Molecular Long-Term Analysis of the GMMG-HD4 Trial in Multiple Myeloma-Patterns of Association of Chromosomal Aberrations with Response and Proliferation Determining Survival in Selecting Treatments in View of Limited Resources in Low- and Middle-Income Countries.

Based on the lack of differences in progression-free and overall survival after a median follow-up of 93 months in our HOVON-65/GMMG-HD4 trial (German part; n = 395) randomizing VAD induction (vincristin/adriamycin/dexamthasone)/tandem-transplantation/thalidomide-maintenance vs. PAD induction (bortezomib/adriamycin/dexamethasone)/tandem transplantation/bortezomib maintenance, we discern how chromosomal aberrations determine long-term prognosis by different patterns of association with proliferation and treatment-dependent response, whether responses achieved by different regimens are equal regarding prognosis, and whether subpopulations of patients could be defined as treatable without upfront "novel agents" in cases of limited resources, e.g., in low- or middle-income countries. Serum parameters and risk factors were assessed in 395 patients. CD138-purified plasma cells were subjected to fluorescence in situ hybridization (n = 354) and gene expression profiling (n = 204). We found chromosomal aberrations to be associated in four patterns with survival, proliferation, and response: deletion (del) del17p13, del8p21, del13q14, (gain) 1q21+, and translocation t(4;14) (all adverse) associate with higher proliferation. Of these, del17p is associated with an adverse response (pattern 1), and 1q21+, t(4;14), and del13q14 with a treatment-dependent better response (pattern 2). Hyperdiploidy associates with lower proliferation without impacting response or survival (pattern 3). Translocation t(11;14) has no association with survival but a treatment-dependent adverse response (pattern 4). Significantly fewer patients reach a near-complete response or better with "conventional" (VAD) vs. bortezomib-based treatment after induction or high-dose melphalan. These patients, however, show significantly better median progression-free and overall survival. Molecularly, patients responding to the two regimens differ in gene expression, indicating distinct biological properties of the responding myeloma cells. Patients with normal renal function (89.4%), low cytogenetic risk (72.5%), or low proliferation rate (37.9%) neither benefit in progression-free nor overall survival from bortezomib-based upfront treatment. We conclude that response level, the treatment by which it is achieved, and molecular background determine long-term prognosis. Chromosomal aberrations are associated in four patterns with proliferation and treatment-dependent responses. Associations with faster and deeper responses can be deceptive in the case of prognostically adverse aberrations 1q21+ and t(4;14). Far from advocating a return to "outdated" treatments, if resources do not permit state-of-the-art-treatment, normal renal function and/or molecular profiling identifies patient subpopulations doing well without upfront "novel agents".

Pomalidomide plus dexamethasone for patients with relapsed or refractory multiple myeloma: Final results of the non-interventional study POSEIDON and comparison with the pivotal phase 3 clinical trials.

BACKGROUND: Prognosis of patients with multiple myeloma (MM) who have relapsed on or become refractory to immunomodulators and bortezomib is poor, and treatment options are limited. While pomalidomide plus low-dose dexamethasone (POM/DEX) has demonstrated efficacy in clinical trials, real-world evidence is scarce. PATIENTS AND METHODS: POSEIDON was a prospective non-interventional study designed to evaluate effectiveness, safety and quality of life (QoL) of POM/DEX in patients with relapsed or refractory MM (R/RMM) pretreated with at least two prior therapy lines including both lenalidomide and bortezomib in real world in Germany. Patients received POM/DEX according to physicians' choice. Data were analyzed descriptively. RESULTS: Between 2014 and 2017, 151 patients were enrolled, 144 patients with a median of three prior therapy lines qualified for effectiveness analysis. Median age was 73.2 years. Median progression-free and overall survival were 6.3 months [95% confidence interval (CI) 5.2, 8.6] and 12.9 months [95% CI 10.6, 15.1]. Most frequent grade 3/4 adverse events were leukopenia (8.2%), pneumonia (7.5%) and anemia (5.5%). QoL was maintained after start of POM/DEX. CONCLUSION: The results of POSEIDON support the effectiveness and safety of POM/DEX in R/RMM patients pretreated with lenalidomide and bortezomib and highlight the clinical value of the POM/DEX regimen in the real-world setting. Registered at clinicaltrials.gov (NCT02075996).

Rare lymphomas in routine practice - Treatment and outcome in marginal zone lymphoma in the prospective German Tumour Registry Lymphatic Neoplasms.

Owing to its heterogeneity and rarity, management of disseminated marginal zone B-cell lymphoma (MZL) remains largely understudied. We present prospective data on choice of systemic treatment and survival of patients with MZL treated in German routine practice. Of 175 patients with MZL who had been documented in the prospective clinical cohort study Tumour Registry Lymphatic Neoplasms (NCT00889798) collecting data on systemic treatment, 58 were classified as extranodal MZL of mucosa-associated lymphoid tissue (MALT) and 117 as non-MALT MZL. We analyzed the most commonly used first-line and second-line chemo(immuno)therapies between 2009 and 2016 and examined objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and prognostic factors for survival. Compared to patients with MALT MZL, those with non-MALT MZL more often presented with bone marrow involvement (43% vs. 14%), Ann Arbor stage III/IV (72% vs. 57%) and were slightly less often in good general condition (ECOG = 0; 41% vs. 47%). In German routine practice, rituximab-bendamustine for a median of 6 cycles was the most frequently used first-line (76%) and second-line treatment (36%), with no major differences between MZL subtypes. The ORR for patients encompassing any positive response was 81%. For patients with MALT and non-MALT MZL, respectively, 5-years PFS was 69% (95% CI 52%-81%) and 66% (95% CI 56%-75%), 5-years OS 79% (95% CI 65%-89%) and 75% (95% CI 66%-83%). Cox proportional hazards models showed a significantly increased risk of mortality for higher age in all patient groups. Our prospective real world data give valuable insights into the management and outcome of non-selected patients with MZL requiring systemic treatment and can help optimize therapy recommendations.

Rare lymphomas in routine practice-Treatment and outcome in Waldenström's macroglobulinaemia in the prospective German Tumour Registry Lymphatic Neoplasms.

Waldenström's macroglobulinaemia (WM) is a rare indolent B-cell lymphoma for which only little prospective phase III evidence exists. Thus, real world data are important to provide insight into treatment and survival. We present here data on choice and outcome of systemic treatment of patients with WM treated in German routine practice. In total, 139 patients with WM who had been documented in the prospective clinical cohort study Tumour Registry Lymphatic Neoplasms (NCT00889798) were included into this analysis. We analysed the most frequently used first-line and second-line treatments between 2009 and 2017 and examined best response, progression-free survival (PFS) and overall survival (OS). Bendamustine plus rituximab, with a median of six cycles, was by far the most frequently used first-line treatment (81%). Second-line treatment was more heterogenous and mainly based on bendamustine, cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP), fludarabine or ibrutinib, the latter approved in 2014. Three-year PFS from start of first-line treatment was 83% (95% confidence interval [CI] 74%-88%), 3-year OS was 87% (95% CI 80%-92%). These prospective data give valuable insights into the management and outcome of non-selected patients with WM treated in German routine practice. In the lack of prospective phase III clinical trials, real world data can help bridging the gap of evidence.

Real-world treatment patterns and outcomes in non-transplant newly diagnosed multiple Myeloma in France, Germany, Italy, and the United Kingdom.

OBJECTIVES: The treatment paradigm in newly diagnosed multiple myeloma (NDMM) is evolving toward individualized, risk-directed, and longer duration of therapy (DOT). The objective of this study was to describe treatment patterns and outcomes in non-transplant NDMM in four European countries. METHODS: This retrospective chart review included adults with NDMM diagnosed between January 1, 2012, and December 31, 2013 (early cohort), or April 1, 2016, and March 31, 2017 (recent cohort). RESULTS: Among 836 patients, molecular testing was performed in 21% and 35% patients of early vs recent cohorts; proteasome inhibitor (PI)/alkylator combinations were the principal first-line (1 L) therapy (39% vs 43%). Use of immunomodulatory drug (IMID)/alkylator combinations declined from early to recent cohort (26% vs 13%) but IMID (7% vs 16%) use increased. Few patients (5%) received 1 L maintenance therapy. Two-thirds of patients were treated with a fixed duration intent, with a median 7-month 1 L DOT and progression-free survival (PFS) of 32.8 months in the early cohort. Both 1 L DOT and PFS were longer with oral compared to injectable regimens. CONCLUSIONS: Although frontline treatment patterns changed significantly, 1 L DOT is short. The uptake of molecular testing and 1 L maintenance is low. These results highlight areas of unmet need in NDMM.

First-line therapy with bendamustine/prednisone/bortezomib-A GMMG trial for non-transplant eligible symptomatic multiple myeloma patients.

OBJECTIVES: The German-speaking Myeloma Multicenter Group (GMMG) conducted this trial to investigate efficacy and safety of the three-drug combination bendamustine/prednisone/bortezomib (BPV) as first-line therapy for elderly patients with multiple myeloma (MM). METHODS: Elderly MM patients requiring first-line therapy and not eligible for intensive treatment were enrolled in this phase IIb multicenter study. Patients were treated with BPV regimen for a maximum of nine cycles. RESULTS: Forty-six patients were included in the trial with a median age of 76 years. Nineteen patients had renal impairment at baseline. The ORR was 78.8% for patients treated with 3 and more BPV cycles and 71.1% for all evaluable patients. The median progression-free survival was 25 months, and overall survival at 24 months was 83.3%. The clinical benefit rate including MR was 91.2%. In patients with renal impairment at baseline, a renal response was observed in 11 pts. with complete recovery of the renal function in six patients. The most frequent CTC grade 3/4 AEs experienced by patients were hematological (17.5%) and infectious (9.8%) complications. No new safety signals were observed for the study drugs under investigation. CONCLUSIONS: Bendamustine/prednisone/bortezomib may serve as a first-line regimen for transplant-ineligible elderly MM patients in particular for patients with renal impairment requiring a fast and durable renal response.

Similar effectiveness of R-CHOP-14 and -21 in diffuse large B-cell lymphoma-data from the prospective German Tumour Registry Lymphatic Neoplasms.

OBJECTIVES: R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) is the standard therapy for patients with previously untreated diffuse large B-cell lymphomas (DLBCL). Dose-dense two-weekly 'R-CHOP-14' was not superior over three-weekly 'R-CHOP-21' in randomised clinical trials (RCTs). We present real-world data on effectiveness of R-CHOP-14 and R-CHOP-21 in patients with DLBCL treated in German routine practice. METHODS: We identified 582 patients with DLBCL treated with R-CHOP-14 or R-CHOP-21 in 92 sites from the prospective clinical cohort study Tumour Registry Lymphatic Neoplasms. Patients' schedules were classified by (a) length of the initial first cycle and (b) length of cycles 1-4. RESULTS: About 55% of patients received R-CHOP-21, 45% R-CHOP-14, in median 6 cycles. 51% and 55% of patients, respectively, were able to continue their initial R-CHOP-14 and R-CHOP-21 schedule. While most characteristics between the patient cohorts were similar, patients receiving R-CHOP-21 presented slightly more often with tumour stage I and lower IPI risk. 3-year overall survival of patients with R-CHOP-14 and R-CHOP-21 did not differ: 84% vs 84% (first cycle), 87% vs 89% (cycles 1-4). CONCLUSIONS: Patients with DLBCL in Germany are slightly more likely to receive R-CHOP-21 than R-CHOP-14. Both schedules are similarly effective in routine practice confirming the results from RCTs.

Survival of non-transplant patients with multiple myeloma in routine care differs from that in clinical trials-data from the prospective German Tumour Registry Lymphatic Neoplasms.

Despite increasing treatment options, multiple myeloma (MM) remains incurable for most patients. Data on improvement of outcomes are derived from selected patient populations enrolled in clinical trials and might not be conferrable to all patients. Therefore, we assessed the trial eligibility, sequential treatment, and survival of non-transplant patients with MM treated in German routine care. The prospective clinical cohort study TLN (Tumour Registry Lymphatic Neoplasms) recruited 285 non-transplant patients with symptomatic MM at start of first-line treatment in 84 centres from 2009 to 2011. Demographic and clinical data were collected until August 2016. Trial-ineligibility was determined by presence of at least one of the common exclusion criteria: heart/renal failure, liver/renal diseases, polyneuropathy, HIV positivity. All other patients were considered potentially trial-eligible. Thirty percent of the patients in our study were classified as trial-ineligible. Median first-line progression-free survival (PFS) and overall survival (OS) of trial-ineligible patients were inferior to that of potentially trial-eligible patients: PFS 16.2 months (95% CI (confidence interval) 11.1-20.4) vs. 27.3 months (95% CI 23.3-33.0); OS 34.2 months (95% CI 21.6-48.1) vs. 58.6 months (95% CI 48.6-64.4). A high percentage of non-transplant patients with MM in German routine care would be ineligible for participation in clinical trials. Despite similar treatment algorithms, their first-line PFS and OS were shorter than those of potentially trial-eligible patients; the survival data of the latter were similar to results from clinical trials. Physicians should be aware of the fact that results from clinical trials may not mirror "real world" patient outcomes when discussing outcome expectations with patients. Trial registration: Clinicaltrials.gov identifier: NCT00889798.

Bendamustine, lenalidomide and dexamethasone (BRd) has high activity as 2nd -line therapy for relapsed and refractory multiple myeloma - a phase II trial.

The combination of lenalidomide (Revlimid® , R) and dexamethasone (d) is a standard regimen for patients with relapsed/refractory multiple myeloma (rrMM). With this regimen, only a small fraction of patients will achieve high quality responses [≥ very good partial response (VGPR)]. The combination of bendamustine (B), lenalidomide and dexamethasone (BRd) has shown high efficacy in patients with advanced rrMM. However, dose-limiting haematotoxicity restricted its use in extensively pre-treated patient populations. This prospective, multicentre Phase II study evaluated the efficacy and safety of BRd in rrMM patients with one prior line of therapy. Fifty patients were enrolled (median age 68·5 years [range 46-83]) and were treated with B 75 mg/m2  days 1, 2; R 25 mg days 1-21 and d (40/20 mg) days 1, 8, 15 and 22, for 6 28-day induction cycles, followed by 12 cycles with Rd alone. Pegfilgrastim was administered according to protocol-defined criteria. The study aimed to demonstrate a complete response (CR)/VGPR rate of >40% after induction therapy. Of 45 evaluable patients, 23 (51%) achieved a CR/VGPR. Grade 4 neutropenia or thrombocytopenia occurred in 17 (34%) and 8 (16%) of patients, respectively. BRd is a safe and efficacious regimen as a second line treatment for rrMM, leading to high quality responses in a considerable proportion of patients.

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.

Bortezomib and low-dose dexamethasone with or without continuous low-dose oral cyclophosphamide for primary refractory or relapsed multiple myeloma: a randomized phase III study.

This phase III, open-label, randomized, controlled study aimed to evaluate the benefit of adding continuous low-dose oral cyclophosphamide to bortezomib-dexamethasone in patients with primary relapsed/refractory multiple myeloma. Patients were randomized 1:1 to receive up to eight 3-week cycles of bortezomib (1.3 mg/m2) and dexamethasone (20 mg; VD; n = 48) or bortezomib-dexamethasone plus oral cyclophosphamide (50 mg; VCD; n = 48). Median time to progression (primary endpoint) was slightly longer in the VD versus VCD group (12.6 vs 9.9 months, P = 0.192), and the hazard ratio for disease progression was in favor of VD (hazard ratio = 0.71, 95% confidence interval = 0.43-1.19, P = 0.196). The overall response rate was 74% with VD and 70% with VCD. Most adverse events were similar in frequency between arms; however, grade ≥ 3 peripheral neuropathy was more frequent in the VCD versus VD arm (15 vs 4%). Infection rate was higher in the VCD arm (64 vs 52%); however, grade ≥3 infection rates were comparable (19 vs 17%). Further trials are needed to determine whether addition of cyclophosphamide to VD at a different dose/schedule confers clinical benefit. This study was terminated prematurely, with insufficient sample size to adequately compare the arms; the results should, therefore, be considered descriptive. This trial is registered: EudraCT Number 2008-003213-27; ClinicalTrials.gov NCT00813150.

Routine treatment of patients with chronic lymphocytic leukaemia by office-based haematologists in Germany-data from the Prospective Tumour Registry Lymphatic Neoplasms.

Various treatment options exist for patients with chronic lymphocytic leukaemia (CLL). Clinical registries provide insight into routine treatment and identify changes in treatment over time. The Tumour Registry Lymphatic Neoplasms prospectively collects data on the treatment of patients with lymphoid B-cell neoplasm as administered by office-based haematologists in Germany. Data on patient and tumour characteristics, co-morbidities, systemic treatments, and outcome parameters are recorded. Eight hundred and six patients with CLL were recruited between May 2009 and August 2013. At the start of first-line treatment, median age was 71 years, 64% were male, and 44% had a Binet stage C disease. The most frequently used first-line/second-line regimens were bendamustine + rituximab (BR, 56%/55%), fludarabine + cyclophosphamide + rituximab (FCR, 22%/11%), and bendamustine (B, 5%/9%). Chlorambucil was used in only 7% (first-line) and 6% (second-line) of patients. Patients treated with FCR were younger and healthier than patients treated with BR. Overall, 91% of first-line treatments were successful (40% complete response). Real-life patient populations differ considerably from patients treated in randomized controlled trials. BR and FCR dominate the first-line and second-line treatments of CLL by office-based haematologists in Germany. Future analysis will investigate progression-free and overall survival times.

Early autologous stem cell transplantation for chronic lymphocytic leukemia: long-term follow-up of the German CLL Study Group CLL3 trial.

The CLL3 trial was designed to study intensive treatment including autologous stem cell transplantation (autoSCT) as part of first-line therapy in patients with chronic lymphocytic leukemia (CLL). Here, we present the long-term outcome of the trial with particular focus on the impact of genomic risk factors, and we provide a retrospective comparison with patients from the fludarabine-cyclophosphamide-rituximab (FCR) arm of the German CLL Study Group (GCLLSG) CLL8 trial. After a median observation time of 8.7 years (0.3-12.3 years), median progression-free survival (PFS), time to retreatment, and overall survival (OS) of 169 evaluable patients, including 38 patients who did not proceed to autoSCT, was 5.7, 7.3, and 11.3 years, respectively. PFS and OS were significantly reduced in the presence of 17p- and of an unfavorable immunoglobulin heavy variable chain mutational status, but not of 11q-. Five-year nonrelapse mortality was 6.5%. When 110 CLL3 patients were compared with 126 matched patients from the FCR arm of the CLL8 trial, 4-year time to retreatment (75% vs 77%) and OS (86% vs 90%) was similar despite a significant benefit for autoSCT in terms of PFS. In summary, early treatment intensification including autoSCT can provide very effective disease control in poor-risk CLL, although its clinical benefit in the FCR era remains uncertain. The trial has been registered with www.clinicaltrials.gov as NCT00275015.

Ambulatory Routine Care in Oncology in Germany: Real-World Survival Data.

INTRODUCTION: Survival data reported by randomised controlled trials are collected in a highly selected patient population and can thus only be transferred to a limited extent to real-world patients: the patients in routine care are mostly older, present with more comorbidities and a worse general state of health. This so-called efficacy-effectiveness gap typically results in inferior survival data in routine healthcare. METHODS: Six prospective clinical tumour registries recruited a total of 11,679 patients receiving systemic therapy in haemato-oncological practices in Germany between 2006 and 2020. For these patients with advanced colorectal cancer, breast cancer, lung cancer, pancreatic cancer, renal cell cancer, and lymphatic neoplasms, overall survival was analysed. A comprehensive literature search was performed to identify suitable pivotal randomised controlled trials. RESULTS: Median overall survival of patients treated in German routine care, with advanced colorectal, breast, lung, and pancreatic cancer, as well as with diffuse large B-cell lymphoma and multiple myeloma, is not shorter than the respective survival data reported in trials. Patients with advanced renal cell carcinoma, chronic lymphocytic leukaemia, or indolent non-Hodgkin lymphoma showed slightly lower survival rates compared to clinical trials. CONCLUSIONS: Despite less favourable patient characteristics, survival data from patients with cancer treated in ambulatory routine care in Germany are in range with results from randomised controlled studies.

Prioritization and Resource Allocation in the Context of the COVID-19 Pandemic: Recommendations for Colorectal and Pancreatic Cancer in Germany.

In the context of the COVID-19 pandemic, there has been a scarcity of resources with various effects on the care of cancer patients. This paper provides an English summary of a German guideline on prioritization and resource allocation for colorectal and pancreatic cancer in the context of the pandemic. Based on a selective literature review as well as empirical and ethical analyses, the research team of the CancerCOVID Consortium drafted recommendations for prioritizing diagnostic and treatment measures for both entities. The final version of the guideline received consent from the executive boards of nine societies of the Association of Scientific Medical Societies in Germany (AWMF), 20 further professional organizations and 22 other experts from various disciplines as well as patient representatives. The guiding principle for the prioritization of decisions is the minimization of harm. Prioritization decisions to fulfill this overall goal should be guided by (1) the urgency relevant to avoid or reduce harm, (2) the likelihood of success of the diagnostic or therapeutic measure advised, and (3) the availability of alternative treatment options. In the event of a relevant risk of harm as a result of prioritization, these decisions should be made by means of a team approach. Gender, age, disability, ethnicity, origin, and other social characteristics, such as social or insurance status, as well as the vehemence of a patient's treatment request and SARS-CoV-2 vaccination status should not be used as prioritization criteria. The guideline provides concrete recommendations for (1) diagnostic procedures, (2) surgical procedures for cancer, and (3) systemic treatment and radiotherapy in patients with colorectal or pancreatic cancer within the context of the German healthcare system.

Bendamustine compared to fludarabine as second-line treatment in chronic lymphocytic leukemia.

Bendamustine demonstrated clinical activity in pre-treated hematological malignancies due to its unique mechanism of action distinct from standard alkylating agents. This study assessed its efficacy in patients with chronic lymphocytic leukemia pre-treated with an alkylator, in comparison to fludarabine. Patients with relapsed chronic lymphocytic leukemia requiring treatment after one previous systemic regimen (usually chlorambucil-based) were randomized to either receive bendamustine 100 mg/m(2) on days 1 and 2 of a 4-week cycle or standard fludarabine treatment consisting of 25 mg/m(2) on days 1 to 5 every 4 weeks. The primary objective was to achieve non-inferior progression-free survival (PFS) with bendamustine. Out of a total of 96 patients randomized, 92 were eligible, 49 allocated to bendamustine and 43 to fludarabine. About half of the patients received six or more cycles. Overall response rates were 76 % on bendamustine and 62 % on fludarabine, with clinical complete response rates of 27 and 9 %, respectively. Median PFS was 20.1 and 14.8 months (hazard ratio, 0.87; 90 % confidence interval, 0.60-1.27), median overall survival 43.8 and 41.0 months (hazard ratio, 0.82). Thrombocytopenia and gastrointestinal toxicities were marginally more frequent on bendamustine, albeit CTC grade 3/4 event incidence was similar. These data suggest at least comparable efficacy of bendamustine vs. fludarabine, pointing to an alternative treatment option in relapsing CLL patients after chlorambucil containing initial chemotherapy.

Real-world clinical effectiveness and safety of CT-P10 in patients with diffuse large B-cell lymphoma: An observational study in Europe.

The rituximab biosimilar CT-P10 is approved for the treatment of non-Hodgkin lymphoma. Previous studies have demonstrated clinical similarity between CT-P10 and reference rituximab. However, real-world data relating to treatment in patients with DLBCL with rituximab biosimilars are limited. This study collected real-world data relating to the effectiveness and safety of CT-P10 treatment from the medical records of 389 patients with DLBCL (24 centers, five European countries). For the primary outcome (clinical effectiveness), overall survival (OS), progression-free survival (PFS), and best response (BR) were assessed. The percentage (95% confidence interval [95% CI]) of patients alive at 12-, 18-, and 30 months postindex (initiation of CT-P10) was 86% (82.4%-89.4%), 81% (76.9%-84.9%), and 76% (71.2%-80.1%), respectively. The PFS rate (percent, [95% CI]) at 12-, 18-, and 30 months postindex was 78% (74.2%-82.5%), 72% (67.9%-76.9%), and 67% (61.9%-71.7%), respectively. Median OS/PFS was not reached. For 82% (n = 312) of patients, the BR to CT-P10 was a complete response. Adverse events were consistent with known effects of chemotherapy. This international, multicenter study provides real-world data on the safety and effectiveness profile of CT-P10 for DLBCL treatment and supports the adoption of CT-P10 for the treatment of DLBCL.

Bendamustine compared with chlorambucil in previously untreated patients with chronic lymphocytic leukaemia: updated results of a randomized phase III trial.

The efficacy of bendamustine versus chlorambucil in a phase III trial of previously untreated patients with Binet stage B/C chronic lymphocytic leukaemia (CLL) was re-evaluated after a median observation time of 54 months in May 2010. Overall survival (OS) was analysed for the first time. At follow-up, investigator-assessed complete response (CR) rate (21·0% vs 10·8%), median progression-free survival (21·2 vs 8·8 months; P < 0·0001; hazard ratio 2·83) and time to next treatment (31·7 vs 10·1 months; P < 0·0001) were improved for bendamustine over chlorambucil. OS was not different between groups for all patients or those ≤65 years, >65 years, responders and non-responders. However, patients with objective response or a CR experienced a significantly longer OS than non-responders or those without a CR. Significantly more patients on chlorambucil progressed to second/further lines of treatment compared with those on bendamustine (78·3% vs 63·6%; P = 0·004). The benefits of bendamustine over chlorambucil were achieved without reducing quality of life. In conclusion, bendamustine is significantly more effective than chlorambucil in previously untreated CLL patients, with the achievement of a CR or objective response appearing to prolong OS. Bendamustine should be considered as a preferred first-line option over chlorambucil for CLL patients ineligible for fludarabine, cyclophosphamide and rituximab.

Results of a Prospective Non-Interventional Post-Authorization Safety Study of Idelalisib in Germany.

BACKGROUND: In pivotal studies, idelalisib demonstrated remarkable efficacy and manageable tolerability in patients with chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL). This prospective, multicenter, non-interventional post-authorization study assessed the characteristics, clinical management, and outcome of CLL and FL patients receiving idelalisib in routine clinical practice in Germany. PATIENTS: Observational study in CLL and FL patients treated with idelalisib between September 2015 and December 2020. RESULTS: A total of 147 patients with CLL and FL were included with a median age of 75 and 71 years, respectively. More than 80% of patients presented with comorbidity and many CLL patients with documented high-risk genetic features, including del(17p)/TP53 mutation or unmutated IGHV. The median progression-free survival (PFS) and overall survival (OS) were not reached in the CLL cohort irrespective of del(17p)/TP53 or unmutated IGHV. The estimated 6-month PFS and OS rates in CLL were 82% and 92%. The estimated 6-month PFS and OS rates for FL were 32.2% and 77.2%. Overall response rates in the CLL and FL cohorts were 70.4% and 36.4%, with the presence of high-risk genetics having no negative impact. No unexpected adverse events were observed. Most frequently reported adverse drug reactions (ADRs) were diarrhea, nausea, pneumonia, rash, and fatigue. CONCLUSION: This real-world study shows that idelalisib is an effective therapy for CLL and FL, regardless of age and high-risk genetic features, consistent with results from previous clinical trials. Collected safety data and the pattern of ADRs reflect those from previous studies.