Real-world treatment patterns in patients initiating third-line therapy for relapsed or refractory multiple myeloma in Germany, Italy, the United Kingdom, France, and Spain.

OBJECTIVES: To retrospectively analyze real-world treatment patterns in patients with relapsed/refractory multiple myeloma (RRMM) who initiated third-line treatment in Europe. METHODS: German and Italian administrative claims data were sourced from the German AOK PLUS health insurance fund and Italian local health units (2016-2020). Data for the United Kingdom (UK), France, and Spain were sourced from medical chart reviews (MCRs) from 2016 to 2018 (historical) and 2019 to 2021 (new) using electronic case report forms. RESULTS: Across all countries, immunomodulatory imide drug (IMiD)-based regimens were prominent in the third-line setting. From 2016 to 2020, lenalidomide-dexamethasone was most common in Italy (18.0%) and Germany (12.7%). From 2019 to 2021, the most common regimen was ixazomib-lenalidomide-dexamethasone (67.5%) in the UK, pomalidomide-dexamethasone (17.1%) in France, and daratumumab-bortezomib-dexamethasone (15.0%) in Spain. In the historical data (2016-2018), third-line lenalidomide- and pomalidomide-dexamethasone doublet use across the UK (>47%), France (>46%), and Spain (>33%) was high. From historical to new, triplet use increased in Spain (>19% to >60%) as did anti-CD38 agent use in France (15.1% to 51.9%) and Spain (19.7% to 42.1%). CONCLUSIONS: From 2016 to 2021, third-line regimens were mostly IMiD based. The MCR data demonstrated evolving treatment choices from 2016 to 2018 and 2019 to 2021, providing insights into uptake of novel agents and current RRMM European clinical practice.

Diagnosis and treatment of multiple myeloma in Germany: analysis of a nationwide multi-institutional survey.

A nationwide, multi-institutional survey was performed in 2011 and 2015 to analyze routine practice for myeloma patients outside clinical trials in Germany. We contacted university hospitals, community hospitals, and office-based hematologists in order to enter clinical data from newly diagnosed and relapsed patients into an online platform. Complete datasets were available for 478 (2011) and 515 (2015) patients. While median age at diagnosis increased from 70 to 72 years, patients had fewer concomitant diseases (2011 61%; 2015 51%) and presented with equal performance status (ECOG 0-1, 2011 66%; 2015 68%). Cytogenetic analysis was performed in 53% (2011) and 59% (2015). Patients ≥70 years, or patients with comorbidities who were no candidates for autologous transplantation (ASCT), were less frequently tested for cytogenetic abnormalities (p = 0.001, respectively). There were more candidates for ASCT ≥65 years in 2015 (57%) than in 2011 (27%). Bortezomib was used in 92% of transplant-eligible and 66% of transplant-ineligible patients as frontline therapy in 2015. Application of bortezomib and lenalidomide for the first relapse changed from 2011 (bortezomib 45%; lenalidomide 27%) to 2015 (bortezomib 28%; lenalidomide 54%). For the second relapse, application of lenalidomide decreased from 2011 (36%) to 2015 (23%). Pomalidomide entered treatment for the second relapse in 2015 (11% of patients). Taken together, we demonstrate that results from clinical trials are implemented into general practice in Germany.

Altered treatment of chronic lymphocytic leukemia in Germany during the last decade.

Chronic lymphocytic leukemia (CLL) is the most common subtype of adult leukemia in the western world. We here report a nationwide survey monitoring the treatment decisions concerning CLL patients in Germany in 2011 and compare treatment trends to sequential surveys performed previously during the last decade. The rate of patients diagnosed in early stages (Binet A/B) notably increased (2006: 66 %, 2009: 71 %, 2011: 77 %) over the years. From 2006 to 2009, the most frequent applied regime switched from chlorambucil to fludarabine containing regimes (2006 chlorambucil: 32 %, 2009: 14 %, fludarabine 2006: 23 %, 2009: 37 %). In 2011, the combination of rituximab with bendamustine (31 %) was most frequent used followed by the rituximab-fludarabine-cyclophosphamide (22 %) regime. Further, immune-chemotherapies were administered significantly more often over the observation period (2006: 15 %, 2011: 73 %). Taken together, this data reflects the change of treatment strategies over the last decade in clinical reality.

The impact of age on the diagnosis and therapy of myelodysplastic syndromes: results from a retrospective multicenter analysis in Germany.

Myelodysplastic syndromes (MDS) is a disease of predominantly elderly patients with a median age of >70 yrs. However, data on the management of these patients outside of clinical trials are scarce. To assess patterns of MDS management in routine patient care with regard to the impact of age, we conducted a multicenter, representative survey of MDS health services in Germany. Data of 269 patients treated at 57 institutions were collected from preplanned chart reviews and were analyzed retrospectively. At diagnosis, median age was 70 yrs, 50% of patients had a Karnofsky index (KI) of 90%, and 12% had a comorbidity index ≥ 3 according to Sorror et al. (J Clin Oncol, 25, 2007, 4246). Cytogenetic analysis and International Prognostic Scoring System (IPSS) risk assessment were performed significantly less frequently in patients >75 yrs than in patients ≤ 75 yrs (P < 0.001 and P = 0.019). In bivariate analysis, potential predictors for performing IPSS risk assessment were age ≤ 75 yrs (y/n, P = 0.019), diagnosis at a university hospital (y/n, P = 0.001), WHO subtypes RCUD (y/n, P = 0.028), RARS (y/n, P = 0.002), or RAEB II (y/n, P = 0.037). Patients ≤ 75 yrs were more likely to receive active therapies (i.e., chemotherapy, immunomodulatory therapy, or epigenetic therapy) than patients >75 yrs (51% vs. 37%, P = 0.007). In bivariate analysis age ≤ 75 yrs (y/n, P = 0.007) was a significant predictor for active treatment with no correlation with the other predictors [IPSS risk score int-2 or high (y/n, P = 0.005), WHO subtypes RCUD (y/n, P < 0.001), RCMD (y/n, P = 0.003), RAEB II (y/n, P < 0.001), or CMML I (y/n, P = 0.020)]. This survey confirms the impact of age on the thoroughness of MDS diagnosis and the decision for active treatment. As cytogenetic analysis and risk assessment are essential for the choice of appropriate therapy, elderly patients in particular may not be receiving adequate treatment.

Diagnosis and therapy of myelodysplastic syndromes in Germany: a retrospective multicenter analysis.

BACKGROUND: Myelodysplastic syndromes (MDS) are a heterogenous group of clonal hematopoietic stem cell disorders. PATIENTS AND METHODS: In order to assess current diagnosis and treatment patterns in Germany, the data of 269 patients with MDS from 57 representative centers were analyzed. RESULTS: The most common symptom leading to an initial diagnosis of MDS was anemia (79%). WHO classification, cytogenetic analysis, and IPSS scoring were performed in 92, 67, and 61% of patients, respectively. 5q deletions were identified in 34% of patients whose cytogenetic status was analyzed. Symptomatic anemia was the major trigger for initiating therapy. 49% of patients received supportive care only, and 49% received active therapy (i.e., chemo-, immunomodulatory, or epigenetic therapy), including 5% who received allogeneic transplantation. Of those patients treated with active therapy, approximately half of the higher-risk patients received azacitidine, and approximately half of the lower-risk patients received lenalidomide. Overall, 80% of patients received some form of supportive care, mainly red blood cell transfusions. CONCLUSION: While the WHO classification system is widely used in clinical practice, karyotyping and IPSS risk assessment do not seem to be common standard. Despite encouraging data on the use of effective and novel drugs, such as lenalidomide and azacitidine in MDS therapies, management of the disease could be further improved by more widespread use of risk stratification of patients using cytogenetics and IPSS assessment.

Adjusted Comparison of Outcomes between Patients from CARTITUDE-1 versus Multiple Myeloma Patients with Prior Exposure to PI, Imid and Anti-CD-38 from a German Registry.

Ciltacabtagene autoleucel (cilta-cel) is a Chimeric antigen receptor T-cell therapy with the potential for long-term disease control in heavily pre-treated patients with relapsed/refractory multiple myeloma (RRMM). As cilta-cel was assessed in the single-arm CARTITUDE-1 clinical trial, we used an external cohort of patients from the Therapie Monitor registry fulfilling the CARTITUDE-1 inclusion criteria to evaluate the effectiveness of cilta-cel for overall survival (OS) and time to next treatment (TTNT) vs. real-world clinical practice. Individual patient data allowed us to adjust the comparisons between both cohorts, using the inverse probability of treatment weighting (IPW; average treatment effect in the treated population (ATT) and overlap population (ATO) weights) and multivariable Cox proportional hazards regression. Outcomes were compared in intention-to-treat (HR, IPW-ATT: TTNT: 0.13 (95% CI: 0.07, 0.24); OS: 0.14 (95% CI: 0.07, 0.25); IPW-ATO: TTNT: 0.24 (95% CI: 0.12, 0.49); OS: 0.26 (95% CI: 0.13, 0.54)) and modified intention-to-treat (HR, IPW-ATT: TTNT: 0.24 (95% CI: 0.09, 0.67); OS: 0.26 (95% CI: 0.08, 0.84); IPW-ATO: TTNT: 0.26 (95% CI: 0.11, 0.59); OS: 0.31 (95% CI: 0.12, 0.79)) populations. All the comparisons were statistically significant in favor of cilta-cel. These results highlight cilta-cel's potential as a novel, effective treatment to address unmet needs in patients with RRMM.

How to treat multiple myeloma - a representative multicentre treatment survey.

BACKGROUND: The present survey was undertaken to gain insights in the changes of disease management of multiple myeloma (MM) over time and the implementation of new guidelines into daily practice. PATIENTS AND METHODS: Diagnosis and treatment of MM were evaluated based on a 3-month representative multicentre survey including 386 patients from 35 centres in Germany in 2008. The results were compared to similar surveys in 2004 and 2006. RESULTS: At the time of first diagnosis, most patients (62.5%) were already in stage III (Durie-Salmon). The presence of deletion 13q was determined in 22% of patients only. However, determination of other prognostic factors has become increasingly well established. These include the levels of ß2-microglobulin and serum albumin, each of which was determined in more than 2/3 of patients. Overall, 35% of patients were considered for high-dose chemotherapy. As a consequence of the development of innovative substances, there are remarkable shifts in first line, second line, and third line therapy with an increase in the use of bortezomib at all levels of therapy. CONCLUSIONS: Regarding diagnostic measures, deviations from recommended guidelines became evident. Also, high-dose chemotherapy with stem cell support was considered in a minority of patients only. Novel substances, however, were rapidly integrated into the treatment of MM.

Diagnostic and therapeutic approaches to multiple myeloma patients: 'Real-world' data from representative multicentre treatment surveys in Germany between 2008 and 2011.

A survey was conducted to investigate the standard of care for multiple myeloma in Germany, in order to clarify the status of implementation of international and national treatment guidelines. In addition, the changes in disease management over time were investigated by comparison with surveys conducted in 2008 and 2009. The survey captured a representative sample of 478 myeloma patients with a mean age of 67.9 years across various stages of the disease. Diagnostic approaches, prognostic aspects and treatment decisions were evaluated based on a survey conducted in 2011 in 58 representative centres in Germany, including university and non-university hospitals and office-based haematologists. Data were collected from chart reviews and were analysed retrospectively. Over time, an increasing number of patients were investigated for cytogenetic abnormalities (53%). Age <69 years and lack of comorbid conditions were major determinants for cytogenetic testing. Bortezomib/chemotherapy-based regimens have become the preferred first-line treatments independent of planning autologous blood stem cell transplantation (ASCT) in first-line therapy. Thalidomide- and lenalidomide-based combination therapies are typically used as second-line treatments in 31% of patients. Compared with previous reviews, the frequency of ASCT was stable, at ~30% of patients. Younger age and indicators of more severe disease, such as the presence of CRAB criteria, influenced the decision in favour of performing ASCT. Compared to previous surveys, the requirement for erythropoietin and granulocyte colony-stimulating factor, as well as transfusions of red blood cells and platelets, respectively, have decreased considerably. In summary, novel agents have led to a substantial change in the first-line and relapsed treatment approaches. Age and comorbidities remain major factors influencing treatment decisions, but cytogenetic testing to investigate myeloma-related risk profiles is increasingly integrated. The use of novel agents has affected supportive care, with reduced necessity for substitute blood products and reduced administration of bone marrow-stimulating factors.

Trastuzumab in Esophagogastric Cancer: HER2-Testing and Treatment Reality outside Clinical Studies in Germany.

We analysed trends over time in palliative first-line chemotherapy in patients with locally advanced or metastatic esophagogastric cancer. Special focus was on frequency and quality of HER2-testing and trends in drug use in combination with trastuzumab. Earlier published data about patients treated outside clinical studies showed a relatively low rate of HER2-testing and insufficient test quality. A total of 2,808 patients retrospectively documented in Therapiemonitor (®) from 2006 to 2013 were analysed regarding treatment intensity and trends in used drugs. Data on HER2-testing and therapies were analysed in two cohorts documented in 2010 and 2011 (1) compared to 2012 and 2013 (2). Treatment intensity increased: 49.3% of patients received at least a triplet in 2013 compared to 10.1% in 2006. In cohort 2 HER2 expression was tested in 79.1% of the cases. Still, in 26.9% testing was not done as requested by guidelines. Good performance status, multiple metastases, age ≤ 65 years, the objective "to prevent progression," good cognitive capabilities, estimated good compliance, and social integration positively influenced the probability of HER2-testing; comorbidities negatively affected it. Usage of the combination of fluoropyrimidines and cisplatin with trastuzumab declined from 67% in cohort 1 to 50% in cohort 2.

Cost-effectiveness of rituximab in addition to fludarabine and cyclophosphamide (R-FC) for the first-line treatment of chronic lymphocytic leukemia.

The cost-effectiveness of rituximab in combination with fludarabine/cyclophosphamide (R-FC) for the first line treatment of chronic lymphocytic leukemia (CLL) was evaluated. Based on long-term clinical data (follow-up of 5.9 years) from the CLL8-trial, a Markov-model with three health states (Free from disease progression, Progressive disease, Death) was used to evaluate the cost per quality-adjusted life-year (QALY) and cost per life years gained (LYG) of R-FC from the perspective of the German statutory health insurance (SHI). The addition of rituximab to FC chemotherapy results in a gain of 1.1 quality-adjusted life-years. The incremental cost-effectiveness ratio (ICER) of R-FC compared with FC was €17,979 per QALY (€15,773 per LYG). Results were robust in deterministic and probabilistic sensitivity analyses. From the German SHI perspective, rituximab in combination with FC chemotherapy represents good value for first-line treatment of patients with CLL and compares favorably with chemotherapy alone.

Changes in the diagnosis and treatment of patients with low grade lymphoma in Germany: years 2006-2009.

Today's treatment options for indolent lymphoma and chronic lymphocytic leukemia (CLL) range from watch & wait, immunochemotherapy up to allogeneic transplantation. We describe changes in the diagnosis and treatment of indolent lymphoma and CLL in Germany between 2006 and 2009. Two nation-wide surveys in the fourth quarter of 2006 and 2009 included patients with indolent lymphoma and CLL. Data from 576 patients from 46 centers in Q4/2006 were compared with data from 521 patients from 57 centers in Q4/2009. The subpopulation of patients ≥ 70 years of age and the number of patients with comorbidities increased from 39% to 55% and 47% to 55%, respectively. Both in indolent lymphoma and CLL, Rituximab and R-based immunochemotherapy (50.6% vs. 64.4%) as well as bendamustine (4.8 % vs. 24%) were much more frequently applied. In contrast, high dose chemotherapy consolidation was almost abandoned in first line treatment. Supportive care is given more frequently, with exception of erythropoietin and immunoglobulins. Our national survey confirmed that scientific results were rapidly transferred into clinical care of indolent lymphoma.

[Deficits in management of patients with colorectal carcinoma in Germany. Results of multicenter documentation of therapy algorithms]. / Defizite in der Behandlung von Patienten mit kolorektalem Karzinom in Deutschland. Ergebnisse einer multizentrischen Dokumentation von Therapiealgorithmen.

BACKGROUND: Adjuvant chemotherapy for patients with UICC III (Dukes C) colorectal cancer (consensus statements NIH 1990, German Cancer Society 1994) and palliative chemotherapy for metastatic disease have long been recognized to provide a survival benefit in colorectal cancer. However, it remains unclear if these concepts have made inroads into clinical practice. PATIENTS AND METHODS: Therefore, we asked 74 institutions treating colorectal cancer patients in Germany to document the treatment algorithms of all patients with colorectal cancer seen in the third quarter of 1998. Clinical careers of 1,001 patients (m/f 465/536; median age 62.9 years [28-93]; colon 596, rectum 405; UICC I 117, II 206, III 407, IV 218) were documented. RESULTS: Only 63.4% of patients with UICC III colorectal cancer received adjuvant therapy with a significant difference between hospitals with (67.1%) and without (42.6%) oncological departments (p < 0.01). Higher age appeared to be the most important factor for withholding treatment since 196 of 286 (68.5%) patients < 70 years, but only 57 of 121 (47.1%) > 70 years underwent adjuvant therapy. 78.4% of patients with UICC IV colorectal cancer (91.8% university hospitals, 76.8% hospital with, 50% without oncological departments, 66.7% rehabilitation clinics, 82.4% private practices) received palliative chemotherapy (first line: 5-FU/FA bolus 57%, 5-FU/FA infusion 20%, 5-FU mono 15%). CONCLUSION: Considering an annual incidence of colorectal cancer in Germany of 52,000 with 30% UICC III, discounting patients > 80 years or ECOG status > 2, and estimating a survival benefit of 10% after adjuvant chemotherapy, approximately 530 lifes are lost annually in Germany due to insufficient treatment of UICC III colorectal cancer based on our survey. In addition, substantial financial demand is generated by the subsequent palliative treatment of potentially curable patients.--In conclusion, survey-based analysis of treatment algorithms can provide valuable insights into clinical practice in oncology and can disclose deficits in patient care as demonstrated here in colorectal cancer.

Metastatic esophagogastric adenocarcinoma: trends in first-line treatment and predictive factors for the implementation of HER2 testing in clinical practice during the first year after trastuzumab market approval.

PURPOSE: Little is known about the use of first-line chemotherapy in clinical practice in patients with advanced esophagogastric adenocarcinoma, and no data have been published regarding potential obstacles for the implementation of molecular testing for targeted agents in this patient group. Here, we sought to evaluate factors influencing treatment decisions with special focus on the implementation of HER2 testing during the first year after trastuzumab market approval in Germany. METHODS: A total of 754 patients undergoing treatment decisions for palliative first-line therapy in 2010 were documented using Therapiemonitor(®). Drug use and intensity of first-line treatment were analyzed. Data on HER2 testing and test algorithm are described, and variables influencing HER2 testing were selected using bivariate analysis. Significant factors were included in a multivariate logistic regression analysis. RESULTS: Compared with previous years, treatment intensity has further increased. The use of chemotherapy triplets rose from 10.1 % in 2006 to 60.3 % in 2010. In 2010, 49.1 % of patients were tested for HER2 and in 52.2 % of these patients the currently proposed test algorithm was used. Using multivariate logistic regression analysis age ≥67 years and "initiating institution: practice" were found to negatively impact the likelihood of HER2 testing, while treatment goal "prevention of progression", multiple metastases and a Karnofsky status >80 % showed positive correlation with HER2 testing. CONCLUSION: The tendency to use more intensive first-line chemotherapy regimens in patients with advanced esophagogastric adenocarcinoma continued in 2010. Only a minority of patients had an access to the appropriate molecular diagnostics and therefore to treatment with trastuzumab. The access was limited due to the preselection following individual, clinical and institutional factors.

Treatment of indolent lymphoma in Germany - results of a representative population-based survey.

BACKGROUND: In advanced-stage indolent lymphoma, therapeutic approaches may vary from watch and wait, antibody monotherapy, immunochemotherapy, or dose-intensified consolidation up to allogeneic strategies. In this nationwide survey, representative hematologic/oncologic centers monitored current treatment strategies in indolent lymphoma in general practice. METHODS: Four hundred ninety-five centers involved in the treatment of indolent lymphoma including university hospitals, community hospitals, and oncologists in practice were identified and contacted. Thirteen percent of centers provided information on 741 patients, which corresponds to 10% of the expected national prevalence. Detailed data on 576 unselected patients from 46 representative centers (2 university hospitals, 25 community hospitals, and 19 oncologists in practice) for whom a treatment decision took place in the fourth quarter of 2006 (start, change, or end of therapy) were included in this analysis. Data were verified by monitoring the pseudonymized patient documents. RESULTS: Median age was 67 years (range, 17 to 95 years) and 65% of patients were 60 years of age or older. Concomitant disease was frequent with cardiac disease (29%), hypertension (28%), diabetes (11%), and renal impairment (7%) being the most typical combinations. Histologies included 39% follicular lymphoma, 26% chronic lymphocytic leukemia (CLL), 10% marginal zone, 9% mantle cell lymphoma (MCL), and 16% other. Only 10% of the overall patient population were treated within these studies. The aim of initial therapy was curative in 35%, and physicians aimed at improved survival in 62% and palliation only in 54% of patients. Radiation (10%), antibody monotherapy (4%), chemotherapy (33%), and combined immunochemotherapy (31%) were the most frequent approaches. Applied chemotherapies included cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) (46%), fludarabine combinations (F/FC/FCM: 15%), chlorambucil (14%), CVP/COP (9%) and bendamustin (4%). Maintenance was used in 12% and autologous/allogeneic stem cell consolidation were rarely applied (both in 3% of patients). At first relapse, combined approaches including immunochemotherapy (49%), maintenance therapy (16%), and autologous/allogeneic transplantation (14%/4%) were more frequently administered. As expected, different treatment strategies and response rates were observed in follicular lymphoma (FL), MCL, and CLL. Interestingly, supportive measures including antibiotics (34%), erythrocyte transfusions (32%), granulocyte colony-stimulating factor (22%), immunoglobulines (19%), antifungal drugs (13%), and erythropoetin (10%) were frequently applied even in first-line therapy. Overall response was 83% (FL: 97%, MCL: 95%, CLL: 74%) with a 39% complete response (FL 63%, MCL 54%, CLL 15%) rate. DISCUSSION: In this population-based survey, patients characteristics differed significantly from published study cohorts as did clinical strategies and therapeutic approaches. Thus, clinically more relevant studies in medically compromised patients are urgently warranted.