Despite generally high cure rates in patients with metastatic germ cell cancer, patients with progressive disease on first-line cisplatin-based chemotherapy or with relapsed disease following high-dose salvage therapy exhibit a very poor prognosis. Irinotecan has shown antitumour activity in human testicular tumour xenografts in nude mice. We have performed a phase II study examining the single agent activity of irinotecan in patients with metastatic relapsed or cisplatin-refractory germ cell cancer. Refractory disease was defined as progression or relapse within 4 weeks after cisplatin-based chemotherapy or relapse after salvage high-dose chemotherapy with autologous stem cell support. Irinotecan was administered at a dose of 300 (−350) mg m −2 every 3 weeks. Response was evaluated every 4 weeks. Fifteen patients have been enrolled. Median age was 35 (19–53) years. Primary tumour localisation was gonadal/mediastinal in 12/3 patients. Patients had been pretreated with a median of six (4–12) cisplatin-containing cycles and 13 out of 15 patients had previously failed high-dose chemotherapy with blood stem cell support. Median number of irinotecan applications was two (1–3). Fourteen patients are assessable for response and all for toxicity. In one patient, no adequate response evaluation was performed. Toxicity was generally acceptable and consisted mainly of haematological side effects with common toxicity criteria 3° anaemia (two patients), common toxicity criteria 3° leukocytopenia (one patient) and common toxicity criteria 3° thrombocytopenia (three patients). Common toxicity criteria 3/4° non-haematological toxicity occurred in five patients (33%): 1×diarrhoea, 2×alopecia, 1×fever and in one patient worsening of pre-existing peripheral polyneuropathy from 1° to 4°. No response was observed to irinotecan therapy. Currently, 13 patients have died of the disease and two patients are alive with the disease. The patients included in our study exhibit similar prognostic characteristics as patients treated in previous trials evaluating new drugs in this setting. Irinotecan at a dose of 300–350 mg m −2 every 3 weeks appears to have no antitumour activity in patients with cisplatin-refractory germ cell cancer and, thus, further investigation in this disease is not justified. British Journal of Cancer (2002) 87 , 729–732. doi: 10.1038/sj.bjc.6600524 www.bjcancer.com © 2002 Cancer Research UK
Introduction: In chronic lymphocytic leukemia (CLL), improved anti-CD20 antibodies such as obinutuzumab (GA101) and targeted drugs, such as ibrutinib, show very good efficacy and tolerability. With the CLL2-BIG trial, the German CLL Study Group designed a regimen composed of obinutuzumab and ibrutinib for induction and maintenance therapy. Patients with high tumor burden receive bendamustine as debulking resulting in the proposed "sequential triple-T" concept [Hallek M., Blood 2013] of a tailored and targeted treatment aiming at total eradication of minimal residual disease (MRD). Here we present the results of the primary endpoint analysis of the trial. Methods : This prospective, open-label, multicenter phase-II trial investigates 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 and relapse/refractory treatment. Six cycles of induction treatment with obinutuzumab and ibrutinib were administered followed by maintenance therapy with continuous ibrutinib and obinutuzumab 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 received two cycles of bendamustine before start of induction. The primary endpoint is overall response rate (ORR) three month after the start of last induction cycle administered; secondary endpoints include ORR after debulking, MRD evaluations and safety parameters (graded per the NCI CTCAE v.4 criteria). Results: 66 pts were enrolled between January and August 2015. Five pts completed less than two cycles of induction and were therefore excluded from the full analysis set as defined by protocol. The current analysis includes 58 pts; an update including all 61 pts will be available for presentation at the meeting. The median age was 65.5 (range 36-83) years and the median time since initial diagnosis was 56.2 (2.1 - 222.8) months. 27 pts were treatment-naïve and 31 relapsed/refractory with a median of one prior treatment line (1-5). Baseline characteristics are summarized in table 1. 41 pts (71%) received bendamustine debulking, of these 27 pts (66%) responded; five pts (12%) achieved clinical complete remission (CR), 3 pts (7%) clinical CR with incomplete recovery of the bone marrow (CRi) and 19 pts (46%) partial remission (PR). 57 pts completed six cycles of induction treatment. One patient died after the fifth course due to grade 5 duodenitis related to study therapy. The combination showed promising efficacy with an ORR of 100% by investigator assessment at the end of induction. Statistically, the primary endpoint was met and the null hypothesis could be rejected. Response rates are presented in table 2. 27 pts (47%) achieved MRD negativity (< 10-4 by flow cytometry) in peripheral blood (pB) at the end of induction. An intermediate MRD-status (≥ 10-4 and < 10-2) was found in 15 pts (26%) whereas 13 pts (22%) were MRD positive (≥ 10-2). In three pts (5%) no MRD sample was available. So far, 38 pts (65%) received at least one dose of maintenance treatment; one patient already stopped treatment due to MRD negativity as defined per protocol. CTC Grade 3-4 adverse events occurred in 19 pts (33%) during induction therapy. The most common toxicities observed are shown in table 3. *The table includes all grade 3-4 AEs regardless of frequency and AEs of any grade observed in at least six patients. Conclusion: With an ORR of 100% and an MRD negativity rate of 47% in the pB the BIG-regimen showed a very good efficacy in a heterogeneous study population. No major toxicity occurred so far. Table 1. Demographics and baseline characteristics Table 1. Demographics and baseline characteristics Table 2. Response rates Table 2. Response rates Table 3 Safety Table 3. Safety Disclosures von Tresckow: Janssen-Cilag: Honoraria, Other: Travel grants, Research Funding; Celgene: Other: Travel grants; Hoffmann-LaRoche: Other: Travel grants, Research Funding. Cramer:Astellas: Other: Travel grants; Janssen-Cilag: Honoraria, Other: Travel grants, Research Funding; GlaxoSmithKline/Novartis: Research Funding; Gilead: Other: Travel grants, Research Funding; Hoffmann-LaRoche: Honoraria, Other: Travel grants, Research Funding; Mundipharma: Other: Travel grants. Bahlo:F. Hoffman-La Roche: Honoraria, Other: Travel grant. Engelke:Hoffmann-LaRoche: Other: Travel grants. Langerbeins:Hoffmann-LaRoche: Honoraria, Other: Travel grants, Research Funding; Janssen-Cilag: Honoraria, Other: Travel grants, Research Funding; Mundipharma: Honoraria, Other: Travel grants, Research Funding. Fink:Mundipharma: Other: Travel grants; Celgene: Other: Travel grants, Research Funding; AbbVie: Other: Travel grants; Hoffmann-LaRoche: Other: Travel grants. Illmer:Hoffmann-LaRoche: Honoraria, Other: travel grants. Ritgen:Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding. Fischer:Hoffmann-LaRoche: Other: Travel grants. Wendtner:Mundipharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Research Funding; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Research Funding; GlaxoSmithKline: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Research Funding; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Research Funding; Hoffmann-LaRoche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Research Funding. Stilgenbauer:Janssen: Consultancy, Honoraria, Other: Travel grants , Research Funding; Hoffmann-La Roche: Consultancy, Honoraria, Other: Travel grants , Research Funding; Pharmacyclics: Consultancy, Honoraria, Other: Travel grants , Research Funding; Amgen: Consultancy, Honoraria, Other: Travel grants, Research Funding; GSK: Consultancy, Honoraria, Other: Travel grants , Research Funding; Mundipharma: Consultancy, Honoraria, Other: Travel grants , Research Funding; Genentech: Consultancy, Honoraria, Other: Travel grants , Research Funding; Boehringer Ingelheim: Consultancy, Honoraria, Other: Travel grants , Research Funding; Celgene: Consultancy, Honoraria, Other: Travel grants , Research Funding; Novartis: Consultancy, Honoraria, Other: Travel grants , Research Funding; Sanofi: Consultancy, Honoraria, Other: Travel grants , Research Funding; Gilead: Consultancy, Honoraria, Other: Travel grants , Research Funding; AbbVie: Consultancy, Honoraria, Other: Travel grants, Research Funding; Genzyme: Consultancy, Honoraria, Other: Travel grants , Research Funding. Böttcher:AbbVie: Honoraria, Research Funding; Hoffmann-LaRoche: Honoraria, Other: Travel grants, Research Funding; Celgene: Research Funding. Eichhorst:Abbvie: Consultancy; Mundipharma: Consultancy, Research Funding, Speakers Bureau; Roche: Consultancy, Research Funding, Speakers Bureau. Hallek:Amgen: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Janssen-Cilag: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Mundipharma: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; F. Hoffmann-LaRoche: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau.
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
Introduction: In chronic lymphocytic leukemia (CLL) treatment with anti-CD20 antibodies including obinutuzumab (GA101) and targeted drugs, such as ibrutinib, show promising efficacy and tolerability compared to standard chemoimmunotherapy. With the CLL2-BIG trial, the German CLL Study Group (GCLLSG) designed a novel combination regimen composed of obinutuzumab and ibrutinib for induction and maintenance treatment. To reduce the risk of severe infusion related reactions (IRR) during the first infusion of obinutuzumab, patients with high tumor burden receive bendamustine as debulking resulting in the proposed "sequential triple-T" concept [Hallek M., ASH 2013] of a t ailored and t argeted treatment aiming at t otal eradication of minimal residual disease (MRD). Methods: The phase-II CLL2-BIG trial investigates the safety and efficacy of a novel regimen for physically fit and unfit CLL patients, irrespective of high-risk genetics. 62 patients had to be recruited according to a predefined allocation for the two strata of first-line and relapse treatment. Six cycles of induction treatment with obinutuzumab and ibrutinib are administered followed by maintenance therapy with ibrutinib and obinutuzumab every three months until achievement of MRD-negative complete remission or up to 24 months. Patients with initial high tumor burden (absolute lymphocyte count > 25.000/µl and/or lymph nodes > 5cm) receive two cycles of debulking with bendamustine before start of induction. Primary endpoint is overall response rate (ORR) at the end of induction; secondary endpoints include ORR after debulking and maintenance, MRD evaluations as well as safety and survival parameters. Results: As of July 2015, 62 patients were included. Of these, 29 were treatment-naïve and 33 relapsed/refractory. The median age was 65.5 (36-86) years, the median time from initial diagnosis 4.8 (0.2 - 18.6) years and the median cumulative illness rating scale (CIRS) score 2 (0-11). Among 55 pts with cytogenetic analyses, 10 patients had a del(17p) and 40 patients an unmutated IGHV status. 44 patients (71%; 26 first-line and 18 relapsed/refractory) received bendamustine debulking. Four patients stopped treatment after the first course of debulking, one due to physicians' decision, two patients withdrew their consent and one patient died. During debulking 11 serious adverse events (SAE) occurred in 7 patients: four infections (including three pneumonias and one fatal sepsis) in four patients, two surgical interventions for a known cataract in one patient and one tumor lysis syndrome (TLS), one pyrexia, one systemic inflammatory response syndrome, one worsening of renal insufficiency and one diarrhea. Thus far, obinutuzumab was administered to 41 patients of whom 22 received prior debulking. In 19 patients debulking was omitted due to contraindications or low tumor burden. 14 IRRs (CTC AE v4.0 grade I-III) were reported in connection with infusions of obinutuzumab in 13 patients. Only 4 IRRs occurred after two cycles of debulking (18%). In contrast, 10 IRRs were observed without prior debulking (48%). 2 IRRs were reported as SAEs, one after prior debulking and one without. No grade IV IRRs occured so far. IRRs were reported during the first infusion in 9 patients, during the second infusion in three patients and during the first and second infusion in one patient. There were no IRRs after the first two infusions of obinutuzumab. In addition, after prior debulking two SAEs were reported during the first induction cycle: IRR and thrombocytopenia. Without prior debulking two SAEs (IRR and pneumonia) occurred during the first and two SAEs (upper abdominal pain and lymph node abscess) during subsequent induction cycles. Occurrence of IRRs and baseline characteristics of all patients as well as first efficacy data will be available for presentation at the meeting. Conclusion: In the CLL2-BIG trial, a combination regimen consisting of obinutuzumab and ibrutinib after prior debulking with bendamustine for patients with high CLL tumor load is investigated. So far, the data suggest that debulking prior to obinutuzumab might reduce the occurrence of severe IRRs compared to historical data [Goede V., NEJM 2014] and to patients who did not receive debulking. The rate of infections seen with bendamustine in this trial seems comparable to previous reports for bendamustine monotherapy in CLL [Bergmann M., Haematologica 2005 and Knauf W., JCO 2010]. Disclosures von Tresckow: Hoffmann-LaRoche: Other: travel grants, Research Funding; Janssen: Honoraria, Research Funding; Celgene: Other: travel grants. Off Label Use: Combination of bendamustine, obinutuzumab and ibrutinib for treatment of CLL. Cramer:Janssen: Other: Travel grant, Research Funding, Speakers Bureau; Gilead: Other: Travel grant, Research Funding; Glaxo Smith Klein/Novartis: Research Funding; Astellas: Other: Travel grant; Mundipharma: Other: Travel grant; Hoffman LaRoche: Other: Travel grant, Research Funding, Speakers Bureau. Engelke:Hoffmann-LaRoche: Other: travel grants. Langerbeins:Janssen: Honoraria, Other: travel grants, Research Funding; Hoffmann-LaRoche: Honoraria, Other: travel grants, Research Funding; Mundipharma: Honoraria, Other: travel grants, Research Funding. Fink:Roche: Honoraria, Other: travel grant. Tausch:Gilead: Other: Travel support. Fischer:Roche: Other: Travel Grants. Wendtner:Celege: Consultancy, Other: Travel grants, Research Funding; Hoffmann-LaRoche: Consultancy, Other: travel grants, Research Funding; Genentech: Consultancy, Other: travel grants, Research Funding; Gilead: Consultancy, Other: travel grants, Research Funding; Glaxo-SmithKline: Consultancy, Other: travel grants, Research Funding; Janssen-Cilag: Consultancy, Other: travel grants, Research Funding; Mundipharma: Consultancy, Other: travel grants, Research Funding; Pharmacyclics: Consultancy, Other: travel grants, Research Funding; AbbVie: Consultancy, Other: travel grants, Research Funding. Stilgenbauer:Roche: Honoraria, Research Funding. Boettcher:Roche: Honoraria, Other: travel grants, Research Funding; AbbVie: Honoraria, Research Funding; Celgene: Research Funding. Eichhorst:Roche: Consultancy, Research Funding, Speakers Bureau; AbbVie: Consultancy; MundiPharma: Consultancy, Research Funding, Speakers Bureau. Hallek:Gilead: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Boehringher Ingelheim: Honoraria, Other: Speakers Bureau and/or Advisory Boards; Mundipharma: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Celgene: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Janssen: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Roche: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Pharmacyclics: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; AbbVie: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding.
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