End Point Surrogacy in First-Line Chronic Lymphocytic Leukemia.

Purpose: Surrogate end points are commonly used to estimate treatment efficacy in clinical studies of chronic lymphocytic leukemia (CLL). This patient- and trial-level analysis describes the correlation between progression-free survival (PFS) and minimal residual disease (MRD) with overall survival (OS) in first-line trials for CLL.

Patients And Methods: First, patient-level correlation was confirmed using source data from 12 frontline German CLL Study Group (GCLLSG)-trials.

[Frailty in Oncology: Updated Recommendations for Clinical Practice].

Frailty is a clinical condition associated with aging and resulting in increased risk of adverse outcomes upon exogenous or endogenous stressors. In oncology, cancer treatment itself can be a stressor event. In older cancer patients, frailty therefore not only enhances the probability of age-related health events such as institutionalization or falls, but also of treatment complications such as toxicity and interruption or discontinuation of therapy.

Reassessing the chronic lymphocytic leukemia International Prognostic Index in the era of targeted therapies.

We evaluated the chronic lymphocytic leukemia International Prognostic Index (CLL-IPI) in patients with CLL treated first line with targeted drugs (n = 991) or chemoimmunotherapy (n = 1256). With a median observation time of 40.5 months, the 3-year progression-free survival (PFS) rates for targeted drug-treated patients varied by CLL-IPI risk group: 96.

Frailty and Cancer: Current Perspectives on Assessment and Monitoring.

Frailty, an age-related condition of increased vulnerability to acute endogenous or exogenous stressors, is a key barrier to successful treatment of cancer in older people. In this group of patients, assessment of frailty is required before starting a new treatment. According to guidelines, the gold standard to assess frailty in older adults with cancer is geriatric screening followed by geriatric assessment (GA) across essential GA-domains (social status, physical function, nutrition, cognition, emotion, co-morbidity, polypharmacy).

Frailty assessment in the care of older people with haematological malignancies.

Frailty, defined as an age-related state of increased vulnerability to acute stressors, is a major challenge in the care of older people with haematological malignancies. Growing evidence from multiple studies suggests that a systematic evaluation of frailty in these patients by use of appropriate assessment tools might help clinicians to make appropriate treatment decisions and initiate frailty interventions. Here, we summarise current knowledge on the origin, decision relevance, assessment methods, and possible treatments of frailty in older people with haematological malignancies.

Detecting measurable residual disease beyond 10-4 by an IGHV leader-based NGS approach improves prognostic stratification in CLL.

The sensitivity of conventional techniques for reliable quantification of minimal/measurable residual disease (MRD) in chronic lymphocytic leukemia (CLL) is limited to MRD 10-4. Measuring MRD <10-4 could help to further distinguish between patients with CLL with durable remission and those at risk of early relapse. We herein present an academically developed immunoglobulin heavy-chain variable (IGHV) leader-based next-generation sequencing (NGS) assay for the quantification of MRD in CLL.

A comprehensive approach to therapy of haematological malignancies in older patients.

Haematological malignancies are a heterogeneous group of diseases with diverse incidence. In Europe, the median age at diagnosis across all disease entities is 69 years. Incidence generally increases with age, reaching a maximum at 75-99 years, with the notable exceptions of Hodgkin lymphoma and acute lymphocytic leukaemia.

[Malignant Diseases in the Elderly].

A majority of patients with newly diagnosed malignant disease are 70 years old or older. Frailty - i. e.

Prognostic impact of prevalent chronic lymphocytic leukemia stereotyped subsets: analysis within prospective clinical trials of the German CLL Study Group (GCLLSG).

Almost one-third of all patients with chronic lymphocytic leukemia (CLL) express stereotyped B cell receptor immunoglobulins (BcR IG) and can be assigned to distinct subsets, each with a particular BcR IG. The largest stereotyped subsets are #1, #2, #4 and #8, associated with specific clinicobiological characteristics and outcomes in retrospective studies. We assessed the associations and prognostic value of these BcR IG in prospective multicenter clinical trials reflective of two different clinical situations: i) early-stage patients (watch-and-wait arm of the CLL1 trial) (n=592); ii) patients in need of treatment, enrolled in 3 phase III trials (CLL8, CLL10, CLL11), treated with different chemo-immunotherapies (n=1861).

[Multiple myeloma in old people : Practical skills for geriatricians and general practitioners].

Multiple myeloma is an age-associated disease. In aged and multimorbid patients the diagnosis could be delayed due to the diversity of symptoms of this disease. Key diagnostic steps are the detection of an M protein as a surrogate of clonal plasma cell proliferation and evaluation of the CRAB criteria (hypercalcemia, renal insufficiency, anemia, bone lesions).

Genomic alterations in high-risk chronic lymphocytic leukemia frequently affect cell cycle key regulators and NOTCH1-regulated transcription.

To identify genomic alterations contributing to the pathogenesis of high-risk chronic lymphocytic leukemia (CLL) beyond the well-established role of aberrations, we comprehensively analyzed 75 relapsed/refractory and 71 treatment-naïve high-risk cases from prospective clinical trials by single nucleotide polymorphism arrays and targeted next-generation sequencing. Increased genomic complexity was a hallmark of relapsed/refractory and treatment-naïve high-risk CLL. In relapsed/refractory cases previously exposed to the selective pressure of chemo(immuno)therapy, gain(8)(q24.

Mode of progression after first line treatment correlates with outcome of chronic lymphocytic leukemia (CLL).

In CLL, progressive disease (PD) following remission after first line treatment can present with varying phenotypes. We hypothesized that the mode of PD correlates with clinical outcomes. Data from three phase III trials of the German CLL Study Group (GCLLSG) (CLL8, CLL10, CLL11) including a total of 2159 patients receiving first line (immuno)-chemotherapy (FCR, FC, CLB, CLB-R, CLB-Ob) were analyzed.

Venetoclax and Obinutuzumab in Patients with CLL and Coexisting Conditions.

Background: The BCL2 inhibitor venetoclax has shown activity in patients with chronic lymphocytic leukemia (CLL), but its efficacy in combination with other agents in patients with CLL and coexisting conditions is not known.

Methods: In this open-label, phase 3 trial, we investigated fixed-duration treatment with venetoclax and obinutuzumab in patients with previously untreated CLL and coexisting conditions. Patients with a score of greater than 6 on the Cumulative Illness Rating Scale (scores range from 0 to 56, with higher scores indicating more impaired function of organ systems) or a calculated creatinine clearance of less than 70 ml per minute were randomly assigned to receive venetoclax-obinutuzumab or chlorambucil-obinutuzumab.

Prognostic Impact of Natural Killer Cell Count in Follicular Lymphoma and Diffuse Large B-cell Lymphoma Patients Treated with Immunochemotherapy.

Purpose: Natural killer (NK) cells are key effector cells for anti-CD20 monoclonal antibodies (mAb), such as obinutuzumab and rituximab. We assessed whether low pretreatment NK-cell count (NKCC) in peripheral blood or tumor tissue was associated with worse outcome in patients receiving antibody-based therapy.

Patients And Methods: Baseline peripheral blood NKCC was assessed by flow cytometry (CD3CD56 and/or CD16 cells) in 1,064 of 1,202 patients with follicular lymphoma treated with obinutuzumab or rituximab plus chemotherapy in the phase III GALLIUM trial (NCT01332968) and 1,287 of 1,418 patients with diffuse large B-cell lymphoma (DLBCL) treated with obinutuzumab or rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (G-CHOP or R-CHOP) in the phase III GOYA trial (NCT01287741).

Management of unfit elderly patients with chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is a disease characterized by an increasing incidence with age reaching 35/100,000 in patients over 85 years. Elderly CLL patients carry several challenges, which have to be considered particularly in advanced stages including a higher risk of infections and individual differences in comorbidities and geriatric syndromes. Although no specific tool for geriatric evaluation in CLL has been developed so far, several of them (e.

Outcome of patients aged 80 years or older treated for chronic lymphocytic leukaemia.

Clinical management of chronic lymphocytic leukaemia (CLL) in patients aged ≥80 years is based on limited evidence due to the lack of published information. Therefore, we analysed CLL patients aged ≥80 years using data from seven phase III clinical trials of the German CLL Study Group. Among 3552 participants, 152 were ≥80 years old at initiation of first-line study treatment.

Prognostic value of MRD in CLL patients with comorbidities receiving chlorambucil plus obinutuzumab or rituximab.

There is a Commentary on this article in this issue.

Multidisciplinary care in the hematology clinic: Implementation of geriatric oncology.

Multidisciplinary care is believed to provide benefits to patients with cancer. Tumor board conferences as well aspalliative care or psycho-oncological services have not only become common in oncology, but also in hematology clinics dedicated to the treatment of hematological cancers. Malignant hematological diseases are highly prevalent among older persons.

[Which drugs in Hemato-Oncology are Unnecessary or Inappropriate for Use in the Elderly?].

There is a vast amount of drugs and therapeutic regimens available today to treat hemato-oncological diseases. This offers new opportunities to close known gaps of undertreatment in older individuals with cancer, but also increases the risk of overtreatment in this patient group. Currently available criteria (drug listings) for potentially inadequate prescribing in the elderly are not matured enough to serve hemato-oncologists as a guidance when trying to identify unnecessary or inappropriate cancer medication in routine clinical practice.