Summary
Relapsed/refractory diffuse large B‐cell lymphoma (DLBCL) is associated with a poor prognosis. Outcomes are particularly poor following immunochemotherapy failure or relapse within 12 months ...of induction. We conducted a Phase I/II trial of lenalidomide plus RICE (rituximab, ifosfamide, carboplatin, and etoposide) (RICER) as a salvage regimen for first‐relapse or primary refractory DLBCL. Dose‐escalated lenalidomide was combined with RICE every 14 d. After three cycles of RICER, patients with chemosensitive disease underwent stem cell collection and consolidation with BEAM BCNU (carmustine), etoposide, cytarabine, melphalan followed by autologous stem cell transplantation (autoSCT). Patients who recovered from autoSCT toxicities within 90 d initiated maintenance treatment with lenalidomide 25 mg daily for 21 d every 28 d for 12 months. No dose‐limiting or unexpected toxicities occurred with lenalidomide 25 mg plus RICE. Grade 3/4 haematological toxicities resolved appropriately, and planned dose density and dose intensity of RICER were preserved. No lenalidomide or RICE dose reductions were required in any of the three cycles. After two cycles of RICER, nine of 15 patients (60%) achieved a complete response, and two achieved a partial response (13%). Combining lenalidomide with RICE is feasible, and results in promising response rates (particularly complete response rates) in high‐risk DLBCL patients.
Introduction: Lenalidomide (Len) is an oral immunomodulatory agent with activity in CLL in both the front-line and relapsed settings. Recently Len has demonstrated significant improvements in PFS ...when studied as maintenance therapy following chemoimmunotherapy in the front-line and relapse settings (Fink, ASH 2016, Foà, ASH 2016) as well as in combination with R-fludarabine in the front-line setting (Rupert ASCO 2017, CALGB 10404). Here we present long-term follow-up of reduced-dose FCR (FCR-lite) in combination with Len followed by Len maintenance as a front-line CLL therapy.
Methods: We conducted a phase 2 study (NCT 01723839) examining the combination of FCR-lite and Len (“FCR²”) followed by Len maintenance for treatment naïve, CLL pts requiring therapy. Eligible pts (age ≥18 yr, ECOG ≤ 2, CrCl ≥30 ml/min) were treated with 4-6 cycles of FCR² (D1-3 fludarabine 20 mg/m², D1-3 cyclophosphamide 150 mg/m², D1&15 rituximab 500 mg/m² every 28 days). Pts with del17p, del11q and/or unmutated IGHV were not excluded. Len was administered on D 8-28 of each cycle (starting dose of 5 mg increasing to 10-15 mg in cycle ≥ 2 based on toxicity). Pts who were MRD (-) in PB and BM (4 color flow cytometry) initiated Len maintenance after cycle 4, otherwise pts proceeded to 6 cycles FCR² followed by Len maintenance. Len maintenance started two months after FCR² completion in responding pts (≥ PR) for a total of 12 months (5-15 mg daily, dose based on toxicity). The primary study endpoint was the proportion of complete remissions (CR) after cycle 4 of FCR² (≥ 40% CR+CRi considered a positive result, α 0.05, β 90%). Secondary endpoints included MRD status, ORR, PFS, OS and toxicity profile. We report the final analysis of primary and secondary study endpoints.
Results: 25 pts met inclusion criteria for enrollment of which 22 pts enrolled and 19 were evaluable (consent was withdrawn on 3 pts after ≤ 4 FCR cycles due to pt preference n=1, MD preference n=2, one additional pt withdrew consent after cycle 5 to proceed with SCT). Median baseline characteristics were as follows: age 62.5 yr (42-75 yr), ECOG PS 1 (0-2), WBC 115.4 x 109/L (8.7-301.7), Hb 12.2 g/dL (7.8-15.3), Plt 131 x 109/L (60-178), β2mg 2.8 μg/mL (1.74-6.69), LDH u/L 471 (132-1022), 30% pts had Rai stage III-IV, 53% unmutated IGHV, 5% del17p, 30% del11q. After 4 cycles of FCR (n=19) response rates were: ORR 94%, CR/CRi 52%, PR 42%, SD 5% (MRD (-) in 29% BM, 56% PB, 3 pts (16%) MRD (-) in PB and BM). After 6 cycles of FCR² (n=16), response rates were: ORR 95%, 76% CR/CRi, 19% PR, 5% PD (MRD (-) in 50% BM, 72% PB samples). During induction, 12 pts required a treatment interruption or dose reduction of Len (median Len dose = 10 mg) and the most common grade ≥3 toxicities were as follows (% events): neutropenia (51%), leukopenia (20%), hyperglycemia (5%), neutropenic fever (5%). Ten of 19 pts went on to receive Len maintenance (5 eligible pts withdrew consent, 3 pts were ineligible due to persistent cytopenias, 1 pt with PD). During maintenance, 8 pts required a treatment interruption or dose reduction of Len (median Len dose = 5mg, median number of monthly cycles = 12) and neutropenia was the only grade ≥ 3 toxicity (50%). With a median follow up of 39 months, median PFS was 43.8 months (figure 1). Median OS (figure 2) was not reached (one death recorded at the time of this analysis in allogeneic SCT patient in CR). One secondary malignancy has been recorded. Grade ≥ 3 TLS and tumor flare were not observed.
Discussion: Len can safely be combined with FCR-lite in the front-line setting and subsequently administered as maintenance therapy for 1 year in a pt population that included high-risk CLL and advanced age. As compared to prior Len maintenance series, this series is unique in that it provides long-term follow-up period (nearly 40 months) assessing both efficacy and toxicity and addresses appropriate Len dose in combination and maintenance. Immunomodulatory agents, as a drug class, are active in CLL and should be further investigated in the management of patients with CLL.
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Mato:Pharmacyclics: Research Funding; DTRM: Research Funding; Kite: Consultancy; Janssen: Consultancy; Portola: Research Funding; Gilead Sciences, Inc.: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy; AbbVie: Consultancy, Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Regeneron: Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Acerta: Research Funding. Goy:Genentech: Research Funding; Pharmacyclics / J&J: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Acerta: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Feldman:Bristol-Myers Squibb: Consultancy; Janssen: Speakers Bureau; Pharmacyclics: Speakers Bureau; Celgene: Speakers Bureau; Kite Pharma: Speakers Bureau; Seattle Genetics: Honoraria, Research Funding, Speakers Bureau; AbbVie: Speakers Bureau. Leslie:KITE pharma: Speakers Bureau; seattle genetics: Speakers Bureau; celgene: Speakers Bureau. Valentinetti:TG Therapeutics: Employment. Schuster:Gilead: Consultancy, Research Funding; Nordic Nanovector: Consultancy; Genentech: Consultancy, Research Funding; Janssen: Consultancy, Honoraria; Merck: Research Funding; Seattle Genetics: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy, Research Funding. Svoboda:Kite: Consultancy; Merck: Research Funding; Celgene: Research Funding; Pharmacyclics: Research Funding; Seattle Genetics: Consultancy, Research Funding; BMS: Consultancy, Research Funding. Foon:Celgene: Employment. Skarbnik:Genentech: Speakers Bureau; Seattle Genetics: Speakers Bureau; Abbvie: Other: Ad board, Speakers Bureau; Gilead: Speakers Bureau; Novartis: Speakers Bureau.
Introduction: The outcome of MCL patients (pts) has improved over the last three decades, although this is debated outside clinical trials (Chandran, Leuk Lymphoma Aug 2012; Smith, Br J Cancer. April ...2015). The Mantle Cell International Prognostic Index (MIPI) (Hoster, Blood Jan 2008) is based on 4 variables which predict survival: age (host factor), PS (tumor/host), LDH (tumor burden) and WBC (leukemic phase). The additional value of including co-morbidities into risk stratification has not been fully explored.
Methods: Using the COTA database we retrospectively analyzed MCL cases treated at John Theurer Cancer Center and the affiliated practices of Regional Cancer Care Associates from 2004 to 2016. Clinical and treatment characteristics, including calculation of the CCI index (Charlson J Chronic Diseases 1987) were captured via the COTA platform by extracting data from the electronic health records.
Results: 490 pts with MCL were evaluated and full longitudinal data from diagnosis is currently reported on 195 subjects. Pts characteristics included: male (66.15%), med age (65, range 34-94), stage IV (87%), LDH (elevated 26%; median 197, range 112-7950), MIPI (low 38%, interm 32%, high 30%), Ki-67 (≥30%: 51%, 86 NA), blastoid variant (16%, 35 NA), SOX-11 positive (87%, 143 NA), 17p abnormalities (p53 del or overexpression/mutation (24%, 88 NA) and b-2 microglobulin (b-2m) > 3 mg/L (52%). Frontline therapy consisted of R-Hyper-CVAD (with or without bortezomib on study) (36%), R-HyperCVAD or R-CHOP followed by high-dose therapy followed by autologous stem cell transplantation (ASCT) (9%), BR alone (8%), BR+ maintenance (8%), R-CHOP alone (4%), Rituximab (3%), R-BAC (3%), BR+ Ibrutinib vs placebo (2%), radiation (2%), R-Lenalidomide (1%), R-CHOP + maintenance (1%), other treatments (10%) while 10% of patients were treated expectantly Seventeen pts underwent ASCT consolidation (15 auto vs 2 allo (del17p/blastoid at presentation). Overall and progression free survival was computed using Kaplan Meier curves and significance tested using log-rank tests. The 5y OS for this entire cohort was 81. Overall, dose-intensive strategies (with or without ASCT) approach was associated with a 23 mo difference in PFS (median 74 mo, range 0-111 mo (intensive) vs median 51 mo, range 2-57 mo for the non-intensive group (p=0.37). The median OS was not reached for either group, with a 5y OS of 88% in intensive vs. 71% non-intensive regimens (p=0.14).
Using MIPI as stratification, low/intermediate risk pts had similar outcome in intensive and non-intensive therapy groups (5y OS 88% vs 71%; p=0.13). Pts with high MIPI had a 5 year OS of 80% in the intensive therapy group vs 46% for non-intensive group (p=0.376). The CCI scores for the whole cohort were 0 in 16 pts (8%), 1-3 in 81 pts (41%), and ≥ 4 in 98 pts (50%). Baseline CCI score (pre-treatment) was highly predictive of outcome with a 5y OS of 90% in CCI 0-3 vs 62% in CCI 3+ (p=0.001) (Figure 1). CCI did not predict complete response rate (CR) to induction therapy (CCI 0-3 94% vs CCI 3+ 80%). The median MIPI scores were 5.7 for CCI 0-3 and 6.3 for CCI 3+. Age is a component of both indexes but more heavily weighted in the CCI. Adding CCI to MIPI defined a subset of pts among the high MIPI group who did better than expected with a 5y OS of 88% in combined high MIPI / CCI 0-3 vs 31% for high MIPI / CCI 4+/ (p=0.03). b-2m (cut-off 3mg/L) correlated with 5y OS 93% vs 80%; (p=0.04) as previously reported but did not add to MIPI or CCI risk stratification. Ki-67 (30% cut-off) was marginally associated with OS: 5-y 89% vs 77% (p=0.06).
Conclusions: Our cohort is consistent with the improvement of MCL outcome comparing to historical controls and illustrates the importance of comorbidities captured at baseline. A combined CCI-MIPI approach might help identify pts who can still benefit from current therapy approaches in spite of age. Among the high MIPI score group, CCI further refines cohorts with significantly different outcomes.
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Goy:Acerta: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech: Other: Research funding for clinical trials through institution; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; COTA: Membership on an entity's Board of Directors or advisory committees; Janssen/Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Research funding for clinical trials through institution, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Research funding for clinical trials through institution. Wu:COTA: Employment. Hansen:COTA: Employment. Arunajadai:COTA: Employment. Protomastro:COTA: Employment. Valentinetti:COTA: Employment. Murphy:COTA: Employment. Smith:COTA: Employment. Pe Benito:COTA: Employment. Hasan:COTA: Employment. Suryadevara:COTA: Employment. Feldman:Seattle Genetics: Consultancy, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Pharmacyclics: Speakers Bureau; Celgene: Speakers Bureau. Skarbnik:Pharmacyclics: Consultancy; Genentech: Speakers Bureau; Seattle Genetics: Speakers Bureau; Gilead Sciences: Speakers Bureau; Abbvie: Consultancy. Leslie:Celgene: Speakers Bureau; Seattle Genetics: Speakers Bureau. Pecora:COTA: Employment, Equity Ownership. Goldberg:Bristol Myers Squibb, Novartis: Speakers Bureau; Neostem: Equity Ownership; Novartis: Consultancy; COTA Inc: Employment; Pfizer: Honoraria.
Background: Rituximab has increased the CR rate, improved both PFS and OS and changed the pattern of relapse of DLBCL pts treated with R-CHOP (leading to a > 50% cure). In contrast to the pre ...rituximab era, the majority of failures occur early (80% of failures occur in the 1st 18 months). The observation made that few relapses (7-8%) occur after 24 months of pts enrolled in clinical trials needs validation in the community setting. We report here a large cohort of pts treated at our institution over a period of 7 years with rituximab-containing chemotherapy regimens.
Methods:We performed a retrospective cohort analysis to describe the survival experiences of adult patients with de novo DLBCL treated at our institution between 2007 and 2013. Patients were identified using Hematopathology and John Theurer Cancer Center outcomes databases. Patients who didn’t receive rituximab as part of their initial combination chemotherapy were excluded, as well as transformed DLBCL, primary CNS DLBCL, HIV-related DLBCL pts, those lacking follow up data.
Results: A total of 245 patients with DLBCL treated at our institution were identified. Baseline characteristics were as follows: median age was 63 (20-92), 53% males, 75% stage III-IV and 24% stage I-II; IPI score was high in 25% of pts, high-int in 22%, low-int in 45% and low in 7%. Most patients received R-CHOP (66%), while 34% were treated with dose intense regimens based on high risk features such as high IPI, Ki-67 over 80% (R-HyperCVAD, DA-R-EPOCH, R-Magrath), only two patients had frontline planned stem cell transplant. 91% of the patients achieved a CR, 7% were primary refractory (progressed during therapy), 2% PR/SD ). With a median follow up time of 32.5 months, the median OS and PFS have not been reached (75% of patients are alive at 55.9 months). In contrast, the median OS of relapsed patients was only 14.4 months No gender-specific differences in survival were observed. No differences in PFS and OS were observed based on frontline chemotherapy regimen. Achieving CR significantly determines survival (p.<05, LR test). Relapses occurred within first 24 months in 54 out of total of 60 patients who relapsed after frontline therapy.
Conclusion: Our series confirm outside clinical trial setting that in contrast to the pre-rituximab era, late relapses are rarely observed in patients treated with rituximab–containing induction therapy. The majority of relapses occur within the first two years of the initial therapy. Our findings validate the data from the Mayo clinic experience (Maurer et al, JCO 2014). This observation not only provides reassurance to patients but also support the current imaging guidelines with no longer a need for routine imaging surveillance for relapse in DLBCL beyond 2 years after frontline therapy.
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No relevant conflicts of interest to declare.
Introduction: Fludarabine, cyclophosphamide, rituximab (FCR) remains the standard of care for the treatment of newly diagnosed, fit CLL pts requiring therapy. However, the FCR side effects profile is ...non-trivial and CLL pts with poor risk features have inferior outcomes. Strategies aimed at minimizing toxicity without compromising efficacy have been reported including modifications of the optimal dosing and duration of FCR using a dose-reduced approach (Foon et al, “FCR lite”) or reduction in number of FCR cycles based on MRD status (Strati et al). In the era of biological agents, both preclinical and clinical data have shown the efficacy of lenalidomide (Len) in CLL likely through its role as an immunomodulator and interference with interactions between CLL and its microenvironment. In CLL, Len presents a clinical opportunity both in combination with chemotherapy and as maintenance strategy. This was the rationale for our trial using Len in combination with FCR and as maintenance to improve outcomes and shorten therapy.
Methods: We conducted a phase 2 cohort study examining the combination of dose-reduced FCR and Len (“FCR2”) followed by Len maintenance for treatment naïve, CLL pts requiring therapy (NCIWG criteria). Eligible pts (age ≥18 yr, ECOG 0-2, CrCl ≥30 ml/min, absence of AIHA) were treated with 4-6 cycles of FCR2 (D1-3 fludarabine 20 mg/m2, D1-3 cyclophosphamide 150 mg/m2, D1&15 rituximab 500 mg/m2 every 28 days). Len was administered on D 8-28 of each cycle (starting dose of 5 mg increasing to 10 mg and 15 mg in cycle ≥ 2 based on toxicity algorithm). Pts who were MRD (-) in PB and BM (multicolor flow cytometry) initiated Len maintenance after cycle 4 FCR2 (otherwise proceeded to 6 cycles). Supportive care included asa 81 mg, pegfilgrastim, and antimicrobial prophylaxis (ciprofloxacin, bactrim, fluconazole, acyclovir). Daily Len maintenance started two months after FCR2 completion in responding pts for a total of 12 months (5-15 mg based on toxicity algorithm). The primary study endpoint was the proportion of CR pts after cycle 4 of FCR2 with ≥ 8/19 (≥ 40%) CR+CRi considered a positive result and worthy of further study (α 0.05, β 90%). Secondary endpoints included MRD status, ORR, OS, PFS and toxicity (CTCAE V. 4.0). We report the primary endpoint and preliminary data on non-survival secondary endpoints.
Results: 25 pts met inclusion criteria for enrollment of which 22 pts enrolled and 19 were evaluable (consent was withdrawn on 3 pts after ≤ 4 FCR2 cycles due to pt preference n=1, physician preference n=2, one additional pt withdrew consent after cycle 5 to proceed with Allo SCT.) Baseline characteristics expressed as median (range) were as follows: age 62.5 yr (42-75 yr), ECOG PS 1 (0-2), WBC 115.4 x 109/L (8.7-301.7), Hb 12.2 g/dL (7.8-15.3), Plt 131 x 109/L (60-178), IgG 602 mg/dL (294-1018), β2mg 2.8 μg/mL (1.74-6.69), LDH u/L 471 (132-1022), BM % lymphs 75 (25-100%), baseline SPD 23.4 (2.9-63.5). In addition 30% pts had Rai stage III-IV, 53% unmutated-CLL, 5% del17p and 30% del11q. After 4 cycles of FCR2 (n=19) response rates were as follows CR 47%, CRi 5%, PR 42%, SD 5% (pts were MRD neg in 29% BM and 56% PB samples, 3 pts (16%) were MRD neg in both PB and BM). After 6 cycles of FCR2 (n=16), response rates improved and were as follows: 63% CR, 13% CRi, 19% PR, 5% PD (pts were MRD neg in 50% BM and 72% PB samples). Table 1 shows MRD status following 4 and 6 cycles of FCR2. During induction, 12 pts required a treatment interruption or dose reduction of Len per protocol (median dose of len was 10 mg). The most common grade 3-4 toxicities were as follows (% events): neutropenia (51%), leukopenia (20%), hyperglycemia (5%), NTP fever (5%). Grade 3-4 TLS and tumor flare were not noted. The med follow up for the entire cohort is 13.1 months (7.3-22.5 months). One progression has occurred in a pt who withdrew from study after 2 cycle of FCR2. One death has occurred in a pt with del17p who died on D+255 following allogeneic SCT in CR from the complications of cGVHD. 10 pts have gone on to initiate Len maintenance.
Conclusions: FCR-lite in combination with Len is feasible and demonstrates encouraging clinical activity in a high-risk, CLL pt population with an acceptable toxicity profile. A significant proportion of pts are MRD neg in PB and/or BM following FCR2. Addition of Len to FCR may minimize chemotherapy exposure without compromising outcome. Table 1:MRD StatusFollowing Cycle 4 FCR2Following Cycle 6 FCR2Bone Marrow29%50%Peripheral Blood56%72%
Mato:Celgene : Honoraria, Research Funding, Speakers Bureau.
Abstract 3710
Relapsed/refractory DLBCL has poor prognosis in the rituximab era. Pts who failed Rituximab-containing initial chemo regimen within 12 mo do particularly poorly. (ORR 46–51% vs. 83–88%, ...EFS 20% vs. 45% at three years). Novel salvage therapies to overcome chemo resistance and maintain remission in post transplant setting are needed.
The immunomodulatory agent lenalidomide has demonstrated direct tumoricidal and antiproliferative effects in lymphoma and clinical activity and safety in multiple phase II studies in aggressive NHL.
We are conducting a phase I/II trial combining lenalidomide with RICE (rituximab, ifosfamide, carboplatin and etoposide) (RICER) as a salvage regimen in first relapse or primary refractory DLBCL. Four dose levels of lenalidomide are being evaluated in Phase I part of the study: 10mg, 15mg, 20mg, and 25mg given for 7 days (days 1–7) together with RICE. After three cycles of RICER patients with chemo sensitive disease proceed to stem cell collection (off 3rdRICE) and consolidation with BEAM followed by autologous SCT (ASCT). Patients who recover from ASCT toxicities within 90 days are started on maintenance with lenalidomide 25mg daily for 21 days every 28 days for 12 months.
13 patients have been enrolled. DLT was not seen at 25 mg (last dose level tested) of lenalidomide during the salvage part of RICER. No unexpected toxicities were observed by adding lenalidomide to RICE. Grade 3 and 4 hematologic toxicities were comparable to RICE alone and resolved appropriately and planned dose density and dose intensity of RICER were preserved. One episode of febrile neutropenia occurred during RICER administration. No new DVT’s occurred during lenalidomide administration either in salvage or in post ASCT maintenance part of the trial. Stem cell collection was successful in all but one patient. So far seven patients have completed ASCT and five patients were able to start on maintenance lenalidomide post transplantation. No unusual toxicities were observed in the peritransplantation period and there was no delay in engraftment: median days to ANC of >500 is 11, and to plts over 20K/mL is 11. In the maintenance post ASCT there was no infection but routine dose reductions were required because of myelotoxicity.
1.Adding lenalidomide to RICE (RICER) is feasible salvage regimen with no increased toxicity.2.PET-CR rate is promising in this very refractory DLBCL population.3.While it is premature for any definitive conclusions regarding feasibility of maintenance lenalidomide in post transplant setting, trial is ongoing with expansion in additional institutions.Table 1Patient characteristicsNumber of patients13Male/female10/3Median age64 (47–75)Disease characteristicNumber of patientsStage at relapse III-IV8 out of 13Relapse IPI6Low, low intermediate7Intermediate high, highPrimary refractory6Relapse <12 months of initial therapy5Relapse >12 mo of initial therapy2Rituximab used with initial therapy13Initial therapy9R-CHOP3R-HCVAD/R-MA1R-CODOX-M/IVACOverall response (OR)9Complete response (CR)8Partial response (PR)1Stable disease (SD)3Progression of disease (PD)1Auto SCT characteristicsStem cell harvest5.24 mln/kg (range 3.37–12.8mln/kg)Median time to platelets recovery to 20,000/mL without transfusional support12 days (range 7 to 14)Median time to ANC >500/mL11 days (range 9 to 11)
Feldman:allos: Speakers Bureau; merck: Speakers Bureau; celgene: Speakers Bureau; seattle genetics: Speakers Bureau. Off Label Use: Lenalidomide in combination with chemotherapy as salvage regimen for DLBCL. Mato:Celgene: Speakers Bureau; seattle genetics: Speakers Bureau; genentech: Speakers Bureau; millennium: Speakers Bureau. Goldberg:Eisai: Speakers Bureau. Vesole:Celgene Corp.: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Millennium: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau. Siegel:Celgene: Advisory Board Other, Honoraria, Speakers Bureau; Millennium Pharma: Advisory Board, Advisory Board Other, Honoraria, Speakers Bureau; Onyx: Advisory Board, Advisory Board Other, Honoraria, Speakers Bureau; Merck: Advisory Board, Advisory Board Other, Honoraria, Speakers Bureau. Goy:Milennium: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity’s Board of Directors or advisory committees; Seattle Genetics: Membership on an entity’s Board of Directors or advisory committees; Pharmacyclics: Membership on an entity’s Board of Directors or advisory committees; J & J: Membership on an entity’s Board of Directors or advisory committees; Pfizer: Membership on an entity’s Board of Directors or advisory committees.
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