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1.
Soham D. Puvvada José Guillen-Rodriguez Abhijeet Kumar Lora Inclán Kara Heard Xavier I. Rivera Faiz Anwer Jonathan H. Schatz Daruka Mahadevan Daniel O. Persky 《Clinical Lymphoma, Myeloma & Leukemia》2018,18(1):58-64
Background
Mantle-cell lymphoma (MCL) and indolent non-Hodgkin lymphoma (iNHL) are incurable heterogeneous diseases characterized by relapse. There is a need for newer treatments in MCL and iNHL, especially in the relapsed/refractory (R/R) setting. We therefore investigated the novel combination of bortezomib (Velcade), cladribine, and rituximab (VCR) in front-line and R/R settings in MCL and iNHL (NCT00980395).Patients and Methods
Eligible patients included adults with biopsy-proven CD20-positive MCL and iNHL who met the criteria for treatment. Rituximab 375 mg/m2 intravenous (IV) day 1, cladribine 4 mg/m2 IV days 1 to 5, and bortezomib 1.3 mg/m2 IV days 1 and 4 were administered every 28 days for 6 cycles.Results
Twenty-four patients were enrolled onto the study with a median follow-up of 38.5 months. Median age was 66.5 years, and 46% had MCL. The most common adverse events were hematologic, with febrile neutropenia in 3 patients. Neuropathy was noted in 17% of patients, of which 8% was grade 3 or above. The overall response rate was 92%. For the entire cohort, and for MCL patients, the median progression-free survival and the median overall survival were not reached. The 2-year progression-free survival was 82% for the MCL group and 54% for the iNHL group; it was 80% for treatment-naive patients and 57% for R/R patients.Conclusion
VCR is effective in MCL and iNHL. Although hematologic toxicity can be an issue, this study demonstrates a high response rate to a novel combination and provides an alternative option in transplant-ineligible R/R MCL and iNHL. 相似文献2.
Sigal Grisariu Michael Y. Shapira Reuven Or Batia Avni 《Clinical Lymphoma, Myeloma & Leukemia》2018,18(4):272-279
Background
High-dose chemotherapy and autologous stem cell transplantation (ASCT) is the current standard of care for relapsed non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL). Conditioning regimens with high-dose carmustine have been associated with idiopathic pneumonitis syndrome. We, therefore, created a modified alternative TECAM conditioning regimen, consisting of etoposide, thiotepa, cytarabine, cyclophosphamide, and melphalan.Patients and Methods
We retrospectively analyzed our cohort of 212 NHL and HL patients, who had undergone ASCT with the TECAM conditioning regimen from 2000 to 2013. Although toxicity and engraftment were analyzed for all 212 patients, the survival analysis was performed for the 2 largest groups of patients, those with diffuse large B-cell lymphoma (DLBCL) and those with HL (n = 127) to minimize heterogeneity.Results
The 3-year overall survival among the DLBCL and HL patients was 0.618 (95% confidence interval [CI], 0.490-0.722) and 0.828 (95% CI, 0.701-0.904), respectively. Stage IV disease at transplantation was a statistically significant poor prognostic factor. Higher Eastern Cooperative Oncology Group performance status and progressive disease at transplantation were found to be borderline significant. No idiopathic pneumonitis syndrome cases were reported in our cohort. Six patients died of treatment-related toxicity during the first 100 days. The 3-year progression-free survival was 0.5 (95% CI, 0.37-0.61) for HL patients and 0.49 (95% CI, 0.36-0.60) for DLBCL patients.Conclusion
Our results are encouraging and justify evaluation of TECAM versus BEAM (carmustine, etoposide, cytarabine, melphalan) in a prospective multicenter study in a large homogenous patient population. 相似文献3.
Qingxiu Dang Hong Zhou Juan Qian Li Yang Jianfei Huang Yaping Zhang Wenyu Shi 《Clinical Lymphoma, Myeloma & Leukemia》2018,18(11):749-754
Introduction
Lysosomal-associated membrane protein 1 (LAMP1) is a lysosomal and plasma membrane protein that contributes to tumor metastatic potential and differentiation.Patients and Methods
We performed immunohistochemical staining to investigate LAMP1 protein expression levels in 122 diffuse large B-cell lymphoma (DLBCL) tumor samples and 45 reactive hyperplasia tissues. Correlations between LAMP1 expression, various clinicopathologic features, and patient prognosis were evaluated by univariate and multivariate analyses.Results
LAMP1 expression was greater in the DLBCL tissues than in the reactive hyperplasia tissues. High LAMP1 expression was significantly associated with a high international prognostic index (score, 3-5; P = .023) and elevated lactate dehydrogenase level (P = .028). Moreover, high LAMP1 expression (P = .026), elevated serum lactate dehydrogenase level (P = .011), and high international prognostic index (P < .001) were independently associated with worse overall survival and progression-free survival.Conclusion
These data provide the first evidence that LAMP1 expression is associated with a poor prognosis in patients with DLBCL. 相似文献4.
Characterizing Autoimmune Disease-associated Diffuse Large B-cell Lymphoma in a SEER–Medicare Cohort
Jean L. Koff Ashish Rai Christopher R. Flowers 《Clinical Lymphoma, Myeloma & Leukemia》2018,18(2):e115-e121
Background
Severe immune dysregulation such as seen in autoimmune (AI) disease is known to act as a significant risk factor for diffuse large B-cell lymphoma (DLBCL). However, little is known about the demographics or clinical outcomes of DLBCL that arises in the setting of AI disease.Patients and Methods
We used the Surveillance, Epidemiology, and End Results (SEER) database for patients with a diagnosis from 1999 to 2009 linked to their Medicare claims data through 2011 to characterize the presentation, treatment, and survival patterns in DLBCL patients, including those with rheumatoid arthritis, systemic lupus erythematosus (SLE), Sjögren syndrome, and other B-cell–mediated AI diseases. We examined the baseline clinical characteristics for patients with B-cell–mediated AI disease, plotted the overall survival and lymphoma-related survival (LRS) for these groups, and compared the median survival times.Results
Patients with DLBCL and AI disease were more commonly female. However, patients with DLBCL and rheumatoid arthritis, SLE, Sjögren syndrome, or other B-cell AI diseases did not differ from other DLBCL patients in any other baseline presenting features and received similar first-line treatment. A trend toward decreased LRS was seen in patients with SLE and DLBCL compared with all other groups, but this difference was not statistically significant in this cohort.Conclusion
In the present retrospective claims-based cohort of older patients with DLBCL, concomitant AI disease was uncommon and was more likely to occur in female DLBCL patients, which likely reflects the greater incidence of AI disease in women. The possibility of lower LRS for SLE patients should be explored in future studies. 相似文献5.
Stephen D. Smith Shruti Gandhy Ajay K. Gopal Prathima Reddy Mazyar Shadman Brian G. Till Ryan C. Lynch Sandra Kanan Andrew Cowan Lauren Low Brian T. Hill 《Clinical Lymphoma, Myeloma & Leukemia》2019,19(1):48-52
Background
Initial treatment of mantle cell lymphoma (MCL) incorporating autologous stem cell transplantation affords long-term remissions, but relapses still occur. Optimal pretransplant therapy will afford high complete response rates and not impair stem cell collection. Incorporation of bortezomib represents a natural evolution of pretransplant therapy, given its proven first-line efficacy and minimal impact on stem cell collection.Patients and Methods
At the University of Washington/Seattle Cancer Care Alliance and the Cleveland Clinic Foundation, we developed modified VR-CAP/R+ara-C (bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone, alternating with rituximab and high-dose cytarabine), for transplant-eligible patients with MCL. This regimen was administered as standard-of-care, pretransplant therapy to consecutive patients with MCL from April 2015 to the present.Results
A total of 37 patients were treated with this regimen, including 18 at the University of Washington/Seattle Cancer Care Alliance and 19 at the Cleveland Clinic Foundation. Most patients had intermediate- or high-risk disease by both (mantle-cell lymphoma international prognostic index (MIPI)-B and MIPI-C category. Complete response to induction was achieved in 32 (86%) of 37 evaluable patients; 2 achieved partial response, and 3 had primary refractory disease. Stem cell collection was successful in 1 attempt in 30 of 32 patients. The median follow-up of survivors measured from start of treatment is 17.4 months. Five patients have progressed, and 4 have died (2 owing to lymphoma, 2 from toxicity).Conclusion
Modified VR-CAP/R+ara-C is feasible pretransplant therapy for patients with MCL and is associated with a high rate of complete response and eligibility for autologous stem cell transplantation. 相似文献6.
Rustain Morgan Mark Perry Jennifer Kwak Alexandria Jensen Manali Kamdar 《Clinical Lymphoma, Myeloma & Leukemia》2018,18(11):731-736
Introduction
Mantle cell lymphoma (MCL) is a rare subtype of non–Hodgkin lymphoma and requires both bone marrow biopsy and fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) to correctly stage the disease at diagnosis. However, accurate identification of bone marrow involvement by lymphoma on FDG PET/CT scans has not been previously demonstrated. We hypothesized that a voxel-based analysis of the iliac bones on the FDG PET/CT scan might provide insight into bone marrow involvement.Patients and Methods
A retrospective cohort study of patients with a diagnosis of MCL who had undergone both single iliac bone marrow biopsy and FDG-PET/CT scan from 1 study site were included in the development phase (n = 10). An additional 12 patients from a second institution were included in the validation phase. Using a semiautomated workflow, a voxel-based data set of FDG uptake within the bilateral iliac bones was captured for each patient. In the development phase, empirical receiver operating characteristic curves for each data set were fit. We then identified the standardized uptake value (SUV) threshold cutpoints at which the sensitivity and specificity were optimized to 100%. In the validation phase, we evaluated the performance of these candidate SUV threshold cutpoints in 15 additional patients from a second institution.Results
We found that 1 cutpoint, > 38% of voxels with activity < 0.95, outperformed all the other candidate cutpoints, correctly classifying all patients except for 1 (overall sensitivity, 100%; specificity, 87.5%).Conclusion
The ability to correctly identify bone marrow involvement using FDG PET/CT-based voxel analysis provides promise as a novel noninvasive method of accurate staging. 相似文献7.
John M. Burke Andrei Shustov James Essell Dipti Patel-Donnelly Jay Yang Robert Chen Wei Ye Wen Shi Sarit Assouline Jeff Sharman 《Clinical Lymphoma, Myeloma & Leukemia》2018,18(8):e327-e331
Background
Entospletinib (GS-9973) is an oral, selective inhibitor of spleen tyrosine kinase. Entospletinib monotherapy was evaluated in a multicenter, phase II study of subjects with relapsed or refractory B-cell malignancy.Patients and Methods
The study included 43 patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The participants received 800 mg of the original, monomesylate formulation of entospletinib twice daily as a starting dose; the doses could be reduced because of toxicity throughout the study.Results
No patient achieved a complete or partial response, 5 patients (12%) had stable disease, and 26 patients (60%) had progressive disease. Progression-free survival (PFS) at 16 weeks was 3.6% (95% confidence interval [CI], 0.3%-15.3%), and the median PFS was 1.5 months (95% CI, 1-1.7 months). The independent review committee–assessed nodal response for 27 evaluable patients showed a reduced tumor burden in 6 patients (22%). The median duration of entospletinib treatment for these 6 patients was 9 weeks (range, 3-24 weeks). One patient (4%) had a decrease of ≥ 50% in the sum of the product of the nodal diameters. The treatment-emergent adverse events occurring in ≥ 20% of the cohort were fatigue, nausea, decreased appetite, constipation, dyspnea, diarrhea, dehydration, cough, insomnia, and peripheral edema. The common laboratory abnormalities occurring in ≥ 20% of the subjects were lymphocytopenia, anemia, creatinine (chronic kidney disease), increased aspartate aminotransferase, hypoalbuminemia, total bilirubin, hyponatremia, leukopenia, increased alanine aminotransferase, increased alkaline phosphatase, and hyperglycemia.Conclusion
Entospletinib monotherapy at 800 mg twice daily demonstrated limited activity in patients with advanced, relapsed DLBCL. 相似文献8.
Paolo Strati Nathan Fowler Sergio Pina-Oviedo L. Jeffrey Medeiros Michael J. Overman Jorge E. Romaguera Loretta Nastoupil Michael Wang Fredrick B. Hagemeister Alma Rodriguez Yasuhiro Oki Jason Westin Francesco Turturro Sattva S. Neelapu Luis Fayad 《Clinical Lymphoma, Myeloma & Leukemia》2018,18(1):e103-e108
Background
The optimal management of patients with follicular lymphoma Grade 3 (FLG3) is controversial.Patients and Methods
This is a case series of 45 patients with FLG3 treated with first-line R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and observed for an extended time interval.Results
The overall response rate was 100% and the median progression-free survival (PFS) has not been reached, with a 3-year PFS of 70%; 14 (31%) patients relapsed, nearly all within 3 years. The baseline characteristic more strongly associated with a shorter PFS were lymph >4 node sites and presence of B symptoms. Three patients later progressed to diffuse large B cell lymphoma, all had baseline elevated serum lactate dehydrogenase level and high International Prognostic Index score. Median overall survival has not been reached. All 4 patients who later developed acute myeloid leukemia were older than 60 years at the time of start of therapy.Conclusion
R-CHOP is an effective first-line treatment for patients with FLG3, and might provide extended PFS, comparable with outcomes observed in diffuse large B-cell lymphoma, particularly in subgroups with limited nodal disease. 相似文献9.
Brendan G. Coutu Christopher T. Wilke Jianling Yuan Qing Cao Matthew R. Vernon Chung Lee Veronika Bachanova Kathryn E. Dusenbery 《Clinical Lymphoma, Myeloma & Leukemia》2018,18(1):65-73
Introduction
We evaluated the role of consolidative radiotherapy (RT) for patients undergoing high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) for relapsed or refractory diffuse large B-cell lymphoma (DLBCL).Materials and Methods
We reviewed the medical records of 72 consecutive patients who had undergone ASCT for relapsed or refractory DLBCL at our institution from 2006 to 2014. Pretransplant conditioning consisted of HDC and total body irradiation. Of the 72 patients, 13 received post-transplant consolidative RT at the discretion of the consulted radiation oncologist.Results
Consolidative RT was associated with significantly improved 2-year locoregional control (LRC) (92% vs. 68%; P = .04). However, no difference was seen in either the 2-year progression-free survival (PFS) (69% vs. 54%; P = .25) or overall survival (OS) (85% vs. 59%; P = .44). Analysis of the subgroup of 19 patients with persistent residual masses ≥ 2 cm on post-transplant imaging demonstrated a significant improvement in LRC (100% vs. 36%; P < .01), PFS (88% vs. 27%; P = .01), and OS (100% vs. 45%; P = .02) with consolidative RT.Conclusion
The use of consolidative RT after HDC and ASCT for relapsed or refractory DLBCL appears to significantly improve LRC. For patients with masses ≥ 2 cm after ASCT, improved 2-year PFS and OS were seen. Prospective trials are needed to further identify the patients who would derive the most benefit from consolidative RT in the ASCT setting. 相似文献10.
Francesco Gaudio Pasquale Pedote Artor Niccoli Asabella Tommasina Perrone Filomena Emanuela Laddaga Paola Sindaco Antonia Cimmino Dario D&#x;Abbicco Angela Pezzolla Giuseppe Rubini Giorgina Specchia 《Clinical Lymphoma, Myeloma & Leukemia》2018,18(6):e261-e266
Purpose
To identify the characteristics and outcomes of patients with extralymphatic Hodgkin lymphoma.Patients and Methods
We performed a retrospective single-institution study of 341 cases comprising 207 male (61%) and 134 female (39%) subjects with a median follow-up of 44 months.Results
Fifty-five patients (16%) had extralymphatic disease. The sites were lung in 29 patients (44%), bone in 22 (33%), liver in 12 (18%), and kidney in 3 (5%). In 46 patients (86%) only one organ was involved, while in 7 patients (13%) extralymphatic disease was present in 2 sites and in 2 patients (3%) in 3 sites. The extralymphatic disease group had a poorer prognosis than the lymphatic disease group. Complete remission rates in the extralymphatic and lymphatic patient subsets were 65% and 82% (P = .043), respectively.Conclusion
Extralymphatic disease in patients with Hodgkin lymphoma is a rare occurrence (16%) associated with poor clinical outcome. 相似文献11.
Vincent L. Hansen Morton Coleman Stephanie Elkins Jeffrey P. Letzer Moshe Yair Levy Lasika Seneviratne Jessica Rine Marina White Emil T. Kuriakose 《Clinical Lymphoma, Myeloma & Leukemia》2018,18(6):400-407.e1
Background
Panobinostat was recently approved by the US Food and Drug Administration and European Commission in combination with bortezomib and dexamethasone for patients with multiple myeloma who have received ≥ 2 regimens, including bortezomib and an immunomodulatory drug. The PANEX (panobinostat expansion) treatment protocol provided access to panobinostat and gathered additional safety data before commercial availability.Patients and Methods
In treatment phase 1, patients received panobinostat 20 mg 3 times per week plus bortezomib 1.3 mg/m2 twice weekly with dexamethasone 20 mg on the days of and after bortezomib treatment. Patients with no change or better in treatment phase 1 proceeded to treatment phase 2, when bortezomib was reduced to once weekly. Unlike in the phase III trial, PANORAMA-1 (panobinostat or placebo with bortezomib and dexamethasone in patients with relapsed multiple myeloma), bortezomib could be administered either subcutaneously or intravenously.Results
Thirty-nine patients with a median number of previous treatments of 4 (range, 1-12) were enrolled; most received subcutaneous bortezomib (87%). The overall response rate (partial response or better) was 56%. Grade 3/4 adverse events included thrombocytopenia (47%), fatigue (31%), dehydration (26%), and diarrhea (18%). Among the patients who received subcutaneous bortezomib, relatively low rates of peripheral neuropathy (all grade, 15%) and notable grade 3/4 adverse events (thrombocytopenia, 47%; diarrhea, 12%) were observed.Conclusion
Overall, data from the PANEX trial support regulatory approval of panobinostat plus bortezomib and dexamethasone and suggest the potential tolerability benefits of subcutaneous bortezomib in this regimen. 相似文献12.
H. Hasegawa M. Ando Y. Yatabe S. Mitani K. Honda T. Masuishi Y. Narita H. Taniguchi S. Kadowaki T. Ura K. Muro 《Clinical oncology (Royal College of Radiologists (Great Britain))》2018,30(10):667-673
Aims
Although platinum-based combination chemotherapies are commonly used for unfavourable subsets of cancer of unknown primary (CUP), the prognosis remains poor. Several studies have suggested that gene expression profiling or immunohistochemistry was useful for the prediction of primary sites in CUP, and site-specific therapy based on predicted primary sites might improve overall outcomes. In Japan, to identify primary sites, immunohistochemical tests were commonly used for CUP in clinical practice. However, it is unclear whether site-specific therapy based on predicted primary sites by pathological examination contributes survival benefit for unfavourable CUP subsets.Patients and methods
In this study, 122 patients with unfavourable subsets of CUP were retrospectively reviewed. Ninety patients assigned to cohort A after July 2012 had received chemotherapy according to predicted primary sites; 32 patients assigned to cohort B before June 2012 had received platinum-based empiric chemotherapy.Results
In cohort A, 56 patients (62.2%) with predicted primary sites by pathological examination received site-specific therapy; 34 patients (37.8%) with unpredictable primary sites received platinum-based empiric chemotherapy, the same as cohort B. The median overall survival was 20.3 months in patients with predictable primary sites in cohort A and 10.7 months in those of cohort B, with a significant difference between these cohorts (P = 0.03, adjusted hazard ratio = 0.57, 95% confidence interval 0.34–0.94).Conclusion
Site-specific therapy based on predicted primary sites by pathological examination could improve prognosis in patients with an unfavourable subset of CUP. 相似文献13.
Øystein Fluge Bård Mannsåker Anders Torp Ingvil Mjaaland Lars Helgeland Jan Klos Olav Mella Sigbjørn Berentsen Peter Meyer 《Clinical Lymphoma, Myeloma & Leukemia》2018,18(2):125-135.e3
Background
The role of consolidative radiotherapy (RT) in advanced diffuse large B-cell lymphoma (DLBCL) is not established.Patients and Methods
In a population-based retrospective analysis of patients with DLBCL in Western Norway during 2003 to 2008, 170 consecutive patients admitted to Haukeland University Hospital (HUS) and 94 to Stavanger University Hospital (SUS) were included. The mean age was 64 years (range, 17-95 years), 147 patients (56%) were male, 80 patients (30%) had stage I/II, 126 patients (48%) stage III/IV, and 57 patients (22%) had primary extranodal disease.Results
There were no differences between hospitals in patient characteristics, use of rituximab, number of chemotherapy courses or cumulative doses, or in distribution of response categories after chemotherapy. The use of RT was significantly different: 17 patients (23%) received RT at SUS and 92 patients (65%) at HUS (P < .001). For 219 patients with International Prognostic Index (IPI) score of 0 to 3, 5-year cancer-specific survival (CSS) was 67% at SUS and 81% at HUS (P = .012). For 73 patients with complete response after chemotherapy there were no differences in survival between patients with and without RT. For 138 patients with any residual mass after chemotherapy, there were highly significant differences in favor of receiving RT (n = 81) versus no RT (n = 57): 5-year CSS 89% versus 69% (P < .001), and 5-year overall survival 82% versus 59% (P = .005). The effect of RT on residual mass was evident in most subgroups, mainly in low to intermediate risk, but not in high-risk (IPI 4-5) patients.Conclusion
With the limitations of a retrospective study, these data suggest that consolidative RT might improve survival in DLBCL patients with a residual mass after chemotherapy, also in advanced disease. 相似文献14.
Aleš Obr Vít Procházka Andrea Jirkuvová Helena Urbánková Eva Kriegova Petra Schneiderová Michaela Vatolíková Tomáš Papajík 《Clinical Lymphoma, Myeloma & Leukemia》2018,18(11):762-768
Background
TP53 mutation (TP53mut) and a complex karyotype (CK) were shown to be predictors of poor outcome in mantle-cell lymphoma (MCL). In this study we examined the combined effect of both of these risk factors.Patients and Methods
Patients diagnosed with MCL between January 2000 and December 2014 (n = 74) were evaluated. Forty-eight of them had available material for TP53 and cytogenetic examination. We analyzed the prognostic effect of combined TP53mut and CK in the cohort of patients treated with rituximab-containing therapy.Results
Three-year (3-y) overall survival (OS) and 3-y progression-free survival (PFS) in CK patients were shorter compared with non-CK (P = .001 for OS; P = .02 for PFS). TP53mut was a predictor of shorter survival compared with TP53 wild type (OS and PFS; P < .001). The incidence of TP53mut was not significantly associated with CK (P = .240). CK and TP53mut were predictors of inferior PFS and OS independent of age and Mantle-Cell Lymphoma International Prognostic Index, with hazard ratios of 2.35 (P = .024), 4.50 (P < .001) for PFS and 4.31 (P < .001), 5.46 (P < .001) for OS analysis in the CK and TP53mut groups, respectively. The combination of TP53mut and CK status stratified the patients into 3 prognostic groups (P < .001) with the worst outcome in patients with CK and TP53mut.Conclusion
TP53 mutation and CK occurred independently and patients harboring both had a dismal prognosis. The study suggests the importance of molecular cytogenetics and examination of the TP53mut status to be performed simultaneously before treatment. 相似文献15.
Hawk Kim SooHyun Kim Hyeoung-Joon Kim Yeo-Kyeoung Kim Jae-Yong Kwak Ho-Young Yhim Sung-Hyun Kim Young Rok Do Sukjoong Oh Sung-Eun Lee Saengsuree Jootar Jiu Wei Cui Dong-Wook Kim 《Clinical Lymphoma, Myeloma & Leukemia》2018,18(10):e391-e399
Introduction
BCR-ABL1 mutations require consideration during second-line tyrosine kinase inhibitor selection for patients with chronic myeloid leukemia (CML). The present retrospective analysis compared the frequency of BCR-ABL1 mutations in Asian and white patients in whom imatinib therapy had failed.Patients and Methods
A nonstudy cohort (76 Asian patients from community clinical practices) and 2 study cohorts (29 Asian and 352 white patients from dasatinib phase II and III clinical trials) were identified.Results
In the nonstudy cohort, 80 mutations were identified; the most frequent was T315I (15%), followed by phosphate-binding loop mutations E255K (11%), G250E (10%), and Y253H (10%). Asian patients had a greater proportion of T315I and phosphate-binding loop mutations compared with the white patients. The nonstudy cohort was less likely to have multiple mutations compared with either study cohort. Single mutations highly resistant to dasatinib, nilotinib, and bosutinib were more frequent in the Asian than in the white cohorts.Conclusion
These results suggest that mutational analysis findings will be invaluable for choosing an appropriate second-line tyrosine kinase inhibitor in Asia. 相似文献16.
Leslie Padrnos Brenda Ernst Amylou C. Dueck Heidi E. Kosiorek Brenda F. Ginos Angela Toro Patrick B. Johnston Thomas M. Habermann Jose F. Leis Joseph R. Mikhael Grzegorz S. Nowakowski Joseph Colgan Luis Porrata Stephen M. Ansell Thomas E. Witzig Craig Reeder 《Clinical Lymphoma, Myeloma & Leukemia》2018,18(10):664-672.e2
Background
Treatment outcomes have improved in lymphoid malignancies but relapse remains inevitable for most patients. Everolimus and lenalidomide have shown clinical activity as single agents in patients with relapsed and refractory Hodgkin and non-Hodgkin lymphomas.Patients and Methods
The present phase I/II trial for patients with relapsed and refractory lymphoid malignancy opened at Mayo Clinic from January 2011 to May 2013. The trial used a standard cohort 3 + 3 design to determine the maximum tolerated dose for the combination. Stem cell transplantation had failed in 27 of the patients (49%), 63% had stage IV disease, and ≥ 3 previous therapies had failed in 78%.Results
Of the 58 patients, enrolled, 55 were evaluable for analysis. The maximum tolerated dose was 5 mg/d for everolimus plus 10 mg/d for 21 days for lenalidomide. The most common grade ≥ 3 toxicities were hematologic and included neutropenia (56%), leukopenia (38%), and thrombocytopenia (33%). Seven patients discontinued the study because of adverse events. One patient died of disease progression. The overall response rate was 27% (15 of 55), with 38% (21 of 55) having stable disease.Conclusion
The present phase I/II trial of everolimus and lenalidomide for R/R lymphoma has shown the combination to be tolerable, with neutropenia as the main dose-limiting toxicity. Encouraging responses were seen in this heavily pretreated group, and the patients with a response had meaningful duration of response. 相似文献17.
18.
Rachel J. David Andrea Baran Kah Poh Loh Carla Casulo Paul M. Barr Jonathan W. Friedberg Patrick M. Reagan 《Clinical Lymphoma, Myeloma & Leukemia》2018,18(12):781-787
Introduction
Certain aggressive non-Hodgkin lymphoma subtypes are increasingly being treated with infusional DA-EPOCH-R (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab), which requires a central venous catheter. This study aims to identify the rates and predictors of line-associated complications (LACs) associated with DA-EPOCH-R therapy in NHL.Patients and Methods
We retrospectively identified all patients treated with DA-EPOCH-R at our institution between March 2011 and July 2016. We also identified a concurrent cohort of patients with diffuse large B-cell lymphoma treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone).Results
Forty-three patients received DA-EPOCH-R during the study period; 17 (39.5%; 95% confidence interval, 0.25-0.56) patients experienced at least 1 LAC (including venous thromboembolism, chemotherapy extravasation, and line-associated infection). Forty-four patients received R-CHOP during the study period; 8 (18.2%; 95% confidence interval, 0.08-0.32) patients experienced at least 1 complication. Compared with the R-CHOP cohort, patients treated with DA-EPOCH-R experienced a significantly higher rate of these complications (P = .03). In the DA-EPOCH-R cohort, grade 3 toxicity was seen in 41% (7/17). In univariate analysis, body mass index ≥ 35 kg/m2 and using a peripherally inserted central catheter line were significantly associated with an increased risk of venous thromboembolism (P = .04 and P = .02, respectively).Conclusions
Forty percent of patients receiving DA-EPOCH-R therapy developed LACs, almost one-half of whom experienced grade 3 toxicities. The complication rate was significantly greater in patients undergoing therapy with DA-EPOCH-R compared with those undergoing R-CHOP therapy. Clinicians need to balance these risks when selecting therapy. Future studies are needed to evaluate prophylactic anticoagulation strategies in this population. 相似文献19.
Susan O&#x;Brien Peter Hillmen Steven Coutre Paul M. Barr Graeme Fraser Alessandra Tedeschi Jan A. Burger Marie-Sarah Dilhuydy Georg Hess Carol Moreno Paula Cramer Emily Liu Stephen Chang Jessica Vermeulen Lori Styles Angela Howes Danelle F. James Kalpesh Patel Rudolph Valentino 《Clinical Lymphoma, Myeloma & Leukemia》2018,18(10):648-657.e15
Background
Multiple studies have demonstrated the efficacy and safety of ibrutinib for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and mantle cell lymphoma (MCL). This first-in-class inhibitor of Bruton's tyrosine kinase has become a standard treatment for patients with CLL and MCL.Patients and Methods
We conducted an integrated safety analysis to characterize the frequency, severity, natural history, and outcomes of adverse events (AEs) with ibrutinib versus comparators. Data were pooled from 4 completed randomized controlled studies that had included 756 ibrutinib-treated and 749 comparator-treated patients with CLL/SLL or relapsed/refractory MCL. Safety analyses included reporting of AEs using crude and exposure-adjusted incidence rates.Results
The median treatment duration was 13.3 months (maximum, 28.2 months) for ibrutinib and 5.8 months (maximum, 27.3 months) for comparators. When adjusted for exposure, diarrhea, atrial fibrillation, and hypertension were the only common grade ≥ 3 AEs more often reported with ibrutinib than with the comparators. Dose reductions (7% vs. 14%) and discontinuation (12% vs. 16%) because of AEs occurred less often with ibrutinib, and deaths due to AEs occurred at similar rates (6% vs. 7%). When adjusted for exposure, the corresponding data were all lower with ibrutinib than with the comparators (0.06 vs. 0.22, 0.11 vs. 0.22, and 0.06 vs. 0.09 patient-exposure-years, respectively). The prevalence of common grade 3/4 AEs with ibrutinib generally decreased over time, with the exception of hypertension.Conclusion
These results from an integrated analysis support a favorable benefit/risk profile of ibrutinib in patients with CLL/SLL and MCL. 相似文献20.