European Multicenter Study on Degradable Starch Microsphere TACE: The Digestible Way to Conquer HCC in Patients with High Tumor Burden

To evaluate the safety and efficacy of transarterial chemoembolization with degradable starch microspheres (DSM-TACE) for the treatment of hepatocellular carcinoma (HCC) with a high tumor burden ineligible for or failing other palliative therapies, 121 patients from three European centers were included. Kaplan–Meier analysis was used for median overall survival (OS) and time to progression (TTP, mRECIST criteria) in months with a 95% confidence interval (95% CI). Uni- (UVA) and multivariate (MVA) analyses were performed using the Cox Proportional Hazard Model. The median OS of the study cohort was 15.5 (13.3–18.7) months. The UVA identified HCC lesions ≤10 cm, unilobar involvement, lower Child–Pugh class and Barcelona Clinic Liver Cancer (BCLC) stage, absence of vascular invasion, and extrahepatic metastases as factors for prolonged survival. MVA confirmed lesions of ≤10 cm and unilobar disease as independent OS factors. Median TTP was 9.5 (7.6–10.3) months. The best response was achieved after a median of 3 (range: 1–6) treatments with CR/PR/SD/PD in 13.5%/44.5%/25.2%/16.8%, respectively. DSM-TACE was well tolerated with no major clinical adverse events and only limited major laboratory events. Preserved liver function was observed after repetitive DSM-TACE treatments. Repetitive DSM-TACE is a safe, well-tolerated and effective treatment option for HCC patients with high tumor burden ineligible or failing other palliative therapies.

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Predictive impact of the inflammation-based indices in uveal melanoma liver metastases treated with transarterial hepatic chemoperfusion

Radiology and Oncology ◽

10.2478/raon-2021-0027 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Johannes M. Ludwig ◽

Johannes Haubold ◽

Sebastian Bauer ◽

Heike Richly ◽

Jens T. Siveke ◽

...

Keyword(s):

Liver Metastases ◽

Uveal Melanoma ◽

Inflammatory Markers ◽

Tumor Burden ◽

Study Cohort ◽

Proportional Hazard ◽

Reactive Protein ◽

Cox Proportional Hazard ◽

Kaplan Meier ◽

Upper Level

Abstract Background The aim of the study was to evaluate pretreatment inflammatory markers as prognostic factors in patients with unresectable uveal melanoma liver metastases treated with transarterial hepatic chemoperfusion. Patients and methods 54 patients (44% male, median age: 61 years) were retrospectively assessed. A median of 3 (range: 1–11) treatment sessions were performed with melphalan (92%) or fotemustin (8%). Inflammatory indices were calculated as follows: neutrophils/nl to lymphocytes/nl ratio (NLR), systemic immune-inflammation index ([platelets/nl × neutrophils/nl]/[lymphocytes/nl]; SII), and platelets/nl to lymphocytes/nl ratio (PLR). The cut-off for dichotomization purposes was set at the median (inflammatory indices, hepatic tumor burden) or the upper level of normal. Kaplan Meier analysis was performed for median overall survival (OS) in months, and Cox proportional hazard model for uni(UVA) and multivariate (MVA) hazard ratio (HR, 95%CI) analyses were performed. Results Median OS of the study cohort was 7.7 (6.3–10.9) months. In UVA OS was prolonged for low C reactive protein (CRP) (13.5 vs. 5.2; p = 0.0005), low SII (10.8 vs. 5.6; p = 0.0005), low NLR (11.1 vs. 6.3; p = 0.0045), low aspartate aminotransferase (AST) (11.5 vs. 5.6; p = 0.015), alanine aminotransferases (ALT) (11.5 vs. 5.6; p = 0.01), and tumor burden ≦ 50% (8.2 vs. 4.8; p = 0.007). MVA confirmed low CRP (HR: 0.29, 0.11–0.7; p = 0.005), low SII (HR: 0.19, 0.11–0.7; p = 0.008), and low ALT (HR: 0.13, 0.02–0.63; p = 0.011) as independent predictors for prolonged OS. Patients with ≦ 1, 2, 3 elevated significant MVA-factors survived a median of 14.9, 7.7, and 3.9 months, respectively (p = 0.0001). Conclusions Pretreatment inflammatory markers (CRP, SII) and AST were independent prognostic survival markers in patients with uveal melanoma liver metastases treated with transarterial hepatic chemoperfusion. A combination of factors may help to identify patients potentially benefitting from treatment.

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Real world treatment patterns of first-line combination therapies among BRAF+ metastatic melanoma patients stratified by tumor burden.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.5_suppl.198 ◽

2018 ◽

Vol 36 (5_suppl) ◽

pp. 198-198

Author(s):

Sameer Ghate ◽

Jackson Tang ◽

Zhiyi Li ◽

Antonio Reis Nakasato

Keyword(s):

Brain Metastasis ◽

Metastatic Melanoma ◽

Real World ◽

Tumor Burden ◽

Treatment Patterns ◽

Discontinuation Rate ◽

First Line ◽

High Tumor Burden ◽

Kaplan Meier ◽

Measured Time

198 Background: For patients (pts) with metastatic melanoma (MM) and BRAF V600 mutation (BRAF+), options for first-line (1L) systemic combination therapy include immunotherapy (IO) or targeted therapy (TT). This study describes real world treatment patterns among BRAF+ MM pts treated with 1L ipilimumab+nivolumab (I+N) or dabrafenib+trametinib (D+T), stratified by tumor burden. Methods: A retrospective observational analysis used Flatiron Health’s electronic health record-derived database from Oct ’15 - Jul ’16. Pts were aged ≥18 years with a MM diagnosis, tested BRAF+ prior to therapy, and treated with ipilimumab+nivolumab (I+N) or dabrafenib+trametinib (D+T) as 1L therapy. Low tumor burden was defined as low/normal LDH (≤ 333 IU/L) and no brain metastasis. High tumor burden was defined as high LDH ( > 333 IU/L) or brain metastasis. Baseline characteristics and treatment patterns were descriptively assessed. Kaplan-Meier (KM) analysis measured time to discontinuation. Results: Among 76 BRAF+ pts, 38% (29) were treated with I+N as 1L, and 62% (47) were treated with D+T as 1L. Of these, 45% (13/29) of I+N vs. 32% (15/47) of D+T had low tumor burden, while 41% (12/29) of I+N vs. 49% (23/47) of D+T had high tumor burden. The two cohorts did not differ by age or gender. Treatment patterns are summarized below. Conclusions: Among pts with low tumor burden, I+N demonstrated shorter time to discontinuation and higher discontinuation rate relative to D+T. Treatment toxicity and progression was the main reason for discontinuation of I+N and D+T, respectively. Among pts with high tumor burden, I+N demonstrated longer time to discontinuation but higher discontinuation rate relative to D+T. Progression was the main reason for discontinuation of both I+N and D+T. [Table: see text]

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Clinical predictors of long-term response to capecitabine in metastatic breast cancer (MBC).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.1088 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 1088-1088

Author(s):

Deirdre Kelly ◽

Sasha M. Lupichuk ◽

Philippe L. Bedard ◽

Karen King ◽

David W. Cescon ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Metastatic Breast ◽

Study Cohort ◽

Clinical Predictors ◽

Kaplan Meier ◽

Best Response ◽

Metastatic Setting ◽

Term Response

1088 Background: Select patients (pts) with metastatic breast cancer (MBC) treated with capecitabine (cape) experience long-term disease control. We aimed to evaluate the clinical and biological predictors of long-term response. Methods: Pts receiving cape monotherapy for breast cancer from 01/2006 to 01/2016 at Princess Margaret Cancer Centre in Toronto, Canada (N = 352) or Alberta, Canada (N = 798) were identified through central pharmacy records. A median time-to-progression (MTTP) 3-fold higher (19.3 months) than those seen in published studies for patients treated with cape monotherapy at 1000mg/m2 was applied to select for pts with long-term response. MBC pts meeting these criteria were identified through chart review, with collection of clinical, pathological, and survival outcomes in addition to oncologist assessed (o) best response (eg: oCR, oPR, oSD) by radiology report review. Descriptive statistics, Kaplan-Meier and Cox-regressions were applied. Results: Overall, 41 (4%) pts met long-term response criteria. Median age of the study cohort was 62 (range 40-80), with 39% metastatic at diagnosis and 76% post-menopausal. At initiation of cape, a majority of pts were HR positive (85%), with an LDH < ULN (56%), and had bone (83%) or visceral (63%) metastases. Only 1 (2%) patient was HER2+. In the metastatic setting, most patients were chemotherapy-naive (83%) and had received 0-1 lines of hormonal therapy (61%). Median treatment duration with cape was 2.2 years (range 1.7-5.7) with 37% of pts having ≥40 cycles (range 22-94). Visceral (49%), bone (34%), and lymph nodes (24%) were the most common sites of progression, with 41% requiring 1 dose reduction and 27% requiring 2 dose reductions of cape. Overall response rate was 56% (oCR = 2%, oPR = 54%) with 44% having oSD as best response. Median follow-up was 6.8 years (95%CI: 5.5-8.2). Median PFS was 2.3 years (2.0-2.6), with a median OS of 3.8 years (2.9-4.6). 5 patients (12%) remained alive at data-cutoff, and 1 (2%) remained on treatment after 94 cycles of cape. Conclusions: Clinical features associated with long-term response on cape include HR positive, HER2 negative postmenopausal patients with bone predominant metastasis who have received 0-2 lines of prior hormone therapy and 0-1 lines of chemotherapy in the metastatic setting. This is the largest reported analysis of MBC patients with prolonged responses to cape. In the absence of randomized controlled trials; real-world evidence could aid clinicians in the optimal patient selection for treatment with cape.

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A Case of Duodenal Neuroendocrine Carcinoma Treated with Amrubicin as Second-line Chemotherapy

Journal of Gastrointestinal and Liver Diseases ◽

10.15403/jgld.2014.1121.243.ino ◽

2015 ◽

Vol 24 (3) ◽

pp. 379-382

Author(s):

Tadahisa Inoue ◽

Hitoshi Sano ◽

Takashi Mizushima ◽

Hirotada Nishie ◽

Hiroyasu Iwasaki ◽

...

Keyword(s):

Neuroendocrine Carcinoma ◽

Distant Metastases ◽

Salvage Chemotherapy ◽

Second Line ◽

Effective Treatment Option ◽

Second Line Chemotherapy ◽

Best Response ◽

Long Term Effect ◽

Line Chemotherapy

We present the case of a Japanese man in his 60s with duodenal neuroendocrine carcinoma with distant metastases. Chemotherapy with irinotecan plus cisplatin was initiated as a first-line regimen. However, disease progression was observed after only two cycles. Therefore, amrubicin was administered as a second-line chemotherapy. The patient showed a long-term effect of amrubicin therapy, and the best response was a partial response after seven cycles. For duodenal neuroendocrine carcinoma, amrubicin therapy can be considered an effective treatment option as salvage chemotherapy.

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Impact of pretreatment anemia on upfront abiraterone acetate therapy for metastatic hormone-sensitive prostate cancer: a multicenter retrospective study

BMC Cancer ◽

10.1186/s12885-021-08206-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Teppei Okamoto ◽

Daisuke Noro ◽

Shingo Hatakeyama ◽

Shintaro Narita ◽

Koji Mitsuzuka ◽

...

Keyword(s):

Prostate Cancer ◽

Prognostic Factor ◽

Abiraterone Acetate ◽

Tumor Burden ◽

Hazard Ratio ◽

Historical Cohort ◽

High Tumor Burden ◽

Significant Difference ◽

Hormone Sensitive ◽

The Impact

Abstract Background Anemia has been a known prognostic factor in metastatic hormone-sensitive prostate cancer (mHSPC). We therefore examined the effect of anemia on the efficacy of upfront abiraterone acetate (ABI) in patients with mHSPC. Methods We retrospectively evaluated 66 mHSPC patients with high tumor burden who received upfront ABI between 2018 and 2020 (upfront ABI group). We divided these patients into two groups: the anemia-ABI group (hemoglobin < 13.0 g/dL, n = 20) and the non-anemia-ABI group (n = 46). The primary objective was to examine the impact of anemia on the progression-free survival (PFS; clinical progression or PC death before development of castration resistant PC) of patients in the upfront ABI group. Secondary objectives included an evaluation of the prognostic significance of upfront ABI and a comparison with a historical cohort (131 mHSPC patients with high tumor burden who received androgen deprivation therapy (ADT/complete androgen blockade [CAB] group) between 2014 and 2019). Results We found that the anemia-ABI group had a significantly shorter PFS than the non-anemia-ABI group. A multivariate Cox regression analysis showed that anemia was an independent prognostic factor of PFS in the upfront ABI group (hazard ratio, 4.66; P = 0.014). Patients in the non-anemia-ABI group were determined to have a significantly longer PFS than those in the non-anemia-ADT/CAB group (n = 68) (P < 0.001). However, no significant difference was observed in the PFS between patients in the anemia-ABI and the anemia-ADT/CAB groups (n = 63). Multivariate analyses showed that upfront ABI could significantly prolong the PFS of patients without anemia (hazard ratio, 0.17; P < 0.001), whereas ABI did not prolong the PFS of patients with anemia. Conclusion Pretreatment anemia was a prognostic factor among mHSPC patients who received upfront ABI. Although the upfront ABI significantly improved the PFS of mHSPC patients without anemia, its efficacy in patients with anemia might be limited.

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The natural history of Canavan disease: 23 new cases and comparison with patients from literature

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-020-01659-3 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Annette Bley ◽

Jonas Denecke ◽

Alfried Kohlschütter ◽

Gerhard Schön ◽

Sandra Hischke ◽

...

Keyword(s):

Severity Score ◽

Canavan Disease ◽

Psychomotor Development ◽

Rank Test ◽

First Year ◽

Study Cohort ◽

Pooled Data ◽

Kaplan Meier ◽

History Of ◽

First Year Of Life

Abstract Background Canavan disease (CD, MIM # 271900) is a rare and devastating leukodystrophy of early childhood. To identify clinical features that could serve as endpoints for treatment trials, the clinical course of CD was studied retrospectively and prospectively in 23 CD patients. Results were compared with data of CD patients reported in three prior large series. Kaplan Meier survival analysis including log rank test was performed for pooled data of 82 CD patients (study cohort and literature patients). Results Onset of symptoms was between 0 and 6 months. Psychomotor development of patients was limited to abilities that are usually gained within the first year of life. Macrocephaly became apparent between 4 and 18 months of age. Seizure frequency was highest towards the end of the first decade. Ethnic background was more diverse than in studies previously reported. A CD severity score with assessment of 11 symptoms and abilities was developed. Conclusions Early hallmarks of CD are severe psychomotor disability and macrocephaly that develop within the first 18 months of life. While rare in the first year of life, seizures increase in frequency over time in most patients. CD occurs more frequently outside Ashkenazi Jewish communities than previously reported. Concordance of phenotypes between siblings but not patients with identical ASPA mutations suggest the influence of yet unknown modifiers. A CD severity score may allow for assessment of CD disease severity both retrospectively and prospectively.

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The sentinel node invasion level (SNIL) as a prognostic parameter in melanoma

Modern Pathology ◽

10.1038/s41379-021-00835-5 ◽

2021 ◽

Author(s):

Lutz Kretschmer ◽

Christina Mitteldorf ◽

Simin Hellriegel ◽

Andreas Leha ◽

Alexander Fichtner ◽

...

Keyword(s):

Lymph Node ◽

Prognostic Significance ◽

Tumor Burden ◽

Recurrence Rates ◽

Cox Models ◽

Nodal Basin ◽

Lymph Vessels ◽

Kaplan Meier ◽

Metastasis Patterns ◽

Transverse Sinuses

AbstractSentinel lymph node (SN) tumor burden is becoming increasingly important and is likely to be included in future N classifications in melanoma. Our aim was to investigate the prognostic significance of melanoma infiltration of various anatomically defined lymph node substructures. This retrospective cohort study included 1250 consecutive patients with SN biopsy. The pathology protocol required description of metastatic infiltration of each of the following lymph node substructures: intracapsular lymph vessels, subcapsular and transverse sinuses, cortex, paracortex, medulla, and capsule. Within the SN with the highest tumor burden, the SN invasion level (SNIL) was defined as follows: SNIL 1 = melanoma cells confined to intracapsular lymph vessels, subcapsular or transverse sinuses; SNIL 2 = melanoma infiltrating the cortex or paracortex; SNIL 3 = melanoma infiltrating the medulla or capsule. We classified 338 SN-positive patients according to the non-metric SNIL. Using Kaplan–Meier estimates and Cox models, recurrence-free survival (RFS), melanoma-specific survival (MSS) and nodal basin recurrence rates were analyzed. The median follow-up time was 75 months. The SNIL divided the SN-positive population into three groups with significantly different RFS, MSS, and nodal basin recurrence probabilities. The MSS of patients with SNIL 1 was virtually identical to that of SN-negative patients, whereas outgrowth of the metastasis from the parenchyma into the fibrous capsule or the medulla of the lymph node indicated a very poor prognosis. Thus, the SNIL may help to better assess the benefit-risk ratio of adjuvant therapies in patients with different SN metastasis patterns.

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Temozolomide in Malignant Gliomas of Childhood: A United Kingdom Children’s Cancer Study Group and French Society for Pediatric Oncology Intergroup Study

Journal of Clinical Oncology ◽

10.1200/jco.2002.08.141 ◽

2002 ◽

Vol 20 (24) ◽

pp. 4684-4691 ◽

Cited By ~ 138

Author(s):

L. S. Lashford ◽

P. Thiesse ◽

A. Jouvet ◽

T. Jaspan ◽

D. Couanet ◽

...

Keyword(s):

Response Rate ◽

Objective Response ◽

Malignant Gliomas ◽

High Grade Glioma ◽

Study Cohort ◽

High Grade ◽

French Society ◽

Significant Treatment ◽

Best Response ◽

Daily Schedule

PURPOSE: To determine the response rate of the malignant gliomas of childhood to an oral, daily schedule of temozolomide. PATIENTS AND METHODS: A multicenter, phase II evaluation of an oral, daily schedule of temozolomide (200 mg/m2 on 5 consecutive days) was undertaken in children with relapsed or progressive, biopsy-proven, high-grade glioma (arm A) and progressive, diffuse, intrinsic brainstem glioma (arm B). Evidence of activity was defined by radiologic evidence of a sustained reduction in tumor size on serial magnetic resonance imaging scans. RESULTS: Fifty-five patients were recruited (34 to arm A and 21 to arm B) and received 215 cycles of chemotherapy. Grade 3/4 thrombocytopenia was the most frequent toxic event (7% of cycles). Prolonged myelosuppression resulted in significant treatment delays and dose reductions (17% and 22% of cycles, respectively). Two toxic deaths were documented and were related to myelosuppression and sepsis in one patient and pneumonia in a second. The overall (best) response rate was 12% for arm A (95% confidence interval [CI], 3 to 28 in the study cohort, and 2 to 31 for eligible patients) and 5% and 6%, respectively, for arm B (95% CI, 0 to 26 in the study cohort, and 0 to 27 for eligible patients). Stabilization of disease was also documented and was most noteworthy for brainstem gliomas, where two patients achieved both radiologic static disease and discontinued steroid medication. CONCLUSION: Despite moderate toxicity, objective response rates to temozolomide have been low, indicating that temozolomide has minimal activity in the high-grade gliomas of childhood.

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Overall survival benefit from tebentafusp in patients with best response of progressive disease.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.9509 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 9509-9509

Author(s):

Anthony M. Joshua ◽

Jean-Francois Baurain ◽

Sophie Piperno-Neumann ◽

Paul Nathan ◽

Jessica Cecile Hassel ◽

...

Keyword(s):

Overall Survival ◽

Safety Profile ◽

Progressive Disease ◽

Analysis Data ◽

Cell Receptor ◽

Kaplan Meier ◽

Immortal Time Bias ◽

Best Response ◽

Overall Survival Benefit

9509 Background: Tebentafusp (tebe) is the first T cell receptor (TCR) therapeutic to demonstrate an overall survival (OS) benefit in a randomized Phase 3 (Ph3) study [ NCT03070392 ]. In Ph2, 42% of pts with best overall response (BOR) of progressive disease (PD) survived > 1 year (yr), suggesting RECIST-based radiographic assessments underestimate OS benefit of tebe. Here we analyzed OS in the Ph3 study in a cohort of pts with BOR of PD by comparing tebe to the control arm of investigator’s choice (IC). Methods: 378 pts were randomized in a 2:1 ratio to tebe vs. IC. BOR was assessed by investigators using RECIST v1.1. Treatment beyond first disease progression (TBP) was permitted for both arms. On the IC arm, only patients receiving pembrolizumab (pembro) continued with TBP and were included in the TBP-related analyses. No crossover to tebe was permitted; investigators were free to choose subsequent therapy. This analysis was conducted on the first interim analysis (data extracted Nov-2020). Kaplan-Meier estimates of OS were based on Day 100 landmark to eliminate immortal time bias and to capture majority of the PDs. Results: By Day 100, PD as BOR occurred in 52% (130/252) of tebe pts (PD-tebe) vs. 60% (76/126) of IC pts (PD-IC). Key baseline characteristics including lactate dehydrogenase, alkaline phosphatase, ECOG performance, age, and sex were similar between PD-tebe vs PD-IC. The proportion of pts with PD due to progression of target lesions (TL), non-TL, or new lesions were also similar between the two groups. More pts received TBP among PD-tebe 53% (69/130) vs PD-pembro 16% (10/61). Median duration of TBP was longer for PD-tebe (7 weeks) vs PD-Pembro (3 weeks). The safety profile of PD-tebe pts during TBP was similar to all tebe-treated pts. OS was superior for PD-tebe vs PD-IC, HR = 0.41 (95%CI 0.25-0.66), even when considering key baseline covariates. While some pts had regression of TL despite diagnosis of PD ( < 10% of pts), the OS benefit remained even when limited to pts with best change of tumor growth of TL, HR 0.46 (0.29, 0.73). 58% (75/130) PD-tebe and 52% (40/76) PD-IC pts received subsequent therapies. In a landmark OS analysis of these pts beginning on 1st day of subsequent therapy, prior tebe was associated with better OS vs. prior IC, HR 0.59 (95%CI 0.36-0.96). Conclusions: Tebe is the first TCR therapeutic to demonstrate an OS benefit in a solid tumor. Surprisingly, a strong OS benefit from tebe is observed even in pts with BOR of PD, suggesting that RECIST-based radiographic assessments do not capture the complete benefit from tebe. The safety profile of tebe during TBP was consistent with that for long-term tebe treatment. Clinical trial information: NCT03070392.

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Obinutuzumab plus lenalidomide (GALEN) in advanced, previously untreated follicular lymphoma in need of systemic therapy

Blood ◽

10.1182/blood.2021013526 ◽

2021 ◽

Author(s):

Emmanuel Bachy ◽

Roch Houot ◽

Pierre Feugier ◽

Krimo Bouabdallah ◽

Reda Bouabdallah ◽

...

Keyword(s):

Follicular Lymphoma ◽

Safety Profile ◽

Response Rate ◽

Metabolic Response ◽

Complete Response ◽

Tumor Burden ◽

Common Adverse Event ◽

Induction Treatment ◽

High Tumor Burden ◽

Grade 3

Obinutuzumab and lenalidomide (GALEN) is an active immunomodulatory combination with a manageable safety profile in multiple types of lymphoma. We report efficacy and safety results for the phase 2 GALEN study in previously-untreated patients with advanced follicular lymphoma (FL). Eligible patients aged ≥ 18 years had ECOG PS ≤ 2, high-tumor burden, grade 1-3a FL. Induction treatment was obinutuzumab (1000 mg IV, days 8/15/22, cycle 1; day 1, cycles 2-6) plus lenalidomide (20 mg/day, days 1-21, cycle 1; days 2-22, cycles 2-6) for 6 cycles. Maintenance included obinutuzumab (1000 mg every 2 cycles) plus lenalidomide (10 mg, days 2-22) for ≤ 12 cycles (year 1) followed by obinutuzumab (1000 mg every 56 days) for 6 cycles (year 2). The primary endpoint was complete response rate (CRR) after induction per IWG 1999 criteria. From October 2015 to February 2017, 100 patients were enrolled. CRR after induction was 47% and overall response rate (ORR) 92%. Post-hoc analyses per 2014 Lugano classification including patients with missing bone marrow assessments identified an additional 13 patients fulfilling CRR criteria, resulting in a complete metabolic response of 80% and ORR of 94%. At a median follow-up of 3.7 years, 3-year progression-free and overall survival were 82% and 94%, respectively. The most common adverse event was neutropenia (48% any-grade; 47% grade ≥ 3) but only 2% of patients presented febrile neutropenia; others were mainly grade ≤ 2. No other specific grade ≥3 toxicity occurred at a frequency higher than 3%. Overall, these results demonstrated promising clinical efficacy for the chemo-free backbone obinutuzumab and lenalidomide in previously untreated, high tumor burden FL patients. Except for neutropenia, the safety profile of the combination is remarkable. The study was registered with ClinicalTrials.gov, number NCT01582776

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