Prognostic value of blood levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in advanced non-small cell lung cancer (NSCLC) patients

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7196-7196
Author(s):  
V. Alberola ◽  
C. Camps ◽  
R. Sirera ◽  
L. Llobat ◽  
A. Blasco ◽  
...  
Keyword(s):  
Growth Factor ◽  
Plasma Levels ◽  
Advanced Nsclc ◽  
Performance Status ◽  
Prognostic Significance ◽  
Stage Iv ◽  
Angiogenic Factors ◽  
Response To Therapy ◽  
Stage Iiib ◽  
Blood Levels

7196 Background: VEGF and bFGF are among the most important angiogenic factors. We have explored these angiogenesis mediators in plasma and its prognostic significance in advanced NSCLC. Methods: Were enrolled 451 patients with advanced NSCLC, stages IIIB and IV and treated with cisplatin and docetaxel. Blood was collected before chemotherapy. Plasma VEGF and bFGF levels were assessed by commercial ELISA (sensitivity 5 pg/ml). In parallel plasma from 32 age and gender-matched controls was used. Results: Median age was 61 years (35–82) and 84% were males. 99% had performance status 0–1. 84% were in stage IV and 16% in stage IIIB. The histological subtypes were: 32% squamous cell carcinoma, 50% adenocarcinoma, 14% anaplastic large cell, and 4% undifferentiated. 41% of the patients received second line chemotherapy. 1% achieved complete response (CR), 36% partial response (PR), 35% had stable disease (SD) and 28% progressive disease (PD). Patient’s median plasma levels of VEGF (20 pg/ml, [6–203]) differ significantly (p = 0.04) from controls (14 pg/ml, [7–53]), but in contrast bFGF levels were not different, 14 pg/ml [5–960] vs 10 pg/ml [6–278] respectively. There were not differences in patients according to histology, site of metastasis and ECOG; however we could observe a tendency with stage for both factors: bFGF 9 pg/ml [5–24] in stage IIIB vs 15 pg/ml [6–960], p = 0.071 and VEGF 17 pg/ml [6–145] in IIIB vs 21 pg/ml [6–203] in IV, p = 0.086. It could not be observed any differences in response to therapy for both angiogenic factors; CR+PR patients presented median VEGF of 18 pg/ml [6–71] and bFGF 11 pg/ml [6–960] vs 20 pg/ml of VEGF [6–203] and 15 pg/ml of bFGF [5–395] in the SD+PD group. In the multivariate analysis we could not find that VEGF and bFGF plasma levels were predictors for time to progression (TTP) and overall survival (OS). Conclusions: VEGF but not bFGF levels in patients are significantly higher in patients than in controls. In our cohort of patients with advanced NSCLC we have not found any relationship between serum VEGF and bFGF levels with stage, histology, response, site of metastasis, TTP and OS. No significant financial relationships to disclose.

The quantification of the catalytic subunit of telomerase in plasma is a prognostic factor in advanced non-small cell lung cancer (NSCLC) patients

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7052-7052
Author(s):  
R. Sirera ◽  
C. Camps ◽  
L. Llobat ◽  
A. Berrocal ◽  
R. M. Bremnes ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Performance Status ◽  
Stage Iv ◽  
Large Cell ◽  
Complete Response ◽  
Response To Therapy ◽  
Catalytic Subunit ◽  
Stage Iiib ◽  
Circulating Dna ◽  
Nsclc Patients

7052 Background: Qualitative and quantitative analysis of circulating DNA in blood is a promising non-invasive diagnostic and prognostic tool. Our aim was to study the association between the free amount in plasma of the catalytic subunit of telomerase (hTERT) and several clinical variables in advanced NSCLC patients. Methods: We examined 451 NSCLC patients in stage IIIB and IV, treated with cisplatin and docetaxel. Blood samples were collected before chemotherapy, and circulating DNA was extracted from the serum using commercial adsorption columns. The amount of free hTERT in plasma was quantified by using RT-PCR. Results: Median age was 61 years [35–82] and 84% were males. 99% had performance status 0–1. 84% were in stage IV and 16% in stage IIIB. The histological subtypes were: 32% squamous cell carcinoma, 50% adenocarcinoma, 14% anaplastic large cell, and 4% undifferentiated. 41% of the patients received second line chemotherapy. 1% achieved complete response (CR), 36% partial response (PR), 35% had stable disease (SD) and 28% progressive disease (PD). Median hTERT value was 4856 ng/ml; for patients in IIIB was 4847 ng/ml [263–964826] and 4886 ng/ml [67–4373520] in stage IV (p = 0.75). There was not association between hTERT values and response to therapy, 20588 ng/ml [122–317251] in the CR+PR group vs 50204 ng/ml [67–4373520] in the SD+PD group (p = 0.09). hTERT values were not related with the localization of the metastasis. Dividing the cohort in two sets according to hTERT median we found two significantly different groups in terms of Overall Survival (OS) and Time To Progression (TTP). Patients with hTERT <4856 ng/ml had a median TTP of 5.3 months (m) [4.4–6.1] while for hTERT >4856 ng/ml was 4.1 m [3.5–4.6], (p = 0.0009). OS when hTERT <4856 ng/ml was 10.1m [4.9–11.3] and for hTERT >4856 ng/ml was 8.4 m [7.2–9.5], (p = 0.01). In the multivariate analysis, hTERT was an independent predictive variable for TTP (HR 1.39, CI 95% 1.1–1.7, p = 0.002) and OS (HR 1.27, CI 95% 1.1–1.6, p = 0.04). Conclusions: In advanced NSCLC patients, the quantification of free circulating hTERT in plasma is an affordable and valuable prognostic marker. High plasma hTERT levels are a poor prognostic indicator for TTP and OS. No significant financial relationships to disclose.

Analysis of nerve growth factor (NGF) blood levels in patients with advanced non-small cell lung cancer patients (NSCLC): Its correlation with clinical outcome

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17025-17025
Author(s):  
A. Blasco ◽  
R. Sirera ◽  
C. Camps ◽  
V. Giner ◽  
L. Llobat ◽  
...  
Keyword(s):  
Plasma Levels ◽  
Advanced Nsclc ◽  
Stage Iv ◽  
Large Cell ◽  
Complete Response ◽  
Response To Therapy ◽  
Blood Levels ◽  
Dependent Manner ◽  
Lung Cancer Patients ◽  
Response Site

17025 Background: Platinum compounds and taxanes have severe side effects in a dose and time-dependent manner, especially neurotoxicity. NGF plays an important role in growth and differentiation of neuronal components. Our goal was to study NGF levels in plasma and correlate it with patient’s clinico-pathologic characteristics. Methods: The study was performed with 451 patients with advanced NSCLC, stages IIIB-IV and treated with cisplatin and docetaxel. Peripheral blood was collected before therapy. NGF were assessed by commercial ELISA (detection limit, 5 pg/ml). Plasma from 32 age and gender-matched controls was used. Results: 91% of males, mean age 61 y [35–82]. 86 patients in ECOG PS 0–1 and 14 PS2. 71% in stage IV and 29% in IIIB. The histological subtypes were 38% squamous cell, 37% adenocarcinoma, 5% anaplasic large cell and 20% undifferentiated. 77.5% of the metastasis was out of the lung. Patients received a median of 6 cycles of chemotherapy [1–7]. 4% presented complete response (CR), 38% partial response (PR), 25% stable disease (SD) and 30% progressive disease (PD). Patient’s median plasma levels of NGF did not differ significantly from controls: 44 pg/ml [6–176] vs 31 pg/ml [14–144] respectively. There were not differences according to histology, site of metastasis and ECOG; however we could observe significant differences with stage: 25 pg/ml [10–70] in stage IIIB vs 47 pg/ml [6–176] in stage IV (p = 0.008). We could not observe any differences in response to therapy: CR+PR patients presented median NGF of 35 pg/ml [6–92] vs 39 pg/ml [10–165] in the SD+PD group. Splitting the cohort according to NGF median we found two significantly different groups in terms of Overall Survival (OS): patients with NGF <44 pg/ml had a median OS of 10.9 months (m) [7.9–13.9] vs 7.3 m [3–11.5] for patients with NGF >44 pg/ml (p = 0.03). In the multivariate analysis, NGF levels was not predictor for time to progression (TTP) and OS. Conclusions: NGF plasma levels did not differ in patients and controls. In our cohort with advanced NSCLC we have not found any relationship between NGF levels with histology, response, site of metastasis and TTP. By contrast NGF levels are higher in those patients in stage IV and in those presenting poorer OS. No significant financial relationships to disclose.

Nivolumab (NIVO) plus ipilimumab (IPI) versus chemotherapy (chemo) as first-line (1L) treatment for advanced non-small cell lung cancer (NSCLC): 4-year update from CheckMate 227.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9016-9016
Author(s):  
Luis G. Paz-Ares ◽  
Tudor-Eliade Ciuleanu ◽  
Jong-Seok Lee ◽  
Laszlo Urban ◽  
Reyes Bernabe Caro ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Performance Status ◽  
Stage Iv ◽  
Ecog Performance Status ◽  
Programmed Death ◽  
Long Term Follow Up ◽  
To Receive ◽  
Clinical Trial Information

9016 Background: 1L NIVO + IPI was shown to provide durable long-term overall survival (OS) benefit vs chemo regardless of tumor programmed death ligand 1 (PD-L1) expression in patients (pts) with advanced NSCLC in CheckMate 227 Part 1 (NCT02477826); 3-year OS rates were 33% vs 22% in pts with PD-L1 ≥ 1% (HR, 0.79 [95% CI, 0.67–0.93]) and 34% vs 15% in pts with PD-L1 < 1% (HR, 0.64 [95% CI, 0.51–0.81]). Here we report updated results from the study with 4 years’ minimum follow-up. Methods: Adults with previously untreated stage IV / recurrent NSCLC, no known EGFR/ ALK alterations , and ECOG performance status ≤ 1 were enrolled; pts were stratified by squamous (SQ) and non-squamous (NSQ) histology. Pts with PD-L1 ≥ 1% (n = 1189) were randomized 1:1:1 to receive NIVO (3 mg/kg Q2W) + IPI (1 mg/kg Q6W), NIVO alone (240 mg Q2W), or chemo. Pts with PD-L1 < 1% (n = 550) were randomized 1:1:1 to receive NIVO + IPI, NIVO (360 mg Q3W) + chemo, or chemo. OS with NIVO + IPI vs chemo in pts with PD-L1 ≥ 1% was the primary endpoint. Results: With minimum follow-up of 49.4 months (database lock, Feb 18, 2021), pts were at least 2 years beyond the protocol-specified end of immunotherapy treatment. Pts with PD-L1 ≥ 1% continued to show durable benefit with NIVO + IPI vs chemo (HR, 0.76 [95% CI, 0.65–0.90]); 4-year OS rates were 29% (NIVO + IPI), 21% (NIVO), and 18% (chemo). At 4 years, 14% (NIVO + IPI), 10% (NIVO), and 4% (chemo) remained progression free. Among responders, 34%, 30%, and 7% remained in response, respectively. In an exploratory analysis in pts with PD-L1 ≥ 50%, 4-year OS rates were 37% (NIVO + IPI), 26% (NIVO), and 20% (chemo). In pts with PD-L1 < 1%, OS HR for NIVO + IPI vs chemo was 0.64 (95% CI, 0.51–0.81); 4-year OS rates were 24% (NIVO + IPI), 13% (NIVO + chemo) and 10% (chemo). At 4 years, 12% (NIVO + IPI), 7% (NIVO + chemo), and 0% (chemo) remained progression free. Among responders, 31%, 13%, and 0% remained in response, respectively. Among pts who progressed on NIVO + IPI vs chemo, 7% vs 40% (PD-L1 ≥ 1%), and 9% vs 33% (PD-L1 < 1%), received subsequent immunotherapy. Benefit with NIVO + IPI vs chemo was observed for both SQ and NSQ histology (Table). With long-term follow-up, no new safety signals were identified. Conclusions: With 4 years’ minimum follow-up, 1L NIVO + IPI continued to provide durable, long-term OS benefit vs chemo in pts with advanced NSCLC regardless of PD-L1 expression or histology. Clinical trial information: NCT02477826. [Table: see text]

TAMI-19. IMMUNOHISTOLOGICAL ANALYSIS OF ANGIOGENIC FACTORS OTHER THAN VEGF IN GLIOBLASTOMAS IN RELATION TO THE USE OF BEVACIZUMAB

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi202-vi202
Author(s):  
Taketo Ezaki ◽  
Ryota Tamura ◽  
Toshihide Tanaka ◽  
Yuki Kuranari ◽  
Keisuke Miyake ◽  
...  
Keyword(s):  
Growth Factor ◽  
Performance Status ◽  
Progression Free Survival ◽  
Angiogenic Factors ◽  
In Situ Observation ◽  
Newly Diagnosed ◽  
Naive Group ◽  
Paired Samples ◽  
Initial Surgery ◽  
Effective Group

Abstract Although bevacizumab was shown to improve progression-free survival and performance status of the patients with high-grade gliomas, clinical trials consistently showed lack of benefit in terms of patients’ overall survival. The recurrent tumors are inevitably more aggressive and invasive as compared with the original tumors, and the in-situ observation in actual human specimens is essential to elucidate the mechanism of resistance. In Japan, bevacizumab was approved not only for recurrent but also for newly diagnosed cases. The safety as well as efficacy of resection following neoadjuvant bevacizumab has been reported, and a phase II study is currently ongoing (UMIN-000025579). In the present study, the expression of angiogenic factors other than VEGF (basic fibroblast growth factor (bFGF), placenral growth factor (PlGF), angiopoietin1/2 and ephrinA2) was investigated by immunohistochemistry to be compared among tumors with no previous bevacizumab treatment, those resected following bevacizumab, and those refractory to bevacizumab. Fifty-nine samples from 42 patients were included; 24 of newly diagnosed glioblastomas with no previous bevacizumab (naïve group), 16 resected following neoadjuvant bevacizumab (effective group), and 6 resected after recurrence or autopsied (refractory/autopsied group). 12 were paired samples (8 naïve and refractory, 4 effective and refractory). The expression of PlGF significantly increased in the effective group as compared with the naïve group (p=0.003). In the paired specimens, there was a trend towards increased expression of PlGF in the second specimens (refractory/autopsied group) as compared with the specimens of initial surgery (p=0.083). Angiopoietin1, angiopoietin2 and ephrinA2 were characteristically expressed in the microvessels less than 15μm. The increased expression of PlGF might be associated with the recurrence after bevacizumab.

T-cell lymphomas: immunologic, histologic, clinical, and therapeutic analysis of 63 cases.

1988 ◽  
Vol 6 (10) ◽  
pp. 1584-1589 ◽  
Author(s):  
B Coiffier ◽  
F Berger ◽  
P A Bryon ◽  
J P Magaud
Keyword(s):  
T Cell ◽  
Clinical Presentation ◽  
Performance Status ◽  
Stage Iv ◽  
Poor Performance ◽  
Large Cell ◽  
Response To Therapy ◽  
Poor Performance Status ◽  
T Cell Lymphomas ◽  
Stage Iv Disease

Sixty-three patients with T-cell lymphoma (TCL) were analyzed to correlate morphological and immunological features with clinical presentation, response to therapy, and survival. Clinical presentation was severe, with 59% of patients having stage IV disease, 60% B symptoms, 35% poor performance status, 44% large tumoral mass, and 40% a high number of extranodal localizations. Morphological subtypes were small-cell in four cases, diffuse-mixed in 29 cases, monomorphic medium-sized in two cases, immunoblastic in 21 cases, anaplastic large-cell in four cases, and unclassified in three cases. Immunological phenotypes were immature T in 11 cases, CD4 in 26 cases, CD8 in 13 cases, and undefined (CD4 + CD8) in ten cases. Response to therapy was poor except for the 39 patients treated by an intensive and sequential regimen (non-Hodgkin's lymphoma [LNH]-80 or LNH-84) that gave a 77% complete remission (CR) rate with a 23% relapse rate. Median survival was 35 months. No correlation was found between morphological subtypes and other variables. Helper (CD4) phenotype seemed to have a better prognosis than other phenotypes. Variables associated with long survival for all the patients were localized disease and absence of large tumoral mass and for the subgroup of patients treated by the LNH regimens CD4 phenotype, absence of B symptoms, absence of a large tumoral mass, and less than two extranodal sites of disease.

Phase II Trial of Paclitaxel Plus Gemcitabine in Patients With Locally Advanced or Metastatic Non–Small-Cell Lung Cancer

2001 ◽  
Vol 19 (4) ◽  
pp. 1071-1077 ◽  
Author(s):  
Dolores Isla ◽  
Rafael Rosell ◽  
José J. Sánchez ◽  
Alfredo Carrato ◽  
Enriqueta Felip ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Median Survival ◽  
Response Rate ◽  
Performance Status ◽  
Locally Advanced ◽  
Stage Iv ◽  
Small Cell ◽  
Stage Iiib ◽  
Small Cell Lung ◽  
A Performance

PURPOSE: Given the cisplatin-related myelotoxicity and nonhematologic toxicities, we were prompted to undertake a study of the noncisplatin combination of paclitaxel plus gemcitabine to evaluate the efficacy, tolerance, and survival of this combination in patients with locally advanced and metastatic non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients received gemcitabine 2,000 mg/m2 and paclitaxel 150 mg/m2 on days 1 and 15 of a 28-day cycle, for a maximum of eight cycles. RESULTS: Between December 1997 and June 1998, 89 untreated NSCLC patients were enrolled; 30 (34%) had stage IIIB disease (23 with malignant pleural effusion and seven without), and 59 (66%) had stage IV disease. Eighty-six percent of patients had a performance status of 0 or 1. The median number of cycles administered was four (range, one to eight cycles). The mean dose-intensity for both paclitaxel and gemcitabine was nearly 100%. Hematologic and nonhematologic toxicities were mild. Thirty-eight patients received second-line chemotherapy after completion of the study. The overall intent-to-treat response rate was 32.2%, with a higher response rate for stage IIIB patients (43.3%) than for stage IV patients (26.3%). Overall median survival was 9.9 months, and 1-year survival was 38.8% (14.2 months for stage IIIB and 7.7 months for stage IV; P = .007). Median survival was 10.2 months for patients with a performance status of 0 or 1 and 4.8 months for patients with a performance status of 2 (P = .007). CONCLUSION: A biweekly paclitaxel/gemcitabine regimen was well tolerated, with an acceptable response rate and a reasonable median survival time, especially in patients with good performance status. It merits further exploration in future studies.

Angiogenesis in acute and chronic leukemias and myelodysplastic syndromes

Blood ◽  
2000 ◽  
Vol 96 (6) ◽  
pp. 2240-2245 ◽  
Author(s):  
Alvaro Aguayo ◽  
Hagop Kantarjian ◽  
Taghi Manshouri ◽  
Cristi Gidel ◽  
Elihu Estey ◽  
...  
Keyword(s):  
Growth Factor ◽  
Blood Vessels ◽  
Myelodysplastic Syndromes ◽  
Plasma Levels ◽  
Myeloid Leukemia ◽  
Lymphoblastic Leukemia ◽  
Angiogenic Factors ◽  
Bone Marrow Biopsies ◽  
Tnf Α ◽  
Factor Α

Abstract Angiogenesis has been associated with the growth, dissemination, and metastasis of solid tumors. The aims of this study were to evaluate the vascularity and the levels of angiogenic factors in patients with acute and chronic leukemias and myelodysplastic syndromes (MDS). The numbers of blood vessels were measured in 145 bone marrow biopsies and the levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), tumor necrosis growth factor-α (TNF-α), tumor growth factor-α (TGF-α), and hepatocyte growth factor (HGF) were determined in 417 plasma samples. Except for chronic lymphocytic leukemia (CLL), vascularity was significantly higher in all leukemias and MDS compared with control bone marrows. The highest number of blood vessels and largest vascular area were found in chronic myeloid leukemia (CML). VEGF, bFGF, and HGF plasma levels were significantly increased in acute myeloid leukemia (AML), CML, CLL, chronic myelomonocytic leukemia (CMML), and MDS. HGF, TNF-α, and bFGF but not VEGF were significantly increased in acute lymphoblastic leukemia (ALL). TNF-α levels were significantly increased in all diseases except for AML and MDS. No significant increase was found in TGF-α in any leukemia or MDS. The highest plasma levels of VEGF were in CML, and the highest plasma levels of bFGF were in CLL. The levels of HGF were highest in CMML. These data suggest that vascularity and angiogenic factors are increased in leukemias and MDS and may play a role in the leukemogenic process.

Correlation Between Clinical Responses and Immune Characteristics in Patients with Relapsed CLL Treated with Ofatumumab and Lenalidomide

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1748-1748
Author(s):  
Candida Vitale ◽  
Lorenzo Falchi ◽  
Elisa ten Hacken ◽  
Hui Gao ◽  
Hila Shaim ◽  
...  
Keyword(s):  
Immune System ◽  
Nk Cells ◽  
Plasma Levels ◽  
Research Funding ◽  
Cell Function ◽  
Nk Cell ◽  
Advisory Board ◽  
Angiogenic Factors ◽  
Response To Therapy ◽  
Clinical Responses

Abstract Chronic lymphocytic leukemia (CLL) is characterized by phenotypical and functional alterations of different host immune components. Lenalidomide is an immunomodulatory agent which exerts both a direct antitumor effect and a pleiotropic activity on the immune system. Single-agent lenalidomide is active in patients with relapsed and refractory CLL, and the addition of an anti-CD20 monoclonal antibody to lenalidomide has shown synergism in vitro, as well as improved clinical responses in vivo. We designed a phase II study with the aim of determining the efficacy and tolerability of combined ofatumumab and lenalidomide for the treatment of relapsed or refractory CLL. We also wanted to investigate whether immune system and tumor microenvironment characteristics, such as circulating T and NK cell number and function, and plasma levels of chemokines, cytokines, and angiogenic factors could be correlated with the response to treatment and could be modulated during the course of the therapy. Ofatumumab was administered at a dose of 300 mg on day 1, 1000 mg on days 8, 15, and 22 during course 1, 1000 mg on day 1 during courses 3-6, and once every other course on day 1 during courses 7-24 (28-day courses). Lenalidomide (10 mg daily) was started on day 9 and continued for as long as a clinical benefit was observed. Thirty-four patients were enrolled. The overall response rate was 71%. Eight patients (24%) achieved a complete remission (CR) or CR with incomplete recovery of blood counts, including 9% with minimal residual disease-negative CR. The median progression-free survival was 16 months, and the estimated 5-year survival was 53%. The most common treatment-related toxicity was neutropenia (grade >2 in 18% of the 574 patient-courses). The most frequent infectious complications were pneumonia and neutropenic fever (24% and 9% of patients, respectively). For the correlative studies, peripheral blood mononuclear cells and plasma samples were collected at baseline and after 3, 6, 9, and 12 months of therapy. Lymphocyte subsets were analyzed by flow cytometry. T and NK cell function was evaluated on 9 patients based on the expression of CD107a, IFNγ, TNFα, and IL-2 after the exposure to CD3/CD28 magnetic beads and K562 cell line, respectively. Chemokines, cytokines, and angiogenic factors were quantified through a multiplex bead-based immunoassay. Thirty-four age-matched healthy donors (HD) were used as controls. Treatment with ofatumumab and lenalidomide decreased the number of circulating T and NK cells. The greatest decrease was observed after 3 months of therapy as compared to baseline (p≤0.02 for all comparisons). We found that the baseline number of CD4+ T cells and CD57+ CD56+ NK cells was higher in CR patients as compared to non responder (NR) patients (median absolute number 1595/μl vs. 715/μl, p=0.04, and 358/μl vs. 70/μl, p=0.02). We also compared baseline T and NK cell populations of CR patients to HD, and found that the former had significantly higher numbers of CD16+ CD56+ and CD57+ CD56+ NK cells (median 356/μl vs. 80/μl, p=0.03, and 358/μl vs. 29/μl, p=0.0008). Interestingly, baseline numbers of CD16+ CD56+ and CD57+ CD56+ NK cells were comparable between NR patients and HD. We also observed that patients who achieved CR had significantly better T and NK cell function at baseline, whereas T and NK cell function was impaired in patients who only had partial or no response. Plasma levels of bFGF, VEGF and IFN-γ were significantly decreased at month 3 compared to baseline in all patients (p≤0.02 for all comparisons). Finally, significantly lower levels of circulating CCL2, CCL3, CCL4, IFNα, and IL-12p70 were detected during treatment in patients who achieved CR, compared to NR (p<0.05 for all comparisons). In conclusion, the combination of ofatumumab and lenalidomide is a well tolerated regimen that induces durable responses in the majority of patients with relapsed CLL, and sustained MRD-negative CR in some. A higher number and preserved functional activity of T and NK cells were found in responding patients at baseline, as compared to NR, underscoring the importance of a competent immune system in supporting the effectiveness of this type of treatment, and suggesting a need to further investigate these immune features as markers for prediction of response to therapy. Disclosures Faderl: Celgene Corp.: Other: Advisory Board. Wierda:Celgene Corp.: Consultancy; Glaxo-Smith-Kline Inc.: Research Funding. Rezvani:Pharmacyclics: Research Funding. Burger:Pharmacyclics LLC, an AbbVie Company: Research Funding. Keating:Glaxo-Smith-Kline Inc.: Other: Advisory board; Celgene Corp.: Consultancy.

Sign in / Sign up

Export Citation Format

Share Document