ALBERT

Description: Abstract 3666 Introduction With the FDA and EMA approval of Bendamustine a new treatment option has recently become available to patients (pts) with indolent (low-grade) non-Hodgkin lymphoma (iNHL). Clinical registries provide insight into real-life treatment of pts. They can help to answer the question whether patients may benefit from new research findings. Methods The clinical registry on lymphoid neoplasms (TLN Registry), conducted by iOMEDICO in collaboration with the Arbeitskreis Klinische Studien (AKS) and the Kompetenznetz Maligne Lymphome (KML), prospectively collects data on the treatment of pts with lymphoid B-cell neoplasms as administered in hematology outpatient centres in Germany. Pts are followed for 5 years. A broad set of data regarding patient and tumor characteristics, comorbidities, all systemic treatments, response rates, progression-free survival and overall survival are recorded. Since May 2009, 106 sites have actively recruited a total of 2579 pts. Results From the overall sample, 645 pts received systemic 1st-line treatment for indolent Non-Hodgkin lymphoma (iNHL). 53% of pts are male, mean age at time of primary diagnosis was 65 years (yrs) and at start of therapy 66 yrs. Tumor stage was 7% Stage I, 15% Stage II, 25% Stage III and 54% Stage IV. 61% of pts (n=387) were diagnosed with at least one comorbidity, mainly hypertension (33%) or diabetes (12%); the average Charlson Comorbity Index of 0.6 indicates that pts have few comorbities. Rituximab is part of the 1st-line treatment in 94% (n=606) of pts with iNHL. Bendamustine is part of the 1st-line treatment in 71% (n=455) of pts with iNHL. It is mostly applied in combination with Rituximab (BR, 66%, n=428). Further 2% (n=10) receive Bendamustin as monotherapy. Rituximab/Cyclophosphamide/Doxorubicin/Vincristine/Prednisone (R-CHOP) as 1st-line treatment is applied in 16% (n=105) of pts with iNHL. Pts receiving BR or R-CHOP differ. Pts characteristics indicate that BR is applied preferably in elderly pts (mean 67.3 vs. 60.9 yrs). However, BR is the preferred treatment also in pts younger than 66 yrs (60% vs. 23%). The use of BR has increased from 62% in 2009 to 68% in 2011, whereas the rate of R-CHOP has decreased from 19% in 2009 to 15% in 2011. Of all pts with iNHL, 121 have received 2nd-line treatment. Rituximab is part of the 2nd-line treatment in 84% (n=102) of pts with iNHL. Bendamustine is part of the 2nd-line treatment in 68% (n=82) of pts with iNHL. It is mostly applied in combination with Rituximab (BR, 60%, n=72). Further 7% (n=9) receive Bendamustin as monotherapy. R-CHOP as 2nd-line treatment is applied in 7% (n=9) of pts with iNHL. Conclusion BR is the most frequently used systemic treatment for pts with iNHL in German hematology outpatient centres. The use of BR has continuously increased since 2009. In contrast, the use of R-CHOP has decreased. This indicates that in Germany R-CHOP can no longer be considered as “standard of care” for pts with iNHL. These data also show that results from clinical trials are quickly implemented into daily practice. The impact of BR on quality of life and survival remains to be of central interest in the future. Disclosures: Knauf: Mundipharma GmbH: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Description: CT-associated cognitive dysfunction, which frequently manifests as subtle changes in memory, concentration, and ability to remain focused or organized, can adversely affect cancer pts’ QOL. EPOLYM, a prospective, international, multicenter, open-label, phase IIIb trial has been conducted to investigate the efficacy, safety, and clinical outcomes, including effect on cognitive function, of epoetin alfa 40,000 IU sc QW in anemic (Hb

Description: Abstract 4606 Introduction: The treatment of patients with Chronic Lymphocytic Leukemia (CLL) has changed significantly over the last years. To select an appropriate treatment, multiple factors have to be considered. In particular, the stage of disease, patient’s age, comorbidities and personal preferences, respectively, influence decision making. The clinical tumor registry on lymphoid neoplasms (TLN Registry) conducted by the iOMEDICO AG in collaboration with the Arbeitskreis Klinische Studien (AKS) and the Kompetenznetz Maligne Lymphome (KML) was established to collect data on the daily practice treatment of 3000 non-selected patients with lymphoid neoplasms. Here, we present data regarding treatment and sequences of regimes in patients (pts) with CLL treated by office-based hematologists in Germany. Methods: While targeting 500 CLL pts, the registry prospectively collects data on pts characteristics, tumor history, treatment, response rates and sequences of regimes. In addition data on adverse drug reactions and concomitant diseases are documented. CLL pts older than 18 years receiving a first- or second line therapy which has started no longer than 4 weeks before patient enrolment can be recruited into the registry if informed written consent is present. All pts are followed for 5 years. Currently, 116 sites across Germany are participating. Results: The TLN Registry started in May 2009. Currently, 492 pts with CLL have been recruited. The mean age at the start of first line therapy is 69 years. The majority of pts (63%) are male. About 20% of the pts in first line therapy are treated within clinical trials. Median time between diagnosis and start of first line therapy is 22 months (range 0 – 285 months). Most of the pts receive Bendamustine/Rituximab (BR, 34%) or Fludarabin/Cyclophosphamide/Rituximab (FCR, 21%) in first line therapy. Overall, 97% of the first line therapies were successful (91% CR/PR, 6% SD). In particular, 99% of BR (98% CR/PR, 1% SD) and 100% of FCR (98% CR/PR, 2% SD) therapies were successful. Over time, a change in treatment selection becomes apparent. 50% of the pts started first line therapy before October 2009. They mainly received BR (19%), Bendamustine (16%), FCR (16%) or Chlorambucil (15%), respectively. Pts starting first line therapy after October 2009 mainly received BR (43%) or FCR (24%). Bendamustine-containing regimens are more often used as first line therapy in pts older than 75 years as compared to younger ones (62% vs. 42%). Fludarabine-containing regimens are more often used in pts younger than 75 years (37% vs. 6%). Similar to the first line therapy, BR is the most often used second line therapy (52%). About 41% of the pts have completed first line therapy and have not yet started second line therapy. The median treatment-free interval since the end of the first line therapy is 10 months. Data on second line therapy are available in 24% of the pts. The majority of these pts (73%) were recruited at the start of second line therapy. Most of them receive BR as second line therapy after first line therapy either with Chlorambucil (17%) or Bendamustine (13%). The median treatment-free interval between the end of first line therapy and the start of second line therapy is 16 months (range 1 – 49 months). Conclusion: The registry provides an overview on particularities and changes in routine treatment of pts with CLL treated by office-based hematologists in Germany. Implementation of new standards affecting treatment preferences are currently under evaluation. BR and FCR are widely accepted and very effective as first line therapies. Our data indicate that age is an important factor for selecting the appropriate treatment. Further analyses will investigate additional variables influencing the choice of treatment. With more data becoming available the sequences of regimes and their effectiveness can be analyzed. Disclosures: No relevant conflicts of interest to declare.

Description: Introduction Combination immunochemotherapy with cyclophosphamide, doxorubicine, vincristine, prednisone and the anti-CD20 monoclonal antibody rituximab (R-CHOP) is the standard of care for patients (pts) with previously untreated high-grade (aggressive) non-Hodgkin’s lymphoma (aNHL). Dose intensification of CHOP has shown ambiguous results (Pfreundschuh, 2004; Ohmachi, 2011), but the dose-dense two-weekly schedule (R-CHOP-14) was not found to be superior to the three-weekly schedule (R-CHOP-21) (Cunningham, 2013). Since clinical trials are restricted to highly selected pts, we investigated effectiveness of R-CHOP-14 and R-CHOP-21 in unselected pts with aNHL treated in routine practice by German office-based haematologists. Methods The open, longitudinal, multicentre, clinical registry on lymphoid neoplasms (TLN Registry, ClinicalTrial.gov registry NCT00889798) prospectively collects data on the treatment of pts with lymphoid B-cell neoplasms as administered by a network of over 260 German office-based haematologists. The choice of therapy is upon the discretion of the treating physician. All pts give their informed consent before onset of therapy. Pts are followed for 5 years. A broad set of data regarding patient and tumour characteristics, co-morbidities, all systemic treatments and response rates, date(s) of progression(s) and date of death are recorded. Automated plausibility and completeness checks with subsequently generated queries by the electronic data capture system ensure data reliability. In addition, data managers regularly check for plausibility and issue queries. Between May 2009 and August 2013 (date of present analysis), a total of 3,383 pts have been recruited. Results Of 477 pts with aNHL (95% DLBCL), recruited at the start of 1st-line therapy and treated with R-CHOP, 43% were treated with the two-weekly schedule (R-CHOP-14) and 57% received the three-weekly schedule (R-CHOP-21). Both schedules were applied for median 6 cycles (range 2-8); less than 6 cycles were applied in 23% and 30% of pts, respectively. Pts were median 67 years (yrs) old (33% ≤ 60 yrs), 47% female, 28% presented with tumour stage I (Ann Arbor), 27% with stage IV and 64% with at least one co-morbidity. 37% pts were of low risk (International Prognostic Index, IPI). Pts treated with the R-CHOP-14 or R-CHOP-21 differed in gender (female: 42% vs. 50%), performance status (ECOG 0: 44% vs. 40%) and pre-existing co-morbidities (60% vs. 67%), with no difference in age. Pts treated with R-CHOP-14 were diagnosed less often with tumour stage I (22% vs. 33%). Data on the application of Granulocyte colony-stimulating factor (G-CSF) were available for 381 pts. G-CSF was applied in 98% of pts treated with R-CHOP-14 and 61% of pts treated with R-CHOP-21. Pts treated with R-CHOP-21 and G-CSF were older (median 68 vs. 61yrs) than pts treated with R-CHOP-21 and no application of G-CSF. Objective response rate (ORR) as assessed by the local site was: 98% for R-CHOP-14 and 94% for R-CHOP-21; the clinical (unconfirmed) complete remission rate (CRu) was 65% for R- CHOP-14 and 70% for R-CHOP-21 (p=0.32). After a median follow-up of 22 months (maximum 51 months), 2-year progression-free survival rate (PFS) is 74% (1-year: 84%) for R-CHOP-14 and 82% (1-year: 85%) for R-CHOP-21. 2-year overall survival rate (OS) is 86% (1-year: 91%) for R-CHOP-14 and 85% (1-year: 89%) for R-CHOP-21. At time of analysis, 9% of pts (R-CHOP-14) and 8% (R-CHOP-21) have received a 2nd-line therapy. Overall, 7% of pts have been lost to follow-up. At this point, the high rate of pts alive without progression (〉80%) precluded multivariate regression analyses regarding factors affecting PFS or OS. Conclusion Our data show that in routine practice, independent of age, pts with good performance status and low burden of co-morbities are more likely to receive the dose-dense two-weekly R-CHOP-14 schedule than the three-weekly R-CHOP-21 schedule as 1st-line treatment. First outcome data show that the effectiveness (ORR, PFS and OS) of both schedules is similar despite the differences in pts selection. DLBCL: Diffuse Large B-cell Lymphoma References: Cunningham et al., The Lancet. Mai 2013;381(9880):1817–26 │ Ohmachi K et al., Ann Oncol. 2011;22(6):1382–91 │ Pfreundschuh M et al., Blood. 2004;104(3):634–41 Disclosures No relevant conflicts of interest to declare.

Description: Introduction: Poor adherence and persistence to anticancer treatment are serious issues in the management of cancer patients since nonadherence has been shown to lead to higher treatment failure rates, worse outcome and higher total costs of care. The combination of the proteasome inhibitor carfilzomib (Kyprolis®) with lenalidomide (Revlimid®) and dexamethasone (CAR/LEN/DEX) or with dexamethasone alone (CAR/DEX) is approved for the treatment of patients with multiple myeloma who have received at least one prior therapy. According to the current approved schedule, carfilzomib has to be given twice weekly in both regimens. Real-world data on the implementation of this treatment recommendation are still limited. Methods: The prospective, multicenter, non-interventional, observational CARO study was designed to collect data on 300 patients with multiple myeloma (CAR/LEN/DEX: 200, CAR/DEX: 100) from 90 sites across Germany. Primary objective is patients' adherence and persistence to carfilzomib therapy as prescribed by the treating physician according to current Summary of Product Characteristics (SmPC). Secondary objectives are patients' adherence and persistence to lenalidomide and dexamethasone as well as the real-world implementation of the recommended CAR/LEN/DEX or CAR/DEX dosing regimen in clinical routine (i.e., the comparison of actually administered medication versus recommended medication according to current SmPC). Exploratory objectives are effectiveness, safety and health-related quality of life. The first interim analysis of the CARO study was scheduled to assess the primary and secondary endpoints 12 months after the recruitment of the first patient. Results: Between October 2016 and October 2017, 102 patients had been enrolled, thereof 68 patients into the CAR/LEN/DEX cohort and 32 patients into the CAR/DEX cohort at the time of the pre-specified interim analysis (database cut: 25 October 2017). Here, the focus is on the adherence of the twice weekly carfilzomib schedule in evaluable patients who received CAR/LEN/DEX (N=64) and on the implementation of the SmPC in terms of timing, dosing and frequency. Median age of patients was 72.3 years (range 43.4-84.3), 45.3% were female and 70.3% of the patients had a good performance status (PS) with a Karnofsky PS score of 80 to 100. The relative mean dose intensity of carfilzomib was 88.1%. 1368 of the scheduled 1591 carfilzomib administrations (86.0%) were given in time. 7.9% (n=125) of administrations were omitted, 5.0% (n=80) of administrations were delayed and 1.1% (n=18) of doses were administered earlier. Carfilzomib was omitted at least once in 43.8% of patients (n=28). 62.5% (n=40) and 18.8% (n=12) of patients, respectively, had a delayed or earlier carfilzomib administration documented at least once during their course of treatment. Reasons for deviations from the recommended carfilzomib dosing schedule concerning timing are depicted in Table 1. 1328 of 1466 carfilzomib administrations (90.6%) were given at the recommended dose. 6.2% (n=91) of doses were reduced. The main reason for dose reduction was the occurrence of adverse events (4.0%, n=58). Other reasons were: nonadherence (1.2%, n=18), organizational reasons (0.1%, n=2) and others (0.9%, n=13). 23.4% (n=15) of patients received at least one reduced carfilzomib dose during their course of treatment. The mean adherence to the carfilzomib dosing regimen (i.e., the percentage of doses administered as scheduled by the treating physician and not modified for adherence reasons) was 94.8%. Conclusion: According to our interim results, 86% of carfilzomib administrations were given in time and more than 90% of administrations were given at the recommended dose. Deviations from the recommended carfilzomib regimen were mainly due to safety issues or organizational reasons, but not due to nonadherence. Carfilzomib treatment adherence was almost 95%. Though, despite the required twice weekly dosing schedule, the carfilzomib regimen seems to be a convenient treatment option for multiple myeloma patients. Results have to be confirmed at final analysis. Disclosures Knauf: Celgene: Consultancy, Honoraria; Roche: Consultancy; Amgen: Consultancy, Honoraria; Mundipharma: Consultancy; Gilead Sciences: Consultancy; AbbVie: Consultancy; Janssen: Consultancy. Marschner:Amgen: Consultancy, Honoraria; IOMEDICO: Employment, Equity Ownership; Sandoz: Honoraria.

Description: Introduction Recent data from phase III clinical trials showed that in previously untreated patients (pts) with indolent (low-grade) non-Hodgkin’s lymphoma (iNHL) bendamustine plus rituximab (BR) resulted in superior progression-free survival (STiL NHL 1-2003) and non-inferior response rates (STiL NHL 1-2003 and BRIGHT) compared to R-CHOP. Since clinical trials are restricted to highly selected pts, we here investigated effectiveness of BR and R-CHOP in unselected pts treated in routine practice by German office-based haematologists. Methods The open, longitudinal, multicentre, clinical registry on lymphoid neoplasms (TLN Registry, ClinicalTrial.gov registry NCT00889798) prospectively collects data on the treatment of pts with lymphoid B-cell neoplasms as administered by a network of German office-based haematologists. Pts are followed for 5 years. A broad set of data regarding patient and tumour characteristics, comorbidities, all systemic treatments and response rates, progression-free survival and overall survival are recorded. Automated plausibility and completeness checks with subsequently generated queries by the electronic data capture system ensure data reliability. In addition, data managers regularly check for plausibility and issue queries. Since May 2009, 111 sites have recruited a total of 2897 pts. Results 633 pts with iNHL (52% follicular, 13% mantle cell lymphoma), recruited at the onset of their 1st-line therapy and treated with BR (82%) or R-CHOP (18%), were included in this analysis. The choice of the regimen was upon the decision of the treating physician in accordance with the patient´s informed consent. Pts were median 69 years (yrs) old (range 24-93 yrs), 54% were male, 55% had tumour stage IV (Ann Arbor), 24% presented with B symptoms, 25% with bulky disease, and 61% with at least one comorbidity. Clinical and tumour characteristics differed between pts receiving BR or R-CHOP: Pts treated with BR were older (median 70 vs. 61 yrs; p

Description: Introduction Fludarabine, cyclophosphamide, rituximab (FCR) is currently considered the standard of care for medically fit patients (pts) with untreated chronic lymphocytic leukaemia (CLL). However, due to its significant haematological toxicity other, potentially less toxic regimens are currently under investigation. Results of the phase III trial CLL 10 of the German CLL-Study Group (GCLLSG) comparing FCR to bendamustine, rituximab (BR) are eagerly awaited. Since clinical trials are restricted to highly selected pts, we here investigated effectiveness of BR and FCR in unselected pts with CLL treated in routine practice by German office-based haematologists. Methods The open, longitudinal, multicentre, clinical registry on lymphoid neoplasms (TLN Registry, ClinicalTrial.gov registry NCT00889798) prospectively collects data on the treatment of pts with lymphoid B-cell neoplasms as administered by a network of German office-based haematologists. Pts are followed for 5 years. A broad set of data regarding patient and tumour characteristics, comorbidities, all systemic treatments and response rates, progression-free survival and overall survival are recorded. Automated plausibility and completeness checks with subsequently generated queries by the electronic data capture system ensure data reliability. In addition, data managers regularly check for plausibility and issue queries. Since May 2009, 111 sites have actively recruited a total of 2897 pts. Results 381 pts with CLL, recruited at the onset of their 1st-line therapy and treated with BR (69%) or FCR (31%), were included in this analysis. The choice of the regimen was upon the decision of the treating physician in accordance with the patient´s informed consent. Pts are median 70 years (yrs) old (range 21-90 yrs), 68% male, 42% have Binet stage C, 27% present with B symptoms, 13% with bulky disease and 66% with at least one comorbidity. Clinical and tumour characteristics differ between pts receiving BR or FCR: Pts treated with BR are older (median 71 vs. 65 yrs; p

Description: Abstract 4605 Introduction With the FDA and EMA approval of Bendamustine and Rituximab new treatment options have recently become available to patients (pts) with chronic lymphocytic leukemia (CLL). Clinical registries provide insight into real-life treatment of pts. They can help to answer the question whether patients may benefit from new research findings. Methods The clinical registry on lymphoid neoplasms (TLN Registry), conducted by iOMEDICO in collaboration with the Arbeitskreis Klinische Studien (AKS) and the Kompetenznetz Maligne Lymphome (KML), prospectively collects data on the treatment of pts with lymphoid B-cell neoplasms as administered in hematology outpatient centres in Germany. Pts are followed for 5 years. A broad set of data regarding patient and tumor characteristics, comorbidities, all systemic treatments, response rates, progression-free survival and overall survival are recorded. Since May 2009, 106 sites have actively recruited a total of 2579 pts. Results From the overall sample, 420 pts received systemic 1st-line treatment for CLL. 65% of pts are male, mean age at time of primary diagnosis was 66 years (yrs) and at start of therapy 69 yrs. Tumor stage was 20% Binet A, 35% Binet B and 45% Binet C. 68% of pts (n=285) were diagnosed with at least one comorbidity, mainly hypertension (37%) or diabetes (15%); the average Charlson Comorbity Index of 0.7 indicates that overall pts have few comorbities. Rituximab is part of the 1st-line treatment in 82% (n=345) of pts with CLL. Bendamustine is part of the 1st-line treatment in 59% (n=247) of pts with CLL. It is mostly applied in combination with Rituximab (BR, 51%, n=213). Further 7% (n=28) receive Bendamustin as monotherapy. Fludarabine is part of the 1st-line treatment in 31% (n=132) of pts with CLL. It is applied in combination with Cyclophosphamide and Rituximab (FCR, 25%, n=103), as monotherapy (4%, n=15) or in combination with Cyclophosphamide (FC, 1%, n=6). Chlorambucil is part of the 1st-line treatment in 7% (n=31) of pts with CLL. It is applied as monotherapy (4%, n=15) or in combination with Rituximab (2%, n=10). Pts receiving BR, FCR or Chlorambucil differ. Pts characteristics indicate that BR and Chlorambucil are applied preferably in elderly pts (mean 70.1 (BR) vs. 75.7 (Chlorambucil) vs. 63.4 (FCR) yrs). Also, BR is given preferably in advanced stages of the disease as compared to FCR (Binet C 49% vs. 34%). The use of BR has increased from 41% in 2009 to 57% in 2011, while the use of FCR has decreased from 33% in 2009 to 17% in 2011. Of all pts with CLL in the TLN, 181 have received 2nd-line treatment. Rituximab is part of the 2nd-line treatment in 76% (n=137) of pts with CLL. Bendamustine is part of the 2nd-line treatment in 66% (n=120) of pts with CLL. It is mostly applied in combination with Rituximab (BR, 56%, n=101). Further 10% (n=18) receive Bendamustin as monotherapy. Fludarabine is part of the 2nd-line treatment in 20% (n=37) of pts with CLL. It is applied in combination with Cyclophosphamide and Rituximab (FCR, 10%, n=18), as monotherapy (5%, n=9) or in combination with Cyclophosphamide (FC, 3%, n=5). Chlorambucil is part of the 2nd-line treatment in 4% (n=7) of pts with CLL. It is mostly applied in combination with Rituximab (2%, n=4). Conclusion Rituximab and Bendamustine are the most frequently used drugs for the treatment of CLL in German hematology outpatient centres. The use or BR has significantly increased since 2009. In contrast, the use of FCR has decreased and only a minority of pts receive Chlorambucil. This indicates that in Germany Chlorambucil is no longer considered the “standard of care” for elderly pts with CLL. These data also show that results from clinical trials are quickly implemented into daily practice. The impact of these new treatment options on quality of life and survival remains to be of central interest in the future. Disclosures: Knauf: Mundipharma GmbH: Honoraria, Membership on an entity's Board of Directors or advisory committees.