Abstract: Introduction: The CLL2-BCG trial is a prospective, open-label, multicenter phase-II study based on the "sequential triple-T" (tailored, targeted, total eradication of CLL) concept proposed earlier [Hallek M., Blood 2013; 122(23): 3723-34]. This concept consists of sequentially applied combinations of targeted agents and aims for achieving undetectable minimal residual disease (MRD). It uses a sequential application of bendamustine (Ben) for debulking, followed by obinutuzumab (Obi) plus idelalisib (Ide) as induction and maintenance therapy for an all-comer population of physically fit and unfit, treatment-naïve (t-n) and relapsed/refractory (r/r) CLL patients (pts) irrespective of high-risk genetic markers. Methods: Pts with an absolute lymphocyte count ≥ 25.000/µl and/or lymph nodes ≥ 5 cm were to receive 2 cycles of Ben as debulking (70 mg/m² d1 & 2 q28 d), unless contraindicated. In the induction phase Obi 1000 mg was administered on d 1, 8 and 15 of cycle 1 and d1 of cycles 2-6; Ide was added in cycle 2 (150 mg twice daily). In the maintenance phase, daily dosing of Ide was continued and Obi was administered every 3 months until achieving a MRD-negative complete response or for up to 24 months. The primary endpoint was the overall response rate (ORR) at the end of induction therapy, secondary endpoints included MRD assessment, safety and survival. Due to an increased incidence of opportunistic infections in other Ide trials, amendment 2 in March 2016 limited the recruitment to r/r CLL pts with high-risk features such as presence of a deletion 17p/TP53 mutation and/or ineligibility for ibrutinib treatment (refractoriness, intolerance or contraindications). Slow enrolment led to recruitment stop in September 2019. Results: Between May 2015 and September 2019, 48 pts were enrolled. Sixteen pts were t-n and 32 had r/r CLL with a median of 2 prior lines (range: 1-10); most common were BR and FCR, 6 pts each had received ibrutinib and venetoclax containing therapies. Median age was 66 (range 41-83) years, median CIRS score was 2 (0-13). Twenty-three pts (48%) were defined unfit by a CIRS score & gt;6 (7 pts) and/or an impaired renal function with a Creatinine Clearance & lt;70ml/Min (19 pts); 39 pts were male (81%). Nineteen pts (40%) had a del(17p) and/or TP53 mutation; 33 (70%) an unmutated IGHV status and 15 pts (42%) a complex karyotype, 36 pts (80%) had a high or very high CLL-IPI. Thirty-eight patients (79%, 16 t-n and 22r/r) received Ben debulking. However, 8 pts never started the induction phase due to protocol amendment 2. Forty pts (10 t-n, 30 r/r) received induction treatment (FAS [full analysis set]), 33 completed the full 6 cycles (PP [per protocol] collective). Twenty-seven (7 t-n, 20 r/r) continued in a maintenance phase. At the end of induction, 32 of 40 pts (FAS) and 28 of 33 pts with 6 induction cycles (PP) responded (ORR 80% and 85%, respectively); undetectable MRD levels ( & lt;10-4) by 4-color flow were achieved in 9 pts (23% and 27%, respectively) [Table 1]. Median progression-free survival was 44 months in t-n and 33 months in r/r CLL pts. Median overall survival was not reached for the t-n and 46 months in r/r pts; nine pts died, seven due to infections (two sepsis, including one in the context of severe enterocolitis, one pneumocystis jirovecii pneumonia and one influenza pneumonia, the other three after disease progression/start of subsequent treatment were considered unrelated to stud treatment), one cardiac arrest and one due to Richter´s transformation. As of June 8th 2020, 603 adverse events (AEs) were reported in the entire cohort; 313 (52%) were related to study drug and 127 (21%) were serious adverse events. 286 (47%) occurred in the induction treatment (see table 1). Of these, 69 (24%) were CTC grade 3 and 18 (6%) CTC grade 4, 4 had a fatal outcome. Most common AEs in the induction were infusion-related reactions, neutropenia, thrombocytopenia, anemia, nasopharyngitis, headache, and fatigue [Table 2]. Summary/Conclusion: Sequential treatment with Ben debulking, followed by Obi and Ide induction and maintenance achieved responses and even undetectable MRD levels in CLL patients with high-risk disease and extensive prior therapy. However, the study also confirmed the known toxicities of Ide. In light of the current, alternative therapeutic options, the BCG regimen reported here should be used with caution, but represents an alternative treatment option if ibrutinib and venetoclax have failed. Disclosures Cramer: Gilead: Other: travel support, Research Funding; F. Hoffmann-LaRoche: Honoraria, Other: travel support, Research Funding; Acerta: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Consultancy, Honoraria, Other: travel support, Research Funding; Beigene: Research Funding; AbbVie: Honoraria, Other: travel support; Novartis: Consultancy, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Other: travel support, Research Funding. Von Tresckow:Celgene: Other: travel grants; AbbVie: Honoraria; Janssen-Cilag: Honoraria, Other: travel grants, Research Funding; F. Hoffmann-LaRoche: Honoraria, Other: travel grants, Research Funding. Fink:AbbVie: Other: travel grants; Janssen: Honoraria; Celgene: Research Funding. Tausch:Janssen-Cilag: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding. Knauf:Janssen-Cilag: Honoraria; AbbVie: Consultancy, Honoraria; AMGEN: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Mundipharma: Honoraria. Al-Sawaf:BeiGene: Research Funding; AbbVie: Consultancy, Honoraria, Other: personal fees, Research Funding; Roche: Consultancy, Honoraria, Other: personal fees, Research Funding; Gilead: Consultancy, Honoraria, Other: personal fees; Janssen: Consultancy, Honoraria, Other: personal fees, Research Funding; AstraZeneca: Consultancy, Honoraria, Other: personal fees. Langerbeins:AbbVie: Honoraria, Other: travel grants, Research Funding; F. Hoffmann-LaRoche: Honoraria, Other: travel grants, Research Funding; Janssen-Cilag: Honoraria, Other: travel grants, Research Funding; Mundipharma: Honoraria, Other: travel grants, Research Funding. Fischer:F. Hoffmann-La Roche: Honoraria, Other: travel grants; AbbVie: Honoraria. Kreuzer:Hoffmann-La Roche: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Honoraria, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Research Funding; Mundipharma: Consultancy, Honoraria, Research Funding. Ritgen:Gilead: Other: travel grants; BMS: Consultancy, Honoraria, Other: travel grants; F. Hoffman-La Roche: Consultancy, Honoraria, Other: travel grants, Research Funding; Pfizer: Consultancy, Honoraria. Kneba:AbbVie: Consultancy, Honoraria, Other: travel support, Research Funding; F. Hoffmann-LaRoche: Consultancy, Honoraria, Other: travel support, Research Funding; Gilead: Consultancy, Honoraria, Other: travel support, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Other: travel support, Research Funding; Mundipharma: Consultancy, Honoraria, Other: travel support, Research Funding. Wendtner:Mundipharma: Consultancy, Honoraria, Other: travel support, Research Funding; Pharmacyclics: Consultancy, Honoraria, Other: travel support, Research Funding; AbbVie: Consultancy, Honoraria, Other: travel support, Research Funding; Gilead: Consultancy, Honoraria, Other: travel support, Research Funding; Hoffmann-LaRoche: Consultancy, Honoraria, Other: travel support, Research Funding; Genentech: Consultancy, Honoraria, Other: travel support, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Other: travel support, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Other: travel support, Research Funding. Stilgenbauer:Pharmacyclics: Consultancy, Honoraria, Other, Research Funding; Novartis: Consultancy, Honoraria, Other, Research Funding; Mundipharma: Consultancy, Honoraria, Other, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Other: travel support, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Other: travel support, Research Funding; Gilead: Consultancy, Honoraria, Other: travel support, Research Funding; Genzyme: Consultancy, Honoraria, Other: travel support, Research Funding; Genentech: Consultancy, Honoraria, Other: travel support, Research Funding; F. Hoffmann-LaRoche: Consultancy, Honoraria, Other: travel support, Research Funding; Celgene: Consultancy, Honoraria, Other: travel support, Research Funding; Boehringer-Ingelheim: Consultancy, Honoraria, Other: travel support, Research Funding; Amgen: Consultancy, Honoraria, Other: travel support, Research Funding; AbbVie: Consultancy, Honoraria, Other: travel support, Research Funding. Eichhorst:Janssen-Cilag: Consultancy, Honoraria, Other: travel support, Research Funding; Celgene: Consultancy, Honoraria, Other: travel support, Research Funding; Novartis: Consultancy, Honoraria, Other: travel support, Research Funding; ArQule: Consultancy, Honoraria, Other: travel support, Research Funding; BeiGene: Consultancy, Honoraria, Other: travel support, Research Funding; Gilead: Consultancy, Honoraria, Other: travel support, Research Funding; AstraZeneca: Consultancy, Honoraria, Other: travel support, Research Funding; Oxford Biomedica: Consultancy, Honoraria, Other: travel support, Research Funding; F. Hoffmann-LaRoche: Consultancy, Honoraria, Other: travel support, Research Funding; AbbVie: Consultancy, Honoraria, Other: travel support, Research Funding. Hallek:F. Hoffmann-LaRoche: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Honoraria, Research Funding; Mundipharma: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding.

Abstract: INTRODUCTION Chronic lymphocytic leukemia (CLL) is frequently associated with an impaired humoral and cellular immunity. On a global scale chemoimmunotherapy (CIT) has remained one of the most frequently used treatment option. Thus, patients (pts) may experience further cytopenia, particularly treatment-related neutropenia, increasing the risk of infections. In order to better characterize incidence, characteristics and outcomes of infections during and after therapy, a pooled analysis of phase II and III German CLL Study Group trials was performed. METHODS Data of first line pts from 5 clinical trials (CLL7, pts treated with fludarabine, cyclophosphamide, rituximab [FCR]; CLL8, FC vs FCR; CLL10, FCR vs bendamustine-rituximab [BR] ; CLL11, chlorambucil [CLB] vs CLB-R vs CLB-Obinutuzumab [CLB-Ob] and CLL2M, BR) were analyzed. Clinical, laboratory, genetic and event-related data were pooled. Infections defined as severe (CTC grade 3-5) from initiation of therapy until 4 weeks after completion of study treatment were considered related. Due to varying reporting periods for infections of the respective trials later events of infections were not included. Kaplan-Meier curves for landmark overall survival (OS) from completion of study treatment plus 4 weeks were plotted and compared by non-stratified log-rank test. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox proportional-hazard regression modelling. RESULTS Data from 2,291 pts receiving at least one dose of CIT were pooled. Median observation time was 71.7 months, ranging between 43.7 months (CLL2M) and 81.0 months (CLL10). Seven-hundred and twenty-seven pts received FCR, 396 pts FC, 395 pts BR, 116 pts CLB, 326 pts CLB-R and 331 pts CLB-Ob. Overall, 274 severe grad 3/4/5 infections were reported in 229 pts (10.0% of 2,291 pts). Of those 189 pts (82.5%) had max. grade 3 infections, 22 (9.6%) pts had grade 4 infections and 18 (7.9%) pts died due to infectious complications. Median time to severe infection from start of treatment was 1.8 months (IQR 0.9-3.6), with a median number of infectious episodes per patient of 1 (range 1-4). Thirty-one (13.5%) of 229 pts had bacterial infections, 35 (15.3%) viral infections, 5 (2.2%) fungal infections and 172 (75.1%) unspecified infections. Higher grade (i.e. ≥ CTC grade 3) leukopenia and/or neutropenia was reported in 121 (52.8%) pts with severe infections. Eighty-eight (12.1%) of FCR treated pts had severe infections, followed by BR 45 (11.4%), CLB 12 (10.3%), FC 35 (8.8%), CLB-Ob 25 (7.6%) and CLB-R 24 (7.4%). Median age was 64 years in the entire cohort; no differences between pts with and without infections were observed with regards to age, sex, ECOG or creatinine clearance. Molecular and cytogenetic characteristics (deletion 17p, deletion 11q, trisomy 12) and IGHV status were similarly distributed between both groups. Median neutrophil count at enrolment was 4.4x10-9/l in both groups, respectively. Prior to therapy, levels of immunoglobulin were comparable between pts with and without infections (median IgG 7.0 vs 7.5 g/L, IgM 0.3 g/L vs 0.3 g/L). Also, pts with at least one episode of ≥ CTC grade 3 leukopenia/neutropenia had comparable rates of severe infections to pts without higher grade leukopenia/neutropenia (147 [53.6%] vs 127 [46.4%] pts). No differences were observed between pts with or without infections regarding the response to first line treatment (183 pts [79.9%] with complete response or partial response to treatment vs 1715 pts [83.2%] ) as well as the rate of undetectable minimal residual disease levels (50 [21.8%] vs 477 [23.1%] ). Overall survival from 4 weeks after completion of study treatment was significantly shorter in pts with severe infections compared to pts without severe infections (median 73.7 months vs 97.3 months, HR 1.503, 95% CI 1.217-1.856, p & lt; 0.001). CONCLUSION This analysis confirms that prognosis of CLL pts who received first line treatment with (immuno)chemotherapy is influenced by severe infections. This risk does not correlate with the explored cyto- or molecular genetic risk factors, nor with response to treatment, pre-therapeutic levels of immunoglobulins or occurrence of higher grade neutropenia. Pts who experience severe infections have a significantly shorter overall survival compared to pts without severe infections. Due to their vulnerability, careful management of infectious complications in CLL pts is warranted. Figure 1 Disclosures Al-Sawaf: AbbVie: Consultancy, Honoraria, Other: personal fees, Research Funding; Janssen: Consultancy, Honoraria, Other: personal fees, Research Funding; AstraZeneca: Consultancy, Honoraria, Other: personal fees; BeiGene: Research Funding; Roche: Consultancy, Honoraria, Other: personal fees, Research Funding; Gilead: Consultancy, Honoraria, Other: personal fees. Fink:Janssen: Honoraria; Celgene: Research Funding; AbbVie: Other: travel grants. Cramer:F. Hoffmann-LaRoche: Honoraria, Other: travel support, Research Funding; AstraZeneca: Consultancy, Honoraria, Other: travel support, Research Funding; Acerta: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Other: travel support, Research Funding; Beigene: Research Funding; Novartis: Consultancy, Research Funding; Gilead: Other: travel support, Research Funding; AbbVie: Honoraria, Other: travel support. Herling:Roche: Other: Travel support, Research Funding. Von Tresckow:Janssen-Cilag: Honoraria, Other: travel grants, Research Funding; Celgene: Other: travel grants; F. Hoffmann-LaRoche: Honoraria, Other: travel grants, Research Funding; AbbVie: Honoraria. Böttcher:Novartis: Honoraria; AbbVie: Honoraria, Research Funding; Celgene: Research Funding; Janssen: Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding. Dreyling:Astra Zeneca: Consultancy; Abbvie: Research Funding; Roche: Consultancy, Research Funding, Speakers Bureau; Bayer: Consultancy, Speakers Bureau; Beigene: Consultancy; Gilead: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy; Celgene: Consultancy, Research Funding, Speakers Bureau. Jaeger:F. Hoffmann-La Roche: Honoraria, Research Funding; Gilead: Honoraria, Research Funding; BMS/Celgene: Consultancy, Honoraria, Research Funding; Infinity: Honoraria; Takeda: Honoraria; Amgen: Honoraria; Karyopharm: Honoraria; CDR Life AG: Consultancy, Research Funding; Miltenyi: Consultancy, Honoraria; True North: Honoraria, Research Funding; AbbVie: Honoraria; Novartis: Consultancy, Honoraria, Research Funding. Gregor:Roche: Honoraria; Mundipharma: Honoraria; AbbVie: Honoraria; Amgen: Honoraria; Celgene: Honoraria; Janssen: Honoraria; Pfizer: Honoraria. Ritgen:Pfizer: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Other: travel grants; F. Hoffman-La Roche: Consultancy, Honoraria, Other: travel grants, Research Funding; Gilead: Other: travel grants. Dürig:Janssen: Consultancy; AbbVie: Consultancy; Celgene: Consultancy. Tausch:AbbVie: Consultancy, Honoraria, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding. Stilgenbauer:GlaxoSmithKline: Consultancy, Honoraria, Other: travel support, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Other: travel support, Research Funding; Mundipharma: Consultancy, Honoraria, Other, Research Funding; Gilead: Consultancy, Honoraria, Other: travel support, Research Funding; Genzyme: Consultancy, Honoraria, Other: travel support, Research Funding; Novartis: Consultancy, Honoraria, Other, Research Funding; Pharmacyclics: Consultancy, Honoraria, Other, Research Funding; Genentech: Consultancy, Honoraria, Other: travel support, Research Funding; F. Hoffmann-LaRoche: Consultancy, Honoraria, Other: travel support, Research Funding; Celgene: Consultancy, Honoraria, Other: travel support, Research Funding; Boehringer-Ingelheim: Consultancy, Honoraria, Other: travel support, Research Funding; Amgen: Consultancy, Honoraria, Other: travel support, Research Funding; AbbVie: Consultancy, Honoraria, Other: travel support, Research Funding. Wendtner:Janssen-Cilag: Consultancy, Honoraria, Other: travel support, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Other: travel support, Research Funding; Gilead: Consultancy, Honoraria, Other: travel support, Research Funding; Genentech: Consultancy, Honoraria, Other: travel support, Research Funding; Hoffmann-LaRoche: Consultancy, Honoraria, Other: travel support, Research Funding; AbbVie: Consultancy, Honoraria, Other: travel support, Research Funding; Mundipharma: Consultancy, Honoraria, Other: travel support, Research Funding; Pharmacyclics: Consultancy, Honoraria, Other: travel support, Research Funding. Fischer:F. Hoffmann-La Roche: Honoraria, Other: travel grants; AbbVie: Honoraria. Goede:AbbVie: Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-LaRoche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grants; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grants; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees. Hallek:F. Hoffmann-LaRoche: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Mundipharma: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Honoraria, Research Funding. Eichhorst:Oxford Biomedica: Consultancy, Honoraria, Other: travel support, Research Funding; AstraZeneca: Consultancy, Honoraria, Other: travel support, Research Funding; Gilead: Consultancy, Honoraria, Other: travel support, Research Funding; BeiGene: Consultancy, Honoraria, Other: travel support, Research Funding; ArQule: Consultancy, Honoraria, Other: travel support, Research Funding; Novartis: Consultancy, Honoraria, Other: travel support, Research Funding; Celgene: Consultancy, Honoraria, Other: travel support, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Other: travel support, Research Funding; AbbVie: Consultancy, Honoraria, Other: travel support, Research Funding; F. Hoffmann-LaRoche: Consultancy, Honoraria, Other: travel support, Research Funding. Langerbeins:AbbVie: Honoraria, Other: travel grants, Research Funding; F. Hoffmann-LaRoche: Honoraria, Other: travel grants, Research Funding; Janssen-Cilag: Honoraria, Other: travel grants, Research Funding; Mundipharma: Honoraria, Other: travel grants, Research Funding.

Abstract: Introduction: The GCLLSG has demonstrated the efficacy of a sequential therapy with bendamustine followed by obinutuzumab (or GA101; G) and ibrutinib (I) according to a "sequential triple-T" concept [Hallek M., Blood 2013] using a tailored and targeted treatment aiming at total eradication of minimal residual disease (MRD) in CLL [von Tresckow J, Leukemia 2019] . Here we present the results of the final analysis of the CLL2-BIG trial after the end of maintenance therapy. Methods: This phase-II trial investigated the efficacy and safety of a novel regimen for physically fit and unfit CLL patients (pts) requiring treatment, irrespective of high-risk genetics. 62 pts were to be recruited according to a predefined allocation for the two strata of first-line (1L) and relapse/refractory (RR) treatment. Six cycles of induction therapy with G and I were administered followed by maintenance therapy with continuous I and G every three months until achievement of an MRD-negative complete remission or up to 24 months. Pts with an absolute lymphocyte count ≥ 25.000/µl and/or lymph nodes ≥ 5cm were scheduled to receive two cycles of bendamustine before start of induction. The primary endpoint was the overall response rate 3 months after the start of last induction cycle administered; secondary endpoints included the best response rate, MRD evaluations as well as survival and safety parameters (graded per the NCI CTCAE v.4 criteria). Results: 66 pts were enrolled. Five pts completed less than two cycles of induction therapy and were therefore excluded from the full analysis set as defined by study protocol. Patient characteristics are shown in Table 1. Of note, half of the pts had received prior therapies and two thirds had a high/very-high CLL-IPI. At the end of induction, ORR was 100% and 29 pts (47.5%) achieved MRD-negativity ( 〈 10-4 by 4-color-flow cytometry) in peripheral blood (PB), as previously published. 59 of 61 pts (96.7%) started maintenance therapy. Response is shown in Figure 1 and was improved in 16 pts, with 6 pts (9.8%) achieving a complete remission (CR) or CR with incomplete recovery of the bone marrow (CRi) and 55 pts (90.2%) a PR by iwCLL criteria, including 54.1% patients who were lacking a bone marrow biopsy or CT scan but fulfilled all other criteria for CR/CRi (clinical CR). 42 pts (71.2%) were MRD negative in PB at the last staging during maintenance therapy. 11 pts discontinued maintenance therapy early due to AE (6 pts (10.2%)), progressive disease (PD), refusal of further treatment (2 pts (3.4%) each) or physician´s decision (1 pt (1.7%)). 15 pts (25.4%) completed 24 months and 33 pts (55.9%) stopped due to MRD negativity after a median time of 15.6 months on study. PFS and OS are shown in Figures 2 and 3. In 1L pts 4 PD (13.3%) and no deaths occurred while among RR pts 8 PD (25.8%) and 7 deaths were reported (3 due to infections, 2 due to progression of CLL, 1 due to comorbidity and 1 due to infection and unknown cause). Among pts who stopped treatment due to MRD negativity, 5 pts relapsed after a median duration of 16.4 months off treatment and 1 pt died after 8.7 months, respectively. During maintenance therapy, no grade 5 AE occurred. 151 (45.5%) of 332 CTC grades 1 - 4 AE were deemed as related to study drugs. Due to AE, I was dose modified in 26 pts (44.1%), G in 1 pt (1.7%). All grade 3-4 toxicities observed are shown in Table 2. Conclusion: The depth of response of the BIG regimen can be improved by maintenance therapy with I and G, leading to a rate of undetectable MRD in the PB in 71.2% of pts. Among 33 pts who discontinued treatment due to MRD negativity only 5 pts relapsed and 1 pt died so far. The data demonstrate that the BIG protocol using an MRD guided concept for treatment discontinuation yields very good results, in particular in 1L CLL pts. Disclosures Von Tresckow: Celgene: Other: Travel support; AbbVie: Consultancy, Honoraria, Other: Travel support; Roche: Consultancy, Honoraria, Other: Travel support, Research Funding; Janssen: Consultancy, Honoraria, Other: Travel support, Research Funding. Cramer:Acerta: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Other: travel support, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support, Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support, Research Funding; Roche: Honoraria, Other: travel support, Research Funding; mundipharma: Other: travel support. Langerbeins:Mundipharma: Other: travel support; Roche: Honoraria, Other: travel support; Janssen: Honoraria, Other: travel support, Research Funding; AbbVie: Honoraria, Other: travel support; Sunesis: Honoraria. Fink:Celgene: Research Funding; Roche: Other: travel grants; Janssen: Membership on an entity's Board of Directors or advisory committees. Al-Sawaf:Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: travel support; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support. Illmer:Roche: Other: travel support. Tausch:AbbVie: Consultancy, Honoraria, Other: travel support, Speakers Bureau; Roche: Consultancy, Honoraria, Speakers Bureau. Ritgen:AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support, Research Funding. Fischer:Roche: Other: travel grants; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees. Wendtner:Gilead Sciences, Inc.: Consultancy, Honoraria, Research Funding, Speakers Bureau; MorphoSys: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding, Speakers Bureau; Hoffman-La Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen-Cilag: Consultancy, Honoraria, Research Funding, Speakers Bureau. Kreuzer:Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Mundipharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Stilgenbauer:Gilead: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pharmacyclics: Other: Travel support; AstraZeneca: Consultancy, Honoraria, Research Funding, Speakers Bureau; Hoffmann La-Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; GSK: Consultancy, Honoraria, Research Funding, Speakers Bureau. Böttcher:AbbVie: Honoraria, Other: travel support; Becton Dickinson: Honoraria; Celgene: Other: tavel support; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support. Eichhorst:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; ArQule: Membership on an entity's Board of Directors or advisory committees; BeiGene: Research Funding; Gilead Sciences, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Hallek:AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Boehringer Ingelheim: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. OffLabel Disclosure: Obinutuzumab (GA101) is not registered for Treatment of relapsed/rferactory CLL