scholarly journals Characteristics of Environmental Exposure-Associated Versus Unexposed High-Grade B-Cell Lymphomas in Veterans: A Single Center, Matched Case-Control Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4488-4488
Author(s):  
Helen Ma ◽  
Yi Ouyang ◽  
Pankaj Gupta
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Causes Of Death ◽  
Patient Characteristics ◽  
High Grade ◽  
First Line ◽  
Unexposed Group ◽  
First Line Therapy ◽  
Younger Age ◽  
Age Of Diagnosis

Abstract Introduction: Environmental exposures, such as Agent Orange and other chemicals, are associated with the development of non-Hodgkin lymphomas (NHL). Military personnel and civilians in theaters of conflict are especially at high risk. The mechanism is still not well understood. We have initiated studies to examine the association of dioxin exposure, changes in DNA methylation, and the development of high-grade B-cell NHL. Methods: Patients diagnosed with high grade B-cell NHL were identified from the VA Long Beach medical record system for database abstraction and tissue analysis. Subjects with sufficient clinical data including diagnosis, date of diagnosis, age of diagnosis, exposure to toxins, treatments, date of last follow up, date of death, cause of death were included in the study. Patients were matched by exposure vs no exposure and international prognostic index (IPI), as well as duration in military and tour of duty when possible. Formalin-fixed paraffin-embedded specimens from a subset of these patients (where sufficient tissue was available for analysis) with and without known exposures were analyzed for differences in DNA methylation by enzymatic methyl sequencing. Descriptive statistics were used to summarize patient characteristics. Two sample t- and chi-square tests were used to compare the exposed and unexposed lymphoma groups. Overall survival was calculated from time of diagnosis to death from any cause and plotted on a Kaplan-Meier curve and compared using the Log rank test. The Fisher's exact test was used to compare the causes of death between the two groups using SAS 9. Results: Fifty-two patients were included in the study. Patient characteristics were well-balanced between the two groups. The duration of active duty, interval from military enlistment to diagnosis of NHL, and first-line therapy (generally anthracycline-based) were similar. There was a trend toward higher proportion of patients with advanced (stage III or IV) disease and younger age of diagnosis in patients with exposure-associated NHL (p=0.07). The median duration of response to first-line therapy (DOR1) trended towards being shorter (median, 0.8 years; range 0.03-25 years) in patients with exposure related NHL compared to median DOR1 of 2.7 (range, 0.02-25 years) in those without exposure, p=0.056. Median overall survival was 11.5 years in the exposure group and 10 years in the unexposed group, p=0.31. A higher portion of patients in the exposed group died from NHL compared to unexposed group (38% vs 15%), p=0.057. Other competing causes of death, which were more likely in the unexposed group, included other cancers, cardiac disease, infection, end stage kidney disease, dementia and unknown. Six exposed and six unexposed samples were sequenced with over 10,000 statistically significant differentially methylated regions (DMRs) out of 40,605 DMRs tested. Details of differences in methylation of specific genes and their potential pathophysiological and therapeutic implications will be discussed in the presentation. Conclusions: Patients with exposure-related high-grade B cell NHL who were matched by IPI with unexposed lymphomas did not differ significantly in baseline characteristics including time from enlistment to diagnosis and overall survival. In the exposure-related NHL group, certain findings trended toward significance, including younger age at diagnosis, higher proportion diagnosed at an advanced stage, shorter DOR1, and higher proportion died of NHL. This single center cohort, however, was small and heterogeneous. We are therefore currently expanding this study to examine a larger, multi-center cohort to confirm and extend our clinical and translational findings. Disclosures No relevant conflicts of interest to declare.

scholarly journals The first-line therapy of aggressive non-Hodgkin’s lymphomas in russian clinical practice: data from the EQUILIBRIUM study

2020 ◽  
Vol 15 (2) ◽  
pp. 10-18
Author(s):  
L. G. Babicheva ◽  
I. V. Poddubnaya
Keyword(s):  
Overall Survival ◽  
Clinical Practice ◽  
Complete Remission ◽  
B Cell ◽  
Long Term Results ◽  
First Line ◽  
Therapy Efficacy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Hodgkin's Lymphomas

The objective: evaluation of effectiveness of the first-line therapy with rituximab of B-cell lymphoproliferative diseases in Russian clinical practice in the period from 2014 to 2017.Materials and methods. The EQUILIBRIUM post-registration multicenter study included 1000 patients aged 21 to 91 years old with a verified diagnosis of B-cell non-Hodgkin’s lymphoma, or chronic lymphocytic leukemia, who received at least 4 cycles of rituximab-containing therapy with Acellbia®. The group of aggressive non-Hodgkin’s lymphomas (aNHL), which is the subject of this article, included 295 patients with a median age of 55.9 years: diffuse B-large cell lymphoma – 87 %, primary mediastinal lymphoma – 11 %, Burkitt’s lymphoma – 1 %. Group characterized by the presence of aggressive clinical signs reflecting the poor prognosis: in the majority of patients, generalized stages were diagnosed (61 %), in half of the cases (50.2 %), extranodal localization of tumor foci was detected (in 32.4 % of patients there were 2 or more). The overwhelming majority of patients (84.5 %) received adequate treatment complying with national and international recommendations (R-CHOP, R-CHOEP and R-EPOCH, high-intensity NHL-BFM-R, R-HyperCVAD and R-MACOP-B regimes). The use of R-CVP, FCR, RB, Chl-R, R-monotherapy treatment programs (which received 15.5 % of patients) was considered inadequate for this category of patients.Results. According to the results of the final assessment, high therapy efficacy was established: the overall response exceeded 90 %, complete remission was achieved in most patients with aNHL (68.5 %), partial remission – in every 5th patient (21.8 %). With a median follow-up of 15 months, 16 (5.42 %) deaths and 34 (11.53 %) events were registered. Median of event-free survival and overall survival have not been achieved. Statistically significant differences depending on first-line therapy efficacy were found in overall survival (p = 0.00000) and eventfree survival (p = 0.00000), once again confirming that the main goal of aNHL treatment is to achieve complete remission.Conclusion. Available and compliant with national clinical guidelines treatment of aNHL patients with Russian bioanalogue of anti-CD20 monoclonal antibodies (Acellbia®) demonstrates high immediate efficacy and acceptable long-term results, comparable to a retrospective analysis of previous clinical studies of the original drug rituximab.

Fludarabine Monophosphate as First Line Therapy for Chronic Lymphocytic Leukemia (CLL) - 11 Years Clinical Experience.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4970-4970
Author(s):  
J.E. Novoa ◽  
A.L. Rojo ◽  
B. Beñaran ◽  
R. Draper ◽  
H. Calvo ◽  
...  
Keyword(s):  
Overall Survival ◽  
Monoclonal Antibodies ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Response Rate ◽  
Lymphocytic Leukemia ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Intravenous Formulation

Abstract Background: fludarabine (F) has become the standard first line therapy for chronic lymphocytic leukemia (CLL) in younger patients. Treatment of early stage patients with chlorambucil without risk stratification has not been shown to prolong survival. In recent years effective and potentially curative approaches such as nucleosides analogues, stem cell transplantation or monoclonal antibodies have been developed. The attraction of monoclonal antibodies is based on selective targeting of tumor - relevant surface markers and a distinct mechanism of action (antibody-dependent cellular cytotoxicity). Aims: to assess the efficacy, safety and quality of life of F in previously untreated B-cell CLL patients in a group of medical institutions in Uruguay during 11 years (1995–2006). Methods: 168 patients between the period 1995 – 2006 were evaluated.120 of them received F intravenous formulation (1995–2006) and 48 the oral one (2002–2006). Age: 48 – 85 years old, media 67 years old. Gender: male 90, female 78. Inclusion criteria for B-cell CLL was Binet stages B, C and A progressive (Ap), 18 to 85 years old, non multiorganic failure, performance status 0 – 2 (WHO), written informed consent. First condition was non previous treatment. Staging: Binet A 12/168, B 116/168 & C 40/168. Treatment: as first line therapy all the patients received (minimum): 6 cycles of i.v. Fludarabine (Fludara®, Schering) 25 mg/m2/daily (5 days) e/30 days or Oral Fludarabine, 40 mg/m2/daily (5 days), 6 cycles. Results: on this B-cell CLL cohort the overall response rate (ORR) was 78% (CR+PR), 80% of them have immunophenotypic response. Safety: on the 1100 cycles in 168 patients, the toxicity was: 1 AIHA, 2 pancytopenia, 3 plaquetopenia. Grade 3–4 infection rate was 1,3%. No alopecia was observed in any patient. Kaposi sarcoma (0,7%). Mortality rate: 1,7% (3/168 patients). Other adverse factors to overall survival were, age over 65 (p=0,0001) and hepatic impairment (p=0,0001). Toxicity: (WHO>2): granulocytopenia 28%, thrombocytopenia 8%, infection 2%. Although fludarabine-treated patients experienced more significant myelosuppression, no difference in the treatment group was demonstrated. Causes of death: Richter 12%, sepsis 5%, associated disease 34%, second malignancy 17% and others 30%. Comparing oral with intravenous formulation in overall survival the results were: CLL 34% vs 36% (p= NS). Conclusions: fludarabine monofosfate (Fludara®) looks like an effective and safe treatment for B-cell CLL. The oral and intravenous formulations have a similar response rate in elderly and young patients. The challenge remains to integrate new information to apply novel therapies in a disease-specific and risk-adapted maner. A longer follow up and a larger trial, might be needed to confirm these results.

scholarly journals Clinical Characteristics and Treatment Outcomes in Patients Diagnosed with Primary Mediastinal Large B-Cell Lymphoma at Princess Margaret Cancer Centre from 1994-2012

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4447-4447
Author(s):  
Anna M. Dyszkiewicz-Korpanty ◽  
Manjula Maganti ◽  
David C. Hodgson ◽  
John G. Kuruvilla ◽  
Vishal Kukreti ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Patient Characteristics ◽  
Current Therapy ◽  
Second Line ◽  
First Line ◽  
Cancer Centre ◽  
Line Chemotherapy

Abstract Introduction: Primary mediastinal B-cell lymphoma (PMBCL) is a rare clinical entity representing less than 2-4% of Non-Hodgkin lymphomas. PMBCL typically occurs in young adults, more often in females, with early stage disease usually limited to the antero-superior mediastinum. PMBCL tends to have a more locally aggressive clinical course with a substantial percentage of patients with primary refractory disease or early relapse. Patients with primary refractory or relapsed disease have a lower probability response to second-line therapy and proceeding to autologous stem cell transplant (ASCT). The optimum chemotherapy regimen and role of radiation are currently the subject of debate; for this reason we evaluated our experience using a uniform treatment policy of combined modality therapy (CMT), including factors that influence patient outcomes. Methods: We analysed 88 patients (median age 35, range 15-64) diagnosed with PMBCL, treated at Princess Margaret Cancer Centre from 1994-2012. Data on stage, clinical prognostic factors, pathologic characteristics (including presence of sclerosis) treatment and outcome were retrieved from a prospective lymphoma database and pathology reports. Statistical analysis was performed to assess the overall survival (OS) and progression free survival (PFS) at 5 years; PFS events were progressive disease (PD), relapse or death from any cause. Patient characteristics are shown in Table 1 Results: All patients received treatment with curative intent. In the majority of patients first-line chemotherapy was cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP, 47 patients) or CHOP + rituximab (R-CHOP, 38 patients) (average number of cycles = 6); standard involved field consolidative radiation was given to 68/83 patients (82%), with a median dose of 35 Gy, usually in 20 fractions. Following the first line treatment, 38 patients achieved CR (complete response), 33 patients had PR (partial response), PD occurred in 18 patients, 10 patients with initial response relapsed. 28/88 patients with PD or relapse received second line chemotherapy (cisplatin-based or Mini-BEAM) and 6/28 went on to ASCT. Twenty one of 88 (24 %) patients died from progressive lymphoma, 2/88 died of other causes. Overall survival (OS) at five years was 72.4%, and five year PFS in was 67.7%. We observed significantly inferior five year-OS and PFS in men by univariate analysis (p=0.019; OS= 51.9% vs 80.2% in women and p=0.022; PFS= 47.6 % vs 75.2% in women, respectively); The presence of sclerosis on tumor biopsy also resulted in inferior OS and PFS (OS= 60.4% vs 89.3 %, p=0.0045; PFS= 56.1% vs 81.7%, p=0.013, respectively);PFS and OS in patients treated with R-CHOP was superior to patients who received chemotherapy without Rituximab( PFS of 84.2% vs 55.8%, p= 0.0099 and OS of 89.2% vs 61.9%, p= 0.012). In multivariate analysis, male gender and tumor pathology (PMBCL with sclerosis) were predictive of inferior OS (p=0.018 and p= 0.022, respectively) and also, inferior PFS (p= 0.0499 and p= 0.024, respectively); age at diagnosis, stage and bulk did not have independent impact on OS or PFS. Conclusions: Current therapy with R-CHOP and radiation result in excellent PFS and OS. The reasons for adverse outcomes in males in our cohort and pathological correlates of extensive sclerosis are being explored. Table 1. Patient characteristics at presentation (n=88) Variable N (%) Females 62(70.4) Stage I 39(44.3) Stage II 42(47.7) Stage III-IV 8(9.1) B symptoms 27(30.7) Elevated LDH 44(50) Bulk > 10 cm 60 (68.2) Extranodal disease 37 (42) Disclosures Kukreti: Celgene: Honoraria. Porwit:Beckman-Coulter: Speakers Bureau.

Double and Triple Hit Diffuse Large B Cell Lymphomas and First Line Therapy

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4885-4885
Author(s):  
Michael V. Jaglal ◽  
Deniz Peker ◽  
Jianguo Tao ◽  
Jennifer L. Cultrera
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Treatment Regimen ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
First Line ◽  
Cns Disease ◽  
Entire Cohort ◽  
First Line Therapy ◽  
Genetic Abnormalities

Abstract Abstract 4885 Background: B cell lymphoma, unclassifiable, with features intermediate between diffuse large B cell lymphoma (DLBCL) and Burkitt lymphoma (BL) or Burkitt like lymphoma is a high grade lymphoma, with a high proliferation index and a complex karyotype mostly involving MYC and BCL-2 genes, so called “double hit” as well as BCL-6 genes, so called “triple hit”. This high grade lymphoma shows an aggressive behavior for which the most appropriate therapeutic approach is not established. Methods: This was a single center retrospective review of patients with a confirmed diagnosis of B cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL from 2006 to 2012. The definitive diagnosis in all cases was based on morphological and phenotypic features, and genetic abnormalities involving MYC, BCL-2, and BCL-6. Clinicopathological data was extracted including age, gender, primary disease location, phenotypic subtype, genetic abnormalities by FISH, IPI scores, treatment regimens and survival data. Descriptive statistical analyses were utilized. Kaplan-Meier method was used to estimate OS and log rank test was used to compare the groups. All data were analyzed using SPSS version 19.0 statistical software. Results: 31 patients with “Double or Triple Hit” lymphomas were identified between 2006 and 2012. The age range at diagnosis was 33–87 years with median age of 71. 23 of 31 patients (74 %) were ≥ 60 years old. Male to female ratio was 1.58:1 (19:12). The median ECOG PS was 1. No patients had HIV. A majority of patients presented with extranodal disease 21 out of 31 patients and only 10 patients presented with nodal disease. The mean overall survival of the entire cohort was 28 months with ranges 3 to 40 months. 20 of 31 patients (65%) are currently alive. RCHOP was the most utilized treatment regimen in the cohort of alive patients 13 out of 20 patients (65%). Patients who presented with CNS disease had a worse prognosis when compared to the entire cohort with a mean overall survival of 13 months versus non CNS disease overall survival was 32 months (p=0.014). In patients treated with RCHOP for first line therapy the overall survival was 33 months versus 17 months for non RCHOP regimens first line (p=.048). The non RCHOP regimens included Hyper CVAD, ESHAP, and RICE. Conclusions: RCHOP was the most utilized treatment regimen in the cohort of alive patients. The treatment regimen with the best efficacy in this retrospective study was RCHOP in first line treatment of “Double or Triple Hit” lymphomas. CNS disease is associated with worse prognosis in patients with “Double or Triple Hit” lymphomas in this retrospective study. Disclosures: No relevant conflicts of interest to declare.

Non-Hodgkin’s Lymphoma Refractory to First Line Therapy: Incidence, Associated Clinical and Histological Factors, and Outcome among 503 Newly Diagnosed Patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1373-1373
Author(s):  
Angela Gueli ◽  
Daniele Caracciolo ◽  
Manuela Zanni ◽  
Luciana Bergui ◽  
Paolo Gavarotti ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cell ◽  
B Cell ◽  
Disease Progression ◽  
Refractory Disease ◽  
Advanced Stage ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Histological Factors

Abstract Introduction: Non-Hodgkin’s lymphoma (NHL) are malignancies usually sensitive to chemotherapy; this results in prolonged survival and often disease eradication in a large proportion of patients. Despite general improvements in treatment options, a variable number of NHL patients still shows refractoriness, i.e. poor or absent response to induction therapy. This study was undertaken to evaluate the actual rate of refractory patients, to identify possible factors predictive of refractory disease and to compare long-term outcome of refractory vs. responsive patients. Patients and Methods: Data have been collected on 503 NHL patients referred and treated at our Hematology Division between 1990 and 2005. The series included 461 B-cell and 42 T-cell NHL, main histologic subtypes included: 305 high-grade, 183 low-grade and 15 mantle-cell lymphoma. Patient median age was 53 yrs, 55% were male; 359 (73%) patients presented with advanced stage disease. Refractory patients were identified for stable/progressive disease or transient response with disease progression within 6 months, following first-line therapy. Overall, 298 (59%) patients received conventional chemo-radiotherapy, 205 (41%), with either high-risk presentation or unfavorable histology, had high-dose sequential therapy (HDS) with autograft front-line; rituximab was employed in 158 (31%) patients. Results: Overall, 126 (25%) patients were refractory (39% with no response at all, 61% with short-lasting response soon followed by disease progression). The rate of refractoriness was as high as 40% in the small T-cell NHL subgroup, while the overall incidence was 24% for B-cell NHL. There was no significant difference in the distribution of refractory patients among the histological subtypes of B-NHL, in other words none of the B-cell NHL subtypes was specifically associated with poorer response. Among several parameters evaluated for their potential predictive value, in multivariate logistic regression analysis, two factors only were associated with a higher risk of refractory disease: high serum level of lactate dehydrogenase (LDH) and stages IIB-IV, with an Odds Ratio (OR) of 3.52 and 3.75, respectively; the use of HDS program was associated with reduced risk of refractory disease (OR=0.30). Overall, refractory patients had a definitely short life expectancy, with a median survival of 21 months and a 14-yr survival projection of 10%, which is markedly worse compared to 88%, 76% and 65% survival projections at respectively 5, 10 and 15 yrs., of responsive patients, as shown in Figure 1. Conclusions. i. patients with refractory disease represent approximately one fourth of NHL undergoing induction therapy; ii. besides advanced stage and high LDH levels, no other clinical and histological factors are specifically associated to refractoriness; iii. further studies are needed to identify markers predictive of refractoriness, in order to design induction therapies adapted for refractory patients, given their dismal outcome with currently available treatment strategies. Figure 1. Overall survival of 126 refractory and 377 responsive NHL ptients Figure 1. Overall survival of 126 refractory and 377 responsive NHL ptients

scholarly journals 364 KRAS mutations in patients with nonsquamous non–small-cell lung cancer: prevalence and relationship with PD-L1 expression, tumor mutation burden and smoking status

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A391-A391
Author(s):  
Marina Chiara Garassino ◽  
Delvys Rodriguez-Abreu ◽  
Shirish M Gadgeel ◽  
Dariusz M Kowalski ◽  
Kazuo Kasahara ◽  
...  
Keyword(s):  
Smoking Status ◽  
Patient Characteristics ◽  
First Line ◽  
Link Type ◽  
First Line Therapy ◽  
Mutational Status ◽  
Mutation Burden ◽  
Platinum Based Chemotherapy ◽  
Former Smokers ◽  
Nonsquamous Nsclc

BackgroundPembrolizumab is a standard-of-care first-line treatment for advanced/metastatic NSCLC, either as monotherapy (for patients with PD-L1 tumor proportion score [TPS] ≥1%) or combined with platinum chemotherapy. An improved OS benefit has been demonstrated for both pembrolizumab monotherapy and pembrolizumab plus chemotherapy in patients with higher tumor PD-L1 expression, and for pembrolizumab monotherapy in patients with higher tissue tumor mutation burden (tTMB). Mutations in KRAS occur relatively frequently in patients with nonsquamous NSCLC but infrequently in those with squamous NSCLC; most mutations are in codon 12. Notably, the pembrolizumab OS treatment effect was not diminished in patients with KRAS G12C mutations in phase 3 studies evaluating pembrolizumab monotherapy and pembrolizumab in combination with chemotherapy.1 2 Herein we describe prevalence of KRAS mutations among patients with advanced nonsquamous NSCLC from two phase 3 clinical studies evaluating first-line pembrolizumab (KEYNOTE-042 and KEYNOTE-189) and the relationship of such mutations with select patient characteristics.MethodsKEYNOTE-042 (NCT02220894) evaluated pembrolizumab versus platinum-based chemotherapy for advanced PD-L1–positive NSCLC (any histology) without EGFR/ALK alterations. KEYNOTE-189 (NCT02578680) evaluated pembrolizumab plus platinum-based chemotherapy versus platinum-based chemotherapy alone for metastatic nonsquamous NSCLC without EGFR/ALK alterations irrespective of tumor PD-L1 expression. Whole-exome sequencing of tumor tissue and matched normal DNA (blood) was performed for patients with nonsquamous histology. PD-L1 TPS was evaluated using the PD-L1 IHC 22C3 pharmDx assay (Agilent Technologies, Carpinteria, CA, USA). Prevalence of KRAS mutations and their relationships with TMB, PD-L1 TPS, and smoking status were analyzed descriptively.Results590 patients with nonsquamous NSCLC were included in these analyses (KEYNOTE-042, n=301; KEYNOTE-189, n=289). Overall, 42.9% of patients had tTMB ≥175 mut/exome, 81.4% were current/former smokers and, 40.3%, 42.7%, and 16.9% had PD-L1 TPS ≥50%, 1–49% and <1% respectively. KRAS G12C, G12D, and G12V mutations occurred in 11.0%, 4.1%, and 5.4% of patients, respectively. Prevalence of KRAS mutations by patient characteristics is summarized in the table (table 1). KRAS G12C mutations occurred almost exclusively in current/former smokers. KRAS G12C was enriched in tumors with tTMB ≥175 mut/exome and tumors with PD-L1 TPS ≥50%. Prevalence was highest in tumors with both tTMB ≥175 mut/exome and PD-L1 TPS ≥50%.Abstract 364 Table 1KRAS Mutation PrevalenceConclusionsKRAS G12C mutations occurred with moderate frequency in patients with nonsquamous NSCLC, with most occurring in current/former smokers. KRAS G12C mutations occurred at higher frequency in patient subgroups defined by higher tTMB and PD-L1 TPS.AcknowledgementsMedical writing assistance was provided by Christabel Wilson, MSc, of ICON plc (North Wales, PA, USA), funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.Trial RegistrationKEYNOTE-042, ClinicalTrials.gov, NCT02220894; KEYNOTE-189, ClinicalTrials.gov, NCT02578680ReferencesGadgeel S, Rodriguez-Abreu D, Felip E, et al. KRAS mutational status and efficacy in KEYNOTE-189: pembrolizumab (pembro) plus chemotherapy (chemo) vs placebo plus chemo as first-line therapy for metastatic non-squamous NSCLC. Ann Oncol 2019;30(suppl 11):xi64-xi5.Herbst RS, Lopes G, Kowalski DM, et al. Association of KRAS mutational status with response to pembrolizumab monotherapy given as first-line therapy for PD-L1-positive advanced non-squamous NSCLC in KEYNOTE-042. Ann Oncol 2019;30(suppl 11):xi63-xi4.Ethics ApprovalFor both trials, the protocol and all amendments were approved by the appropriate ethics committee at each center, the study was conducted in accordance with the standards of Good Clinical Practice. Patients provided written informed consent before enrollment.

scholarly journals Efficiency of lenalidomide, bortezomib and prednisone (RVP) in patients with newly diagnosed multiple myeloma

2019 ◽  
Vol 14 (1) ◽  
pp. 14-19 ◽  
Author(s):  
K. A. Belousov ◽  
T. A. Mitina ◽  
Yu. Yu. Chuksina ◽  
A. K. Golenkov ◽  
E. V. Kataeva ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Objective Response ◽  
Hematological Toxicity ◽  
Efficacy And Safety ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

Objective: to study the efficacy and safety of the antitumor RVP program (lenalidomide, bortezomib, prednisone) as a first-line therapy in patients with multiple myeloma (MM). Materials and methods. A prospective study involved 39 patients with MM (15 women, 24 men), median age 61 years (30–76 years). All patients had Durie–Salmon stage III disease. According to the paraprotein isotype variant, 19 patients (48.7 %) had Gk myeloma, 8 (20.5 %) had Gλ, 4 (10.2 %) – Ak, 1 – Aλ, 1 – Dk, 1 – paraproteinemia Bens-Jones k and 1 – Bens-Jones λ, 2 – Dλ, and 2 patients – nonsecreting MM. The average level of plasma cells in the bone marrow was 31.7 % (0.8–80.0 %). In 14 (35.8 %) patients there were plasmacytomas of various localization (spine, cranial bones, clavicle, pleura). Nine (23.0 %) patients had renal failure, requiring the start of renal replacement therapy. The average Karnovsky index in the study group was 50 %. All patients received RVP therapy (lenalidomide 25 mg in 1–14 days, bortezomib 1.3 mg subcutaneously in 1, 4, 8, 11 days, prednisolone 60 mg/m2; the interval between courses was 42 days) as the first line therapy. Evaluation of therapy efficacy, characterized by overall survival, objective response rates (the number of complete, very good partial and partial remissions) was performed after 6 treatment courses. Results. The median follow-up was 15 months; the median of overall survival was not achieved. Objective antitumor response achieved in 29 (74.3 %) patients, including complete remissions in 3 (7.6 %), very good partial remissions – in 7 (17.9 %), partial remissions – in 19 (48.7 %) patients. In 2 out of 9 patients who received renal replacement therapy, independence from dialysis therapy was achieved. Cases of III–IV stage hematological and non-hematological toxicity in the study were not noted. Conclusion. The antitumor RVP program showed high efficacy and safety as a first-line therapy in a non-selective group of patients, including those with a complicated MM course.

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