated with non-anthracycline-containing regimens (N = 105; p < 0.001). In patients without comorbidities, CHOEP remained independently associated with improved OS (HR 0.52, 95% CI,0.30-0.91). Median OS was 1.2 years from initiation of second-line therapy (N = 228) independent of treatment regimen. Frontline but not second-line treatment regimen is associated with OS in older patients with PTCL.

Cost of Disease Progression in Diffuse Large B-Cell Lymphoma After Frontline Treatment With Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone.

BACKGROUND: In recent years, novel agents have become available to treat relapsed/refractory diffuse large B-cell lymphoma (DLBCL); the impact of such agents on treatment costs has not been formally studied. We present results from 2 independent, retrospective, real-world cohort analyses to determine the cost of disease progression after first-line rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). MATERIALS AND METHODS: Analyses were conducted using the IQVIA PharMetricsⓇ Plus claims database and the Surveillance, Epidemiology, and End Results registry-Medicare-linked database (SEER-Medicare) and included patients ≥18 years and ≥66 years, respectively. "No progression" was defined as no second-line therapy for ≥2 years after the end of first-line R-CHOP and "treated progression" as initiating a second-line therapy within 2 years following the end of first-line R-CHOP. Analyses were adjusted for baseline covariates, and per-patient-per-month (PPPM) costs were compared between progressors and nonprogressors. RESULTS: The IQVIA PharMetrics Plus analysis (January 1, 2010-June 30, 2018) included 871 patients (nonprogressors, n = 725; progressors, n = 146), including 10 patients who received chimeric antigen receptor T-cell therapy (CAR-T). Treated progression was associated with significantly higher adjusted PPPM costs than no progression ($10,554 vs. $1561, P < .001). The SEER-Medicare analysis (January 1, 2010-December 31, 2017) included 4099 patients (nonprogressors, n = 3389; progressors, n = 710), including 12 patients receiving CAR-T. Treated progression was associated with significantly higher adjusted PPPM costs than no progression ($10,928 vs. $2902, P < .001). CONCLUSION: Treated progression of DLBCL increases adjusted PPPM costs by over $8000 compared with no progression.

The Impact of Sequence of Therapy for Older Patients With Follicular Lymphoma: SEER-Medicare Analysis.

BACKGROUND: One key clinical challenge remains in how to sequence treatments in follicular lymphoma (FL). The chemoimmunotherapy rituximab cyclophosphamide, doxorubicin, vincristine (Oncovin), and prednisone (R-CHOP) has been a standard treatment option for two decades. However, there are limited data to suggest in which line R-CHOP should be used for older patients. PATIENTS AND METHODS: We leveraged population-based surveillance, epidemiology, and end results-medicare data and identified 675 patients aged ≥65 years newly diagnosed with FL from 2000 to 2009 who received R-CHOP in either the first or second line. We estimated restricted mean survival time using Kaplan-Meier curves, propensity scores (PS), and regression models comparing patients who received R-CHOP as a first versus second line. RESULTS: We found that patients who received R-CHOP as first line had significantly longer 9-year RMST than those who received R-CHOP in the second line using Kaplan-Meier curves (P = .01), PS stratification (P = .002), PS matching (P = .005), and the inverse of PS as the treatment weight (P < .0001). The subgroup analyses using linear regression models showed that the 9-year restricted mean survival time of patients who received R-CHOP as the first line was longer in patients aged ≥80 years (P = .002) and with histological grade 1 or 2 (P = .02), compared to those who received R-CHOP as second line. CONCLUSION: R-CHOP given in the first line was associated with longer overall survival compared to R-CHOP given as second line for older patients with FL.

[Clinical assessment of moderate-dose glucocorticoid in the treatment of recurrence of primary nephrotic syndrome in children: a prospective randomized controlled trial]. / ä¸­ç­‰å‰‚é‡ç³–çš®è´¨æ¿€ç´ æ²»ç–—æ¿€ç´ æ•æ„Ÿè‚¾ç— ç»¼åˆå¾å¤å‘æ‚£å„¿çš„å‰çž»æ€§éšæœºå¯¹ç §ç ”ç©¶.

OBJECTIVES: To study the clinical effect and adverse drug reactions of different doses of glucocorticoid (GC) in the treatment of children with recurrence of steroid-sensitive nephrotic syndrome (SSNS). METHODS: A total of 67 children who were hospitalized and diagnosed with SSNS recurrence in the Department of Nephrology, Children's Hospital, Capital Institute of Pediatrics, from November 2017 to December 2019 were enrolled. They were randomly divided into a moderate-dose GC group (32 children) and a full-dose GC group (35 children). The two groups were compared in terms of urinary protein clearance, recurrence rate within 6 months, and incidence rate of GC-associated adverse reactions. RESULTS: There was no significant difference in the urinary protein clearance rate between the moderate-dose GC and full-dose GC groups (91% vs 94%, P>0.05). There was also no significant difference in the recurrence rate within 6 months between the two groups (41% vs 36%, P>0.05). At 6 months of follow-up, compared with the full-dose GC group, the moderate-dose GC group had a significantly lower cumulative dose of prednisone [(87±18) mg/kg vs (98±16) mg/kg, P=0.039] and a significantly lower proportion of children with an abnormal increase in body weight (6% vs 33%, P=0.045). The logistic regression analysis showed that prednisone dose ≥10 mg/alternate day at enrollment was a risk factor for recurrence within 6 months in children with SSNS (P=0.018). CONCLUSIONS: For children with SSNS recurrence, moderate-dose GC has similar effects to full-dose GC in the remission induction rate and the recurrence rate within 6 months, with a lower cumulative dose and fewer GC-associated adverse reactions within 6 months than full-dose GC.

Burden of Illness and Treatment Patterns in Second-line Large B-cell Lymphoma.

PURPOSE: This study examined real-world treatment patterns with curative intent, adverse events, and health care resource utilization and costs in patients with relapsed or refractory large B-cell lymphoma (LBCL) to understand the unmet medical need in the United States. METHODS: Adult patients with ≥2 LBCL diagnoses between January 1, 2012, and March 31, 2019, were identified (index date was the date of the earliest LBCL diagnosis) from MarketScan® Commercial and Medicare Supplemental Databases. Patients had ≥1 claim for any LBCL treatment, ≥6 months of data before (baseline) and ≥12 months of data after (follow-up period) the index date, and no baseline LBCL diagnosis. Treatment patterns, adverse events, and all-cause and LBCL-related health care resource utilization and costs were examined. All patients had received first-line therapy of cyclophosphamide, doxorubicin, vincristine, and prednisone with or without rituximab; etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin hydrochloride with or without rituximab; or regimens with anthracycline and second-line therapy with stem cell transplant (SCT)-intended intensive therapy or platinum-based chemotherapy. Patients who received an SCT-intended second-line regimen or received an SCT regardless of second-line regimen were considered SCT eligible. FINDINGS: A total of 188 patients met the criteria of eligibility for SCT. Among the 119 patients who received a second-line regimen intended for SCT, only 22.7% received an SCT. Patients eligible for SCT started first-line therapy within 1 month of their LBCL index date, and the mean duration of first-line therapy was 4.1 months. The mean gap in therapy between first- and second-line therapy was 6.6 months, and the mean duration of second-line therapy was 3.0 months. During the second-line therapy treatment window (mean duration with SCT, 12.4 months; mean duration without SCT, 4.8 months), the most common regimens for patients eligible for SCT were ifosfamide, carboplatin, and etoposide with or without rituximab and gemcitabine and oxaliplatin with or without rituximab; the top 4 most common treatment-related adverse events were febrile neutropenia (56.4%), anemia (49.5%), thrombocytopenia (42.6%), and nausea and vomiting (36.2%), which were similar regardless of receipt of SCT; mean (SD) per-patient-per-month all-cause costs were $46,174 ($49,057) for patients with SCT and $45,780 ($52,813) for patients without SCT. IMPLICATIONS: Treatment patterns among patients with relapsed or refractory LBCL eligible for SCT were highly varied. Only 22.7% of patients who received an SCT-preparative regimen ultimately received SCT, which highlights the magnitude of unmet needs in this population. The occurrence of treatment-related adverse events was similar regardless of SCT status. Per-patient-per-month all-cause costs were also similar with upfront SCT costs averaged during a longer follow-up.

Imatinib Mesylate for the Treatment of Canine Mast Cell Tumors: Assessment of the Response and Adverse Events in Comparison with the Conventional Therapy with Vinblastine and Prednisone.

Mast cell tumors (MCTs) are common neoplasms in dogs, and treatments for these diseases include surgery, polychemotherapy and targeted therapy with tyrosine kinase inhibitors. This study aimed to evaluate the response and the adverse events of treatment with imatinib mesylate (IM) compared to conventional therapy using vinblastine and prednisolone (VP) in canine cutaneous MCTs. Twenty-four dogs were included in the study; 13 animals were treated with IM and 11 with VP. Tumor tissue samples were submitted for histological diagnosis, grading and KIT immunostaining. The response to treatment was assessed by tomographic measurements according to VCOG criteria. Adverse events were classified according to VCOG-CTCAE criteria. The IM and VP groups had dogs with similar breeds, gender, ages, MCT localization, WHO stages and lymph node metastasis profiles. Most MCTs were grade 2/low and had KIT- patterns 2 and 3. The objective response rate (ORR) was significantly higher (30.79%) in the IM group then in VP group (9.09%). Adverse events (AE) in IM group were all grade 1, significantly different from VP. In conclusion, IM presented better ORR and less severe adverse events when compared to VP, representing a suitable option for the treatment of low-grade canine MCTs.

Conversion to supportive care with biosimilar pegfilgrastim-cbqv enables budget-neutral expanded access to R-CHOP treatment in non-Hodgkin lymphoma.

This pharmacoeconomic simulation (1) assessed the cost-efficiency of converting a panel of 20,000 patients at risk of chemotherapy-induced (febrile) neutropenia (CIN/FN) from reference pegfilgrastim to biosimilar pegfilgrastim-cbqv; (2) estimated how savings can be used to provide budget-neutral expanded access to R-CHOP therapy for non-Hodgkin lymphoma patients; and 3) determined the number-needed-to-convert (NNC) to purchase one additional dose of R-CHOP (US payer perspective). Model inputs included biosimilar conversion from pre-filled syringe [PFS] or on-body injector [OBI] reference pegfilgrastim; age-proportional blended costs for reference pegfilgrastim PFS and OBI, pegfilgrastim-cbqv and R-CHOP; medication administration costs; biosimilar conversion rates of 10-100 %; and 1-6 cycles of prophylaxis. Cost-savings were used to estimate the number of doses of R-CHOP that could be purchased and the NNC to purchase one additional dose. Converting a panel of 20,000 patients requiring CIN/FN prophylaxis to biosimilar pegfilgrastim-cbqv from a low of 1 cycle and 10 % conversion to a high of 6 cycles and 100 % conversion yielded savings from $1,567,195 to $96,668,126. The budget-neutral acquisition of R-CHOP doses afforded by these savings ranged from 227 to 13,999 doses, the latter enabling 2333 patients to receive 6 cycles of R-CHOP treatment with no additional cost to the payer. These results are achieved if all 20,000 panel patients requiring GCSF support are prophylacted with biosimilar pegfilgrastim-cbqv for 6 cycles, yielding an NNC of 1.43 patients per additional R-CHOP dose. This simulation underscores the clinic-economic benefit of prophylaxis with biosimilar growth factor and pegfilgrastim-cbqv specifically.

Adverse Events and Economic Burden Among Patients Receiving Systemic Treatment for Mantle Cell Lymphoma: A Real-World Retrospective Cohort Study.

BACKGROUND/AIM: Limited published real-world data describe adverse events (AEs) among patients treated for mantle-cell lymphoma (MCL). The aim of this retrospective study was to describe treatment patterns, AEs, and associated healthcare costs. PATIENTS AND METHODS: Patients had two or more claims coded for MCL diagnosis, the first claim date (07/01/2012-05/31/2017) was the index date. Patients with pre-index MCL diagnosis or systemic treatment, or hematopoietic stem cell transplantation were excluded. Cohorts by regimen were followed for up to three lines of therapy. RESULTS: Patients (n=395; median age 72 years; 31% female) were observed over a total of 576 lines of therapy, the most common being bendamustine plus rituximab; rituximab monotherapy; R-CHOP; and ibrutinib. The most frequent AEs were hypertension (40.5%), anemia (37.7%), and infection (36.1%). However, hepatotoxicity ($19,645), stroke ($18,893), and renal failure ($9,037) were associated with the highest medical costs per patient per month. CONCLUSION: Among patients receiving common systemic treatments for MCL, AEs occurred frequently; some imposed substantial inpatient care costs.

Identifying a Response for the Systemic Lupus Erythematosus Disease Activity 2000 Glucocorticoid Index.

OBJECTIVE: To compare the performance of the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and the SLEDAI-2K Glucocorticoids (SLEDAI-2KG) indices in identifying responders to standard of care therapy. METHODS: Data from adult patients seen between 1995 and 2018 at the University of Toronto Lupus Clinic were analyzed. Patients with active disease (SLEDAI-2K score ≥6) and receiving prednisone ≥5 mg/day, and with a follow-up visit at 9 months, were studied. Response to standard of care therapy at first follow-up visit was assessed using the SLEDAI-2K and SLEDAI-2KG. The performances of the SLEDAI-2K and SLEDAI-2KG were compared using a cutoff point of 4. RESULTS: In a cohort of 188, the majority of patients were female (86.0%) and White (47.9%). Of 188 patients, 145 (77.1%) were responders and had a decrease in SLEDAI-2K score of ≥4. The SLEDAI-2KG identified 142 (97.9%) responders among the SLEDAI-2K responders. More importantly, the SLEDAI-2KG identified 11 (25.6%) additional responders among SLEDAI-2K nonresponders (n = 43). This resulted from the ability of the SLEDAI-2KG to account for the decrease in glucocorticoids dose. CONCLUSION: The SLEDAI-2KG provides a novel concept for the assessment of lupus disease activity while accounting for glucocorticoids dosage to reflect on disease activity overall at a particular visit. The SLEDAI-2KG accounts for the disease activity for each descriptor while also accounting for the current glucocorticoids dosage. The SLEDAI-2KG adds 1 additional variable (glucocorticoids dosage) to the SLEDAI-2K, which could alter response rates in drug trials and observational studies.

Outcomes of treatment with CHOP and EPOCH in patients with HIV associated NHL in a low resource setting.

BACKGROUND: The optimal chemotherapy regimen for treating HIV associated NHL in low resource settings is unknown. We conducted a retrospective study to describe survival rates, treatment response rates and adverse events in patients with HIV associated NHL treated with CHOP and dose adjusted-EPOCH regimens at the Uganda Cancer Institute. METHODS: A retrospective study of patients diagnosed with HIV and lymphoma and treated at the Uganda Cancer Institute from 2016 to 2018 was done. RESULTS: One hundred eight patients treated with CHOP and 12 patients treated with DA-EPOCH were analysed. Patients completing 6 or more cycles of chemotherapy were 51 (47%) in the CHOP group and 8 (67%) in the DA-EPOCH group. One year overall survival (OS) rate in patients treated with CHOP was 54.5% (95% CI, 42.8-64.8) and 80.2% (95% CI, 40.3-94.8) in those treated with DA-EPOCH. Factors associated with favourable survival were BMI 18.5-24.9 kg/m2, (p = 0.03) and completion of 6 or more cycles of chemotherapy, (p < 0.001). The overall response rate was 40% in the CHOP group and 59% in the DA-EPOCH group. Severe adverse events occurred in 19 (18%) patients in the CHOP group and 3 (25%) in the DA-EPOCH group; these were neutropenia (CHOP = 13, 12%; DA-EPOCH = 2, 17%), anaemia (CHOP = 12, 12%; DA-EPOCH = 1, 8%), thrombocytopenia (CHOP = 7, 6%; DA-EPOCH = 0), sepsis (CHOP = 1), treatment related death (DA-EPOCH = 1) and hepatic encephalopathy (CHOP = 1). CONCLUSION: Treatment of HIV associated NHL with curative intent using CHOP and infusional DA-EPOCH is feasible in low resource settings and associated with > 50% 1 year survival.

Assessment of oxidative/anti-oxidative markers and DNA damage profile induced by chemotherapy in algerian children with lymphoma.

The aim of this study was to assess the oxidative stress and the genotoxicity induced by chemotherapy by the determination of plasma malondialdehyde (MDA) level, protein carbonyl (PC) content, superoxide dismutase (SOD) activity and lymphocyte DNA damage in Algerian children with lymphoma. The study population included thirty patients with lymphoma and fifty healthy controls. Patients were treated with 2 courses of OEPA (oncovin 1,5 mg/m2, etoposide 125 mg/m2, prednisone 60 mg/m2 and doxorubicin 40 mg/m2) followed by 2 to 4 courses of COPDAC (cyclophosphamide 500 mg/m2, oncovin 1,5 mg/m2, dacarbazine 250 mg/m2 and prednisone 40 mg/m2). Plasma levels of MDA, PC and SOD were spectrophotometrically measured. DNA damage was assessed by alkaline comet assay in peripheral blood leukocytes. Plasma MDA, PC levels and lymphocyte DNA damage, were found to be significantly higher in lymphoma patients than in controls (p < 0.001). Whereas, SOD activity in lymphoma patients was significantly lower than in healthy controls (p < 0.001). There were significant positive correlations between DNA damage, MDA and PC in patients (r = 0.96, p < 0.001, r = 0.97, p < 0.001, respectively), and negative correlation with SOD (r = -0.87, p < 0.01). Our results indicated that, leukocytes DNA damage and oxidative stress were significantly higher in lymphoma patients, suggesting that the direct effect of chemotherapy and the alteration of the redox balance may influence oxidative/antioxidative status.

Outcomes of bendamustine- or cyclophosphamide-based first-line chemotherapy in older patients with indolent B-cell lymphoma.

Clinical trials comparing bendamustine/rituximab (BR) with cyclophosphamide-based regimens (RCHOP/RCVP) have pooled various histologies of indolent B-cell lymphomas. We examined real-life outcomes of older patients with follicular (FL), mantle cell (MCL), or marginal zone/lymphoplasmacytic lymphoma (MZL/LPL), treated with these first-line regimens. We identified Medicare beneficiaries with FL, MCL, or MZL/LPL, who received either first-line BR or RCHOP/RCVP in 2009-2016, and matched groups using a propensity score. Outcomes of claims-based event-free survival (EFS), overall survival (OS), toxicity, secondary cancers, and costs were compared in the aggregate cohort (N = 2736), and in separately matched histology-specific subcohorts. In the aggregate cohort, EFS was better with BR than with RCHOP/RCVP (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.70-0.87). Acute toxicity was lower with BR, including rates of hospitalizations (33% vs 45%), infections (21% vs 30%), cardiovascular events, and transfusions, yet OS did not differ (HR, 1.03; 95% CI, 0.91-1.17) and Medicare spending was higher. There was no difference in the cumulative incidence of secondary cancers (subhazard ratio, 1.11; 95% CI, 0.83-1.48). The EFS advantage of BR was pronounced in MCL (N = 690; HR, 0.64; 95% CI, 0.54-0.76), but less so in FL (N = 1330; HR, 0.83; 95% CI, 0.69-0.98) and absent in MZL/LPL (N = 574; HR, 0.92; 95% CI, 0.73-1.17). Despite improved EFS and lower toxicity, the shift from RCHOP/RCVP to BR in clinical practice did not improve OS for older patients with indolent B-cell lymphomas. Frequent infections and hospitalizations underscore the need for safer treatment approaches in this population. Secondary cancers do not appear to be increased after BR compared with RCHOP/RCVP.

Treatment patterns, adverse events, healthcare resource use and costs among commercially insured patients with mantle cell lymphoma in the United States.

INTRODUCTION: There are limited data on treatment patterns, adverse events (AEs), and economic burden in younger, commercially insured patients treated for mantle cell lymphoma (MCL). METHODS: Adults with ≥1 treatment for MCL between 1 November 2013-31 December 2017 were identified from IQVIA Real-World Data Adjudicated Claims-US; index date was first treatment. Patients carried ≥1 MCL diagnosis, were newly treated, and were enrolled continuously for ≥12 months prior to and ≥30 days following index. Patients receiving the four most common MCL regimens were included. Measures included frequency of incident AEs, resource use, and costs overall and by number of AEs. Adjusted logistic regression and generalized linear modeling evaluated risk of hospitalization and all-cause costs per patient per month (PPPM). RESULTS: Two thousand five hundred and nine treated patients had a drug-specific code and were classified to a specific treatment regimen. Of those patients, 1785 patients received at least one of the four most commonly used MCL regimens (R-CHOP, rituximab monotherapy, B-R, and ibrutinib) at some point over follow-up (median 23 months). R-CHOP was the most common regimen observed in the first line (26%), followed by rituximab monotherapy (19%), B-R (15%), and ibrutinib (5%). The median age was 57 years; median Charlson Comorbidity Index was 0. Among patients receiving the four most common regimens, 63% of patients experienced ≥1 incident AE (R-CHOP 77%, B-R 58%, and ibrutinib 52%). An increasing number of incident AEs was associated with increased hospitalization risk (odds ratio = 2.4; 95% Confidence Interval [CI] 2.1-2.7) and increased mean costs PPPM (cost ratio = 1.1; 95% CI 1.1-1.2). DISCUSSION: This is the largest study describing treatment patterns and clinical and economic impact of MCL treatment. The most common regimens were R-CHOP, rituximab monotherapy, B-R, and ibrutinib. The majority of treated patients experienced at least one incident AE, with hospitalization risk and all-cause costs increasing as the number of AEs increased.

Cost comparison by treatment arm and center-level variations in cost and inpatient days on the phase III high-risk B acute lymphoblastic leukemia trial AALL0232.

The Children's Oncology Group (COG) develops and implements multi-institutional clinical trials with the primary goal of assessing the efficacy and safety profile of treatment regimens for various pediatric cancers. However, the monetary costs of treatment regimens are not measured. AALL0232 was a COG randomized phase III trial for children with acute lymphoblastic leukemia that found that dexamethasone (DEX) was a more effective glucocorticoid than prednisone (PRED) in patients younger than 10 years, but PRED was equally effective and less toxic in older patients. In addition, high-dose methotrexate (HD-MTX) led to better survival than escalating doses of methotrexate (C-MTX). Cost data from the Pediatric Health Information System database were merged with clinical data from the COG AALL0232 trial. Total and component costs were compared between treatment arms and across hospitals. Inpatient costs were higher in the HD-MTX and DEX arms when compared to the C-MTX and PRED arms at the end of therapy. There was no difference in cost between these arms at last follow-up. Considerable variation in total costs existed across centers to deliver the same therapy that was driven by differences in inpatient days and pharmacy costs. The more effective regimens were found to be more expensive during therapy but were ultimately cost-neutral in longer term follow-up. The variations in cost across centers suggest an opportunity to standardize resource utilization for patients receiving similar therapies, which could translate into reduced healthcare expenditures.

R-hyper-CVAD versus R-CHOP/cytarabine with high-dose therapy and autologous haematopoietic stem cell support in fit patients with mantle cell lymphoma: 20 years of single-center experience.

Standard of care for untreated mantle cell lymphoma (MCL) is still debated. At the University Hospital Zurich, advanced MCL in physically fit patients is treated either with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone induction followed by consolidating high-dose chemotherapy and autologous stem cell support (R-CHOP/HD-ASCT), or with rituximab plus fractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone alternating with high-dose methotrexate-cytarabine (R-hyper-CVAD/MTX-AraC) without consolidating HD-ASCT upon physicians' and patients' choice. We retrospectively analysed the outcome and therapy tolerance in patients with MCL treated with R-CHOP/HD-ASCT or R-hyper-CVAD/MTX-AraC at the University Hospital Zurich between January 1996 and January 2016. Forty-three patients were included; 29 patients received R-CHOP/HD-ASCT and 14 patients R-hyper-CVAD/MTX-AraC. Mean age at diagnosis was 54.4 years (range 38-68 years). Thirty-five patients (81.4%) completed the entire first-line therapy (n = 24 in the R-CHOP/HD-ASCT group, n = 11 in the R-hyper-CVAD group). Of those, all patients responded and 97% achieved a complete remission (CR). With a mean follow-up of 5.7 years 10-year progression-free survival (PFS) for all patients was 32% and overall survival (OS) was 76%, with no difference between the two therapy groups. Complication-induced hospitalisation rate, haematological toxicity and economic burden were significantly higher in the R-hyper-CVAD therapy group. In contrast, quality of life and global health state were better in the R-hyper-CVAD therapy group. Both first-line therapies showed similar outcome with a median OS longer than 10 years. Due to significantly lower haematological toxicity and lower economic burden, we recommend R-CHOP/HD-ASCT as first-line therapy in fit adult patients with advanced MCL.

Low-dose RATG with or without basiliximab in renal transplantation: a matched-cohort observational study.

BACKGROUND/AIMS: In renal transplantation, peri-operative low-dose rabbit-antithymocyte-globulin (RATG) plus basiliximab induction prevented acute allograft rejection more effectively than post-operative RATG plus basiliximab induction. We investigated the specific antirejection contribution of basiliximab in this context. METHODS: This single-center, observational, matched-cohort study evaluated allograft rejections (primary outcome), steroid exposure and side effects, GFR (iohexol plasma clearance) and treatment costs in 16 deceased-donor renal transplant recipients induced with RATG (0.5 mg/kg/day) and 32 age-, gender- and treatment-matched reference-patients given RATG plus basiliximab (20 mg on days 0 and 4). RESULTS: Induction was well tolerated. At 18 months, 8 patients (50%) vs. 3 reference-patients (9.4%) rejected the graft [HR (95% CI): 6.53 (1.73-24.70), p = 0.006]. Difference was significant (p < 0.01) even after adjusting for recipient/donor age and gender, cold ischemia time and HLA mismatches. There were 1 antibody-mediated rejection and 2 moderate cellular rejections in patients vs. none in reference-patients (p = 0.032). The median (interquartile range) prednisone cumulative dose was remarkably higher in patients than reference-patients [4.78 (1.12-6.10) vs. 0.19 (0.18-3.81) grams, p = 0.002]. Three patients vs. 24 reference-patients were off-steroid at study end (p < 0.001). Three patients vs. no reference-patient developed new-onset diabetes (p = 0.003). Both inductions similarly depleted B-cells. Outcomes of AZA- vs. MMF-treated participants were similar. GFR was similar in all groups. Compared to MMF, AZA therapy saved ≈ EUR 2,500/year and by month 14.3 post-transplant compensated basiliximab costs. CONCLUSION: In renal transplantation, basiliximab plus peri-operative low-dose RATG more efficiently prevented allograft rejection than RATG monotherapy, and minimized steroid exposure and toxicity. AZA- vs MMF-based maintenance immunosuppression largely compensated the extra costs of basiliximab.

Prognostic significance of geriatric assessment in combination with laboratory parameters in elderly patients with aggressive non-Hodgkin lymphoma.

The age-adjusted International Prognostic Index (IPI) is an important prognostic factor for patients with non-Hodgkin lymphoma (NHL). We investigated whether a geriatric assessment (GA) is of additional prognostic value in NHL. In this prospective cohort study of 44 patients aged 70 years or older with NHL receiving rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), a GA was administered before the start of chemotherapy. GA was composed of the Mini Nutritional Assessment (MNA), Groningen Frailty Indicator (GFI), Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), Mini Mental State Examination (MMSE) and levels of albumin, creatinine, lactate dehydrogenase (LDH) and hemoglobin. Multivariate analyses were performed using logistic regression and the Cox regression model. After adjustment for sex, age, comorbidity and univariate laboratory values with p ≤ 0.1, abnormal MNA and GFI scores and low hemoglobin level were associated with not being able to complete the intended chemotherapy: odds ratio (OR) 8.29 (95% confidence interval [CI]: 1.24-55.6; p = 0.03), 9.17 (95% CI: 1.51-55.8; p = 0.02) and 5.41 (95% CI: 0.99-29.8; p = 0.05), respectively. Adjusted for sex, age, comorbidity, age-adjusted IPI and univariate laboratory values with p ≤ 0.1, frailty by GFI and low hemoglobin were associated with worse survival, with a hazard ratio (HR) of mortality of 2.55 (95% CI: 1.07-6.10; p = 0.04) and 4.90 (95% CI: 1.76-13.7; p = 0.002), respectively. We conclude that (risk of) malnutrition, measured with the MNA, frailty, measured with the GFI, and low hemoglobin level had additional predictive value for early treatment withdrawal, and GFI and hemoglobin were, independent of the age-adjusted IPI, predictive for an increased mortality risk.

Pharmacoeconomic implications of lenalidomide maintenance therapy in multiple myeloma.

We compared the three arms of the MM-015 randomized phase III clinical trial [melphalan and prednisone (MP), MP plus lenalidomide (MPR), and MPR plus lenalidomide maintenance (MPR-R)] to determine whether the addition of lenalidomide maintenance therapy for primary treatment of multiple myeloma is cost-effective. We used progression-free survival and adverse event data from the MM-015 study for the analysis. Two novel measures of cost-effectiveness termed the Average Cumulative Cost per Patient (ACCP) and the Average Cumulative Cost per Progression-Free Survivor (ACCPFS) were developed for the purpose of this analysis. The ACCP of MP was USD 18,218, compared to USD 167,862 for MPR and USD 309,173 for MPR-R. The ACCPFS was highest with MPR at USD 1,555,443, while MP was USD 313,592 and MPR-R was USD 690,111. MPR-R is superior to MPR in terms of preventing the first progression after initial therapy. However, the addition of lenalidomide to MP in the induction and also in the maintenance setting leads to significant costs.