First-Line Venetoclax Combinations in Chronic Lymphocytic Leukemia.

BACKGROUND: Randomized trials of venetoclax plus anti-CD20 antibodies as first-line treatment in fit patients (i.e., those with a low burden of coexisting conditions) with advanced chronic lymphocytic leukemia (CLL) have been lacking. METHODS: In a phase 3, open-label trial, we randomly assigned, in a 1:1:1:1 ratio, fit patients with CLL who did not have TP53 aberrations to receive six cycles of chemoimmunotherapy (fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab) or 12 cycles of venetoclax-rituximab, venetoclax-obinutuzumab, or venetoclax-obinutuzumab-ibrutinib. Ibrutinib was discontinued after two consecutive measurements of undetectable minimal residual disease or could be extended. The primary end points were undetectable minimal residual disease (sensitivity, <10-4 [i.e., <1 CLL cell in 10,000 leukocytes]) as assessed by flow cytometry in peripheral blood at month 15 and progression-free survival. RESULTS: A total of 926 patients were assigned to one of the four treatment regimens (229 to chemoimmunotherapy, 237 to venetoclax-rituximab, 229 to venetoclax-obinutuzumab, and 231 to venetoclax-obinutuzumab-ibrutinib). At month 15, the percentage of patients with undetectable minimal residual disease was significantly higher in the venetoclax-obinutuzumab group (86.5%; 97.5% confidence interval [CI], 80.6 to 91.1) and the venetoclax-obinutuzumab-ibrutinib group (92.2%; 97.5% CI, 87.3 to 95.7) than in the chemoimmunotherapy group (52.0%; 97.5% CI, 44.4 to 59.5; P<0.001 for both comparisons), but it was not significantly higher in the venetoclax-rituximab group (57.0%; 97.5% CI, 49.5 to 64.2; P = 0.32). Three-year progression-free survival was 90.5% in the venetoclax-obinutuzumab-ibrutinib group and 75.5% in the chemoimmunotherapy group (hazard ratio for disease progression or death, 0.32; 97.5% CI, 0.19 to 0.54; P<0.001). Progression-free survival at 3 years was also higher with venetoclax-obinutuzumab (87.7%; hazard ratio for disease progression or death, 0.42; 97.5% CI, 0.26 to 0.68; P<0.001), but not with venetoclax-rituximab (80.8%; hazard ratio, 0.79; 97.5% CI, 0.53 to 1.18; P = 0.18). Grade 3 and grade 4 infections were more common with chemoimmunotherapy (18.5%) and venetoclax-obinutuzumab-ibrutinib (21.2%) than with venetoclax-rituximab (10.5%) or venetoclax-obinutuzumab (13.2%). CONCLUSIONS: Venetoclax-obinutuzumab with or without ibrutinib was superior to chemoimmunotherapy as first-line treatment in fit patients with CLL. (Funded by AbbVie and others; GAIA-CLL13 ClinicalTrials.gov number, NCT02950051; EudraCT number, 2015-004936-36.).

The effect of a palliative care pathway on medical interventions at the end of life: a pre-post-implementation study.

PURPOSE: Adequate integration of palliative care in oncological care can improve the quality of life in patients with advanced cancer. Whether such integration affects the use of diagnostic procedures and medical interventions has not been studied extensively. We investigated the effect of the implementation of a standardized palliative care pathway in a hospital on the use of diagnostic procedures, anticancer treatment, and other medical interventions in patients with incurable cancer at the end of their life. METHODS: In a pre- and post-intervention study, data were collected concerning adult patients with cancer who died between February 2014 and February 2015 (pre-PCP period) or between November 2015 and November 2016 (post-PCP period). We collected information on diagnostic procedures, anticancer treatments, and other medical interventions during the last 3 months of life. RESULTS: We included 424 patients in the pre-PCP period and 426 in the post-PCP period. No differences in percentage of laboratory tests (85% vs 85%, p = 0.795) and radiological procedures (85% vs 82%, p = 0.246) were found between both groups. The percentage of patients who received anticancer treatment or other medical interventions was lower in the post-PCP period (40% vs 22%, p < 0.001; and 42% vs 29%, p < 0.001, respectively). CONCLUSIONS: Implementation of a PCP resulted in fewer medical interventions, including anticancer treatments, in the last 3 months of life. Implementation of the PCP may have created awareness among physicians of patients' impending death, thereby supporting caregivers and patients to make appropriate decisions about medical treatment at the end of life. TRIAL REGISTRATION NUMBER: Netherlands Trial Register; clinical trial number: NL 4400 (NTR4597); date registrated: 2014-04-27.

Hospitalisations of patients with cancer in the last stage of life. Reason to improve advance care planning?

OBJECTIVE: The aim of this study is to examine why patients are hospitalised in the last stage of life. METHODS: Our study was conducted in a large Dutch teaching hospital. We conducted a retrospective chart review of patients aged ≥18 years who died of cancer either during hospitalisation or after discharge to receive terminal care outside the hospital. We collected data about the characteristics of these hospitalisations and indicators of advance care planning. RESULTS: Of the 264 deceased patients, 56% had died in the hospital and 44% after hospital discharge. Of all patients, 80% had been admitted to the hospital because of symptom distress. Dyspnoea (39%) and pain (33%) were the most common symptoms. Most patients underwent diagnostic procedures (laboratory tests [97%] and radiology tests [91%]) and received medical treatment (analgesics [71%] and antibiotics [55%]) during their hospitalisation. A 'Do-Not-Resuscitate' code had been recorded before admission in 42% of the patients and in an additional 52% during admission. CONCLUSION: Our study shows that patients with cancer in the last stage of life were mainly admitted to the hospital because of symptom distress. Some hospitalisations and in-hospitals deaths may be avoided by more timely recognition of patients' impending death and start of advance care planning.

Quality of hospital discharge letters for patients at the end of life: A retrospective medical record review.

OBJECTIVE: For patients who are discharged to go home after a hospitalisation, timely and adequately informing their general practitioner is important for continuity of care, especially at the end of life. We studied the quality of the hospital discharge letter for patients who were hospitalised in their last year of life. METHODS: A retrospective medical record review was performed. Included patients had been admitted to the hospital during the period 1 January to 1 July 2017 and had died within a year after discharge. RESULTS: Data were collected from records of 108 patients with cancer or other diseases. For 57 patients (53%), the discharge letter included information that related to their limited life expectancy (e.g., agreements about treatment limitations), whereas the patient's limited life expectancy was addressed in the medical record in 76 cases (70%). We found related information in discharge letters for 36 patients (66%) who died <3 months compared to 21 patients (40%) who died 3-12 months after hospitalisation (p < 0.01). CONCLUSION: For patients with a limited life expectancy going home after a hospitalisation, one out of two hospital discharge letters lacked any information addressing their limited life expectancy. Specific guidelines for medical information exchange between care settings are needed.

Effects of Implementation of a Standardized Palliative Care Pathway for Patients with Advanced Cancer in a Hospital: A Prospective Pre- and Postintervention Study.

CONTEXT: Early integration of oncology and palliative care has been recommended to improve patient outcomes at the end of life. A standardized Palliative Care Pathway, consisting of a structured electronic medical checklist, may support such integration. OBJECTIVES: We studied the effect of implementation of a Palliative Care Pathway on patients' place of death and advance care planning. METHODS: We conducted a prospective pre- and postimplementation study of adult patients with cancer from a single hospital who died between February 2014 and February 2015 (pre-implementation period) or between November 2015 and November 2016 (post-implementation period). RESULTS: We included 424 patients in the pre- and 426 in the post-implementation period. The pathway was started for 236 patients (55%) in the post-implementation period, on average 33 days (IQR 12-73 days) before death. 74% and 77% of the patients died outside hospital in the pre- and post-implementation period, respectively (P = 0.360). When the PCP was initiated, 83% died outside hospital. Bad-news conversations (75% and 62%, P < 0.001) and preferred place of death (47% and 32%, P < 0.001) were more often documented in the pre-implementation period, whereas a DNR-code was more often documented during the post-implementation period (79% and 89%, P < 0.001). CONCLUSIONS: Implementation of a Palliative Care Pathway had no overall positive effect on place of death and several aspects of advance care planning. Start of a Palliative Care Pathway in the last months of life may be too late to improve end-of-life care. Future research should focus on strategies enabling earlier start of palliative care interventions.