scholarly journals Expression of SOAT1 in Adrenocortical Carcinoma and Response to Mitotane Monotherapy: An ENSAT Multicenter Study

2020 ◽  
Vol 105 (8) ◽  
pp. 2642-2653 ◽  
Author(s):  
Isabel Weigand ◽  
Barbara Altieri ◽  
Amanda M F Lacombe ◽  
Vittoria Basile ◽  
Stefan Kircher ◽  
...  
Keyword(s):  
Protein Expression ◽  
Treatment Response ◽  
Adrenocortical Carcinoma ◽  
Advanced Disease ◽  
Hormone Secretion ◽  
Single Agent ◽  
Objective Response ◽  
Drug Effects ◽  
Progression Free Survival ◽  
Free Survival

Abstract Context Objective response rate to mitotane in advanced adrenocortical carcinoma (ACC) is approximately 20%, and adverse drug effects are frequent. To date, there is no marker established that predicts treatment response. Mitotane has been shown to inhibit sterol-O-acyl transferase 1 (SOAT1), which leads to endoplasmic reticulum stress and cell death in ACC cells. Objective To investigate SOAT1 protein expression as a marker of treatment response to mitotane. Patients A total of 231 ACC patients treated with single-agent mitotane as adjuvant (n = 158) or advanced disease therapy (n = 73) from 12 ENSAT centers were included. SOAT1 protein expression was determined by immunohistochemistry on formalin-fixed paraffin-embedded specimens. Setting Retrospective study at 12 ACC referral centers. Main outcome measure Recurrence-free survival (RFS), progression-free survival (PFS), and disease-specific survival (DSS). Results Sixty-one of 135 patients (45%) with adjuvant mitotane treatment had recurrences and 45/68 patients (66%) with mitotane treatment for advanced disease had progressive disease. After multivariate adjustment for sex, age, hormone secretion, tumor stage, and Ki67 index, RFS (hazard ratio [HR] = 1.07; 95% confidence interval [CI], 0.61-1.85; P = 0.82), and DSS (HR = 1.30; 95% CI, 0.58-2.93; P = 0.53) in adjuvantly treated ACC patients did not differ significantly between tumors with high and low SOAT1 expression. Similarly, in the advanced stage setting, PFS (HR = 1.34; 95% CI, 0.63-2.84; P = 0.45) and DSS (HR = 0.72; 95% CI, 0.31-1.70; P = 0.45) were comparable and response rates not significantly different. Conclusions SOAT1 expression was not correlated with clinical endpoints RFS, PFS, and DSS in ACC patients with mitotane monotherapy. Other factors appear to be relevant for mitotane treatment response and ACC patient survival.

scholarly journals Phase II trial of the IDO pathway inhibitor indoximod plus pembrolizumab for the treatment of patients with advanced melanoma

2021 ◽  
Vol 9 (6) ◽  
pp. e002057
Author(s):  
Yousef Zakharia ◽  
Robert R McWilliams ◽  
Olivier Rixe ◽  
Joseph Drabick ◽  
Montaser F Shaheen ◽  
...  
Keyword(s):  
Phase Ii ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Complete Response ◽  
Advanced Melanoma ◽  
Free Survival ◽  
Programmed Death ◽  
Evaluable Population

BackgroundThe indoleamine 2,3-dioxygenase (IDO) pathway is a key counter-regulatory mechanism that, in cancer, is exploited by tumors to evade antitumor immunity. Indoximod is a small-molecule IDO pathway inhibitor that reverses the immunosuppressive effects of low tryptophan (Trp) and high kynurenine (Kyn) that result from IDO activity. In this study, indoximod was used in combination with a checkpoint inhibitor (CPI) pembrolizumab for the treatment for advanced melanoma.MethodsPatients with advanced melanoma were enrolled in a single-arm phase II clinical trial evaluating the addition of indoximod to standard of care CPI approved for melanoma. Investigators administered their choice of CPI including pembrolizumab (P), nivolumab (N), or ipilimumab (I). Indoximod was administered continuously (1200 mg orally two times per day), with concurrent CPI dosed per US Food and Drug Administration (FDA)-approved label.ResultsBetween July 2014 and July 2017, 131 patients were enrolled. (P) was used more frequently (n=114, 87%) per investigator’s choice. The efficacy evaluable population consisted of 89 patients from the phase II cohort with non-ocular melanoma who received indoximod combined with (P).The objective response rate (ORR) for the evaluable population was 51% with confirmed complete response of 20% and disease control rate of 70%. Median progression-free survival was 12.4 months (95% CI 6.4 to 24.9). The ORR for Programmed Death-Ligand 1 (PD-L1)-positive patients was 70% compared with 46% for PD-L1-negative patients. The combination was well tolerated, and side effects were similar to what was expected from single agent (P).ConclusionIn this study, the combination of indoximod and (P) was well tolerated and showed antitumor efficacy that is worth further evaluation in selected patients with advanced melanoma.

scholarly journals CTLA4 promoter methylation predicts response and progression-free survival in stage IV melanoma treated with anti-CTLA-4 immunotherapy (ipilimumab)

2020 ◽  
Author(s):  
Simon Fietz ◽  
Romina Zarbl ◽  
Dennis Niebel ◽  
Christian Posch ◽  
Peter Brossart ◽  
...  
Keyword(s):  
Protein Expression ◽  
Promoter Methylation ◽  
Single Agent ◽  
Stage Iv ◽  
Predictive Biomarkers ◽  
Progression Free Survival ◽  
Immune Checkpoint Blockade ◽  
Response To Treatment ◽  
Free Survival ◽  
Stage Iv Melanoma

AbstractAnti-CTLA-4-antibodies can induce long-lasting tumor remissions. However, only a few patients respond, necessitating the development of predictive companion biomarkers. Increasing evidence suggests a major role of epigenetics, including DNA methylation, in immunology and resistance to immune checkpoint blockade. Here, we tested CTLA4 promoter methylation and CTLA-4 protein expression as predictive biomarkers for response to anti-CTLA-4 immunotherapy. We identified retrospectively N = 30 stage IV melanoma patients treated with single-agent anti-CTLA-4 immunotherapy (ipilimumab). We used quantitative methylation-specific PCR and immunohistochemistry to quantify CTLA4 methylation and protein expression in pre-treatment samples. CTLA4 methylation was significantly higher in progressive as compared to responding tumors and significantly associated with progression-free survival. A subset of infiltrating lymphocytes and tumor cells highly expressed CTLA-4. However, CTLA-4 protein expression did not predict response to treatment. We conclude that CTLA4 methylation is a predictive biomarker for response to anti-CTLA-4 immunotherapy.

scholarly journals Agnostic Evaluation of Ipilimumab and Nivolumab Association: A Metanalysis.

2020 ◽  
Author(s):  
Paolo Marchetti ◽  
Andrea Botticelli ◽  
Antonio Paolo Ascierto ◽  
Giuseppe Curigliano ◽  
Diana Giannarelli
Keyword(s):  
Meta Analysis ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Added Value ◽  
Combination Strategy ◽  
Free Survival ◽  
Multiple Tumor ◽  
Single Agent Therapy ◽  
Tumor Types

Abstract Background. Ipilimumab and Nivolumab, targeting the molecules CTLA-4, PD-1, respectively, have shown efficacy against several types of cancer. Despite these results, only a small percentage of patients maintain a long-lasting effect. Even Ipilimumab, in combination with nivolumab, has demonstrated a significant clinical benefit in multiple tumor types. However, no trial has been designed with the primary endpoint to compare the efficacy of nivolumab plus ipilimumab combined, compared to nivolumab alone. Hence, the added value of ipilimumab in the combination has not clearly been established yet. The aim of this study was to demonstrate the superiority of the combination strategy compared to single agent therapy.Materials and methods. We performed a meta-analysis of Phase I-II-III Clinical Trials, published from 2010 up to 2020, in which the combination of ipilimumab plus nivolumab was compared to nivolumab alone. We extracted ORR, OS and PFS HR on the basis of treatment from the subgroup analysis of each trial. Results. A total of 8 trials were included in the present meta-analysis. Overall, 1313 patients were treated with the nivolumab plus ipilimumab combination compared to 1110 patients treated with nivolumab alone. All trials reported the Objective response rate (ORR) (Table 2), no heterogeneity was found and the pooled Odds Ratio (Figure 1) was highly in favor of the nivolumab plus ipilimumab combination with respect to nivolumab alone (1.683; 95% CI: 1.407-2.012; P<0.0001). Three studies were considered for Progression free survival (PFS) analysis (Table 3), no heterogeneity was found and the pooled Hazard Ratio (Figure 2) favored the combination of nivolumab plus ipilimumab with respect to nivolumab alone (0.807; 95% CI: 0.719-0.907; P<0.0001). The Overall survival (OS) endpoint was considered only in 2 trials (Table 4), no heterogeneity was found and the pooled HR (Figure 3) favored, also in this case, the combination of nivolumab plus ipilimumab with respect to nivolumab alone (0.87; 95% CI: 0.763-0.997; P=0.045).Conclusions. The combination of ipilimumab plus nivolumab seems to be superior to nivolumab alone in cancer patients, regardless of histology.

scholarly journals SAT-165 Sterol O-Acyl Transferase 1 as a Prognostic Marker of Adrenocortical Carcinoma

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Amanda Meneses Ferreira Lacombe ◽  
Iberê Cauduro Soares ◽  
Helaine da Silva Charchar ◽  
Vânia Balderrama Brondani ◽  
João Evangelista Bezerra Neto ◽  
...  
Keyword(s):  
Overall Survival ◽  
Protein Expression ◽  
Adrenocortical Carcinoma ◽  
Progression Free Survival ◽  
Disease Stage ◽  
Acyl Transferase ◽  
Surgical Specimen ◽  
Free Survival ◽  
Tertiary Center ◽  
The Impact

Abstract Background: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with an unfavorable prognosis. Despite the poor prognosis in the majority of patients, no improvements in treatment strategies have been achieved, largely due to the rarity of these tumors. Therefore, the discovery of new prognostic biomarkers that could guide and improve the management of patients with ACC is of enormous interest. Sterol-O-Acyl Transferase 1 (SOAT1) is involved in cholesterol esterification in adrenocortical cells. Recently, it was demonstrated that SOAT1 inhibition leads to impaired steroidogenesis and cell viability in ACC [1]. There are no studies so far addressing the impact of SOAT1 protein expression in ACC prognosis and clinical outcomes. Methods: We evaluated SOAT1 protein expression by immunohistochemistry (ab39327; 1:4000; Abcam, EUA) in a tissue microarray of 107 adrenocortical carcinomas (Weiss score ≥ 3) from adult patients treated in a single tertiary center in Brazil. Immunohistochemistry results were evaluated through a semiquantitative approach by two independent pathologists. We aimed to evaluate the correlation of SOAT1 protein expression with clinical and biochemical parameters, surgical specimen histological characteristics, recurrence free-survival, progression free-survival and overall survival. Results: SOAT1 protein expression was heterogenous in this cohort; 38% of ACCs demonstrated strong SOAT1 protein expression while 62% demonstrated weak or absent SOAT1 protein expression. Strong SOAT1 protein expression correlates with known features of high aggressiveness in ACC, such as excessive tumor cortisol secretion (p= 0.007), advanced disease stage [ENSAT 3 and ENSAT 4 (p= 0.009)] and high Ki67 index (0.008). On multivariate analysis, strong SOAT1 protein expression was an independent predictor of lower overall survival (HR 1.71, CI 95% 1.05-2.92; p= 0.04) when considering all cases (n= 107) and of lower progression free survival (HR 3.05, CI 95% 1.05-8.85; p= 0.04) in patients with metastatic disease at diagnosis (n= 22). Conclusions: Our findings demonstrated that SOAT1 protein expression has prognostic value in ACC and reinforce the importance of investigating SOAT1 as a possible therapeutic target for patients with ACC. Multicentric prospective studies including a larger number of patients are needed in order to validate and consolidate the results found in this cohort. References: 1. Sbiera S, Leich E et al. Mitotane inhibits Sterol-O-Acyl Transferase 1 Triggering Lipid-Mediated Endoplasmic Reticulum Stress and Apoptosis in Adrenocortical Carcinoma Cells. Endocrinology. 2015; 156 (11):3895-908.

Anti-PD-1/PD-L1 plus chemotherapy versus chemotherapy alone in first-line treatment for patients with metastatic NSCLC that were PD-L1 negative or less than 1%.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9061-9061
Author(s):  
Thierry Landre ◽  
Gaetan Des Guetz ◽  
Kader Chouahnia ◽  
Cherifa Taleb ◽  
Alain Vergnenegre ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Meta Analysis ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
Study Heterogeneity ◽  
Duration Of Response ◽  
Line Setting

9061 Background: Clinical efficacy of single agent anti-PD-1/PD-L1 in patients with Non-Small-Cell-Lung-Cancer (NSCLC) that were PD-L1 negative or < 1% is controversial. Recent studies have evaluated the combination of anti-PD-1/PD-L1 to chemotherapy (CT) for this population in the first line setting. Methods: We performed a meta-analysis (MA) of randomized trials that compared PD-1/PD-L1 inhibitor plus CT with CT alone in first line of treatment for advanced NSCLC. The outcomes included overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) in patients with undetectable PD-L1 expression or < 1%. A fixed-effect or random-effects model was adopted depending on between-study heterogeneity. Results: Four studies evaluated atezolizumab + CT (IMpower 130,131,132 and 150), three studies pembrolizumab + CT (Keynote 021, 189 and 407) and one study evaluated nivolumab + CT (CheckMate 227). The eight eligible studies included 2037 patients (1246 with PD-L1 negative and 791 with PD-L1 expression < 1%). Most of the patients were men and smokers, with a median age of 64 years. There were 1423 Non-squamous (69.8 %) and 614 Squamous tumors (30%). The combination (PD-1/PD-L1 inhibitor + CT) was significantly associated with improvement of OS (hazards ratio [HR], 0.75; 95% CI 0.63–0.89; p < 0.0001), PFS (HR, 0.72; 95% CI 0.65–0.80; p < 0.0001) and ORR (relative ratio [RR], 2.59; 95% CI 1.46–4.60; p < 0.0001). Moreover, median duration of response (DOR) was statistically longer with combination (8.1 months versus 4.9; p < 0.0008). Conclusions: For patients with untreated NSCLC with low ( < 1%) or undetectable PD-L1 expression, the anti-PD-1/PD-L1 combination with chemotherapy, compared with chemotherapy alone, is associated with significantly improved OS, PFS, and ORR.

scholarly journals Use of first-line trabectedin in advanced leiomyosarcoma: a review of clinical data and future perspectives

2016 ◽  
Vol 4 (1) ◽  
pp. 6-10
Author(s):  
Nadia Hindi ◽  
Florence Duffaud ◽  
Giacomo Giulio Baldi ◽  
Patricia Pautier
Keyword(s):  
Clinical Trials ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
First Line Therapy ◽  
Large Subgroup ◽  
Myxoid Liposarcomas ◽  
Line Setting

Leiomyosarcomas (LMS) represent a large subgroup of soft-tissue sarcoma (STS) generally considered moderately sensitive to conventional chemotherapy. Single-agent doxorubicin is the standard first-line therapy for advanced non-selected STS, although combination with ifosfamide appears to be superior in terms of objective response. Gemcitabine-based regimes, dacarbazine, trabectedin and pazopanib seem to be especially active in patients with advanced LMS, while the activity of ifosfamide in this histotype is low. Data derived from clinical trials and retrospective series show that trabectedin is especially active in L-sarcomas including non-gynecological and uterine LMS as well as liposarcomas, in particular myxoid liposarcomas. Trabectedin has also been tested in the first-line setting, alone or in combination with doxorubicin, for the treatment of LMS of uterine and non-uterine origin in a trial by the French Sarcoma Group (phase II study LMS-02) with encouraging results in terms of median progression-free survival and objective response. The toxicity profile of trabectedin appears to be comparable to, or even more manageable than, that of other chemotherapy combinations in the first-line setting. Designing new clinical trials based on specific histologic subtypes is feasible, and the results of such studies would help to optimize the management of patients with STS.

scholarly journals CTNI-37. EFFICACY OF ONC201 IN PATIENTS WITH ONC201 FOR RECURRENT H3 K27M-MUTANT DIFFUSE MIDLINE GLIOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii50-ii51
Author(s):  
Isabel Arrillaga-Romany ◽  
Sylvia Kurz ◽  
Rohinton S Tarapore ◽  
Ashley Sumrall ◽  
Nicholas Butowski ◽  
...  
Keyword(s):  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Integrated Analysis ◽  
Low Grade ◽  
Free Survival ◽  
Rano Criteria ◽  
Dismal Prognosis ◽  
T1 Contrast ◽  
Diffuse Midline Glioma

Abstract H3 K27M-mutant diffuse midline gliomas (DMG) have a dismal prognosis. We report an integrated analysis for ONC201, a DRD2 antagonist and ClpP agonist, in patients with recurrent H3 K27M DMG administered as monotherapy in 3 clinical studies (NCT03295396, n=20; NCT02525692, n=6; or expanded access, n=4) by independent, central radiology review among 30 patients. At baseline, patients had measurable contrast-enhancing disease by RANO criteria, KPS&gt;60, and were &gt;90 days from prior radiation. Patients with primary lesions that involved the pons or spinal cord or had evidence of leptomeningeal or cerebrospinal fluid dissemination were excluded. ONC201 was orally administered at 625 mg (scaled by body weight for patients &lt; 18 years old) weekly in 29 patients and every 3 weeks in 1 patient. Median age was 31 years (range 8–70; two patients &lt; 18). There were 16 women and 14 men. Tumors were predominantly thalamic (73%), with other locations including the cerebellum (5%), brainstem (non-pontine) (3%), basal ganglia (3%), and midbrain (3%). Median time from prior radiation was 7.5 months. The most frequent drug-related adverse events were low grade nausea (10%) and fatigue (10%). Nine patients (30%) had &gt;50% regression of T1 contrast enhancement and 11 (36.7%) patients had regression of T2/FLAIR. Objective response rate and progression-free survival by RANO criteria, as well overall survival will be reported. Among 8 patients with sustained radiographic regressions, 6 were tapered off dexamethasone and 4 had improvement in KPS. Five patients (16.7%) remain on treatment with a median of 9.5 months (range 7.3–12). In conclusion, single agent ONC201 is well tolerated and clinically active in recurrent H3 K27M DMG patients.

scholarly journals CTNI-53. SINGLE ARM, OPEN-LABEL, MULTICENTER PHASE II STUDY OF THE RADIONUCLIDE 177LU-DOTATATE (LUTATHERA) IN ADULTS WITH ADVANCED INTRACRANIAL MENINGIOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii54-ii55
Author(s):  
Sylvia Kurz ◽  
Elcin Zan ◽  
Jasone Gurewitz ◽  
Christine Cordova ◽  
Andrea B Troxel ◽  
...  
Keyword(s):  
Treatment Response ◽  
Phase Ii ◽  
Progressive Disease ◽  
Phase Ii Study ◽  
Somatostatin Receptor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Free Survival ◽  
Intracranial Meningiomas ◽  
Promising Treatment

Abstract BACKGROUND Meningiomas are the most common primary intracranial neoplasm. Once surgical and radiotherapeutic options are exhausted, there are no effective medical treatments available. A majority of meningiomas express somatostatin receptor 2 (SSTR2), representing a promising treatment target. 177Lu-DOTATATE is a SSTR2-targeting radionuclide that has been successful in SSTR2-expressing neuroendocrine tumors. Here we hypothesize that 177Lu-DOTATATE is effective in treating progressive intracranial meningiomas. METHODS In this ongoing phase II study (NCT03971461), adults with advanced intracranial meningiomas received 177Lu-DOTATATE 7.4 GBq (200 mCi) every 8 weeks for 4 doses. 68Ga-DOTATATE PET-MRI was obtained before and at the end of treatment (EOT). The primary endpoint was progression-free survival at 6 months (PFS-6). Correlative studies evaluated the association of PFS-6, objective response rate, progression-free survival, overall survival with radiographic tumor measurements, 68Ga-DOTATATE uptake on PET-MRI, SSTR2 expression in tumor, and meningioma methylation subclass. RESULTS Nine patients (F = 7, M = 2) with progressive meningiomas (WHO I = 2, II = 6, III = 1) have been enrolled. Median age was 63 (range 49–78) years. All patients previously underwent tumor resection and at least one course of radiation. Treatment with 177Lu-DOTATATE was well tolerated, although CTCAE grade 3/4 electrolyte derangements and cytopenias were observed. Six patients reached PFS-6, three patients experienced progressive disease. Four patients had EOT 68Ga-DOTATATE PET-MRI evaluations in which anatomic measurements and 68Ga-DOTATATE standardized uptake values (SUV) pre- and post-treatment were assessed: one patient had reduced SUV measurements in all target lesions indicating altered SSTR2 expression and functional treatment response, one patient had stable disease, one patient had a mixed treatment response, and one patient experienced progressive disease. CONCLUSIONS SSTR2-targeting 177Lu-DOTATATE represents a promising treatment option for patients with progressive intracranial meningiomas. Treatment is well tolerated and can lead to functional alteration of tumoral SSTR2 expression by 68Ga-DOTATATE PET-MR imaging.

scholarly journals Efficacy of EDP ± mitotane chemotherapy in the treatment of metastatic adrenocortical carcinoma. Predictive and prognostic factors of efficacy

2021 ◽  
Vol 11 (1) ◽  
pp. 37-46
Author(s):  
Ya. A. Zhulikov ◽  
E. I. Kovalenko ◽  
V. Yu. Bohyan ◽  
M. V. Khoroshilov ◽  
M. M. Gabrava ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Adrenocortical Carcinoma ◽  
Median Overall Survival ◽  
Therapeutic Option ◽  
Objective Response ◽  
Group Versus ◽  
Progression Free Survival ◽  
Ki 67 ◽  
Free Survival ◽  
Effective Therapeutic Option

Introduction. Adrenocortical carcinoma (ACC) is an orphan disease with an unfavorable prognosis. The most effective therapeutic option in the treatment of ACC is EDP plus mitotane combination chemotherapy. However, no studies comparing the efficacy of the EDP regimen with or without mitotane have been published.Materials and methods. A retrospective analysis of health records of patients with histologically confirmed metastatic ACC, who received at least one chemotherapy cycle with EDP ± mitotane. The study included 73 patients, 49 of which received a combination of EDP and mitotane and 24 were treated with EDP chemotherapy.Results. The objective response rate was 18,4 % in the EDP + mitotane group versus 4,1 % in the EDP group. Disease control was reported in 25 (51 %) and 13 (54,2 %) patients, respectively. No significant differences were found in progression-free survival (PFS) rates between the EDP and EDP + mitotane groups; the median PFS rate was 6,5 and 6,0 months, respectively. The median overall survival (OS) in the total population was 20,9 months; no significant differences were found between the groups. However, an increase in median PFS was observed in patients who achieved a therapeutic concentration of mitotane. Moreover, the achievement of therapeutic mitotane concentrations was the only factor significantly associated with improved PFS (HR 0.44, p = 0.006). Significant unfavorable prognostic factors associated with lower OS were Ki-67 level in the primary tumor > 20 % (HR 10.5, p = 0.006) and more than 1 site of metastases (HR 3.82, p = 0.02).Conclusions. This study showed that the addition of mitotane to EDP chemotherapy does not improve the median PFS and OS in the total patient population, however, the achievement of therapeutic mitotane concentrations is significantly associated with improved progression-free survival.

Rituximab as First-Line and Maintenance Therapy for Patients With Indolent Non-Hodgkin’s Lymphoma

2002 ◽  
Vol 20 (20) ◽  
pp. 4261-4267 ◽  
Author(s):  
John D. Hainsworth ◽  
Sharlene Litchy ◽  
Howard A. Burris ◽  
Daniel C. Scullin ◽  
Steven W. Corso ◽  
...  
Keyword(s):  
Stable Disease ◽  
Systemic Therapy ◽  
Response Rate ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Hodgkin's Lymphoma ◽  
First Line ◽  
Free Survival ◽  
Non Hodgkin's Lymphoma

PURPOSE: To evaluate response to single-agent rituximab in patients with indolent non-Hodgkin’s lymphoma (NHL) and no previous systemic therapy, and the feasibility, toxicity, and efficacy of maintenance rituximab, administered at 6-month intervals, in patients with objective response or stable disease after first-line rituximab therapy. PATIENTS AND METHODS: Patients with indolent NHL (follicular or small lymphocytic subtypes) previously untreated with systemic therapy received rituximab 375 mg/m2 intravenously weekly for 4 weeks. Patients were restaged at week 6 for response; those with objective response or stable disease received maintenance rituximab courses (identical dose and schedule) at 6-month intervals. Maintenance was continued for a maximum of four rituximab courses or until progression. Between March 1998 and May 1999, 62 patients were entered onto this trial; minimum follow-up was 24 months. RESULTS: Sixty patients (97%) completed the first 4-week course of rituximab and were assessable for response. All have now completed rituximab therapy; 36 (58%) received four courses at 6-month intervals. The objective response rate at 6 weeks was 47%; 45% of patients had stable disease. With continued maintenance, final response rate increased to 73%, with 37% complete responses. Response was similar in patients with follicular versus small lymphocytic subtypes (76% v 70%, respectively). Median actuarial progression-free survival was 34 months. Two patients experienced grade 3/4 toxicity with the first dose; one patient was removed from treatment. No cumulative or additional toxicities were seen with maintenance courses. CONCLUSION: Rituximab is highly active and extremely well tolerated as first-line single-agent therapy for indolent NHL. First-line treatment with scheduled maintenance at 6-month intervals produces high overall and complete response rates and a longer progression-free survival (34 months) than has been reported with a standard 4-week treatment.

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