Outcomes in Patients with High-Risk Features after Fixed-Duration Ibrutinib plus Venetoclax: Phase II CAPTIVATE Study in First-Line Chronic Lymphocytic Leukemia.

PURPOSE: The CAPTIVATE study investigated first-line ibrutinib plus venetoclax for chronic lymphocytic leukemia in 2 cohorts: minimal residual disease (MRD)-guided randomized discontinuation (MRD cohort) and Fixed Duration (FD cohort). We report outcomes of fixed-duration ibrutinib plus venetoclax in patients with high-risk genomic features [del(17p), TP53 mutation, and/or unmutated immunoglobulin heavy chain (IGHV)] in CAPTIVATE. PATIENTS AND METHODS: Patients received three cycles of ibrutinib 420 mg/day then 12 cycles of ibrutinib plus venetoclax (5-week ramp-up to 400 mg/day). FD cohort patients (n = 159) received no further treatment. Forty-three MRD cohort patients with confirmed undetectable MRD (uMRD) after 12 cycles of ibrutinib plus venetoclax received randomized placebo treatment. RESULTS: Of 195 patients with known status of genomic risk features at baseline, 129 (66%) had ≥1 high-risk feature. Overall response rates were >95% regardless of high-risk features. In patients with and without high-risk features, respectively, complete response (CR) rates were 61% and 53%; best uMRD rates: 88% and 70% (peripheral blood) and 72% and 61% (bone marrow); 36-month progression-free survival (PFS) rates: 88% and 92%. In subsets with del(17p)/TP53 mutation (n = 29) and unmutated IGHV without del(17p)/TP53 mutation (n = 100), respectively, CR rates were 52% and 64%; uMRD rates: 83% and 90% (peripheral blood) and 45% and 80% (bone marrow); 36-month PFS rates: 81% and 90%. Thirty-six-month overall survival (OS) rates were >95% regardless of high-risk features. CONCLUSIONS: Deep, durable responses and sustained PFS seen with fixed-duration ibrutinib plus venetoclax are maintained in patients with high-risk genomic features, with similar PFS and OS to those without high-risk features. See related commentary by Rogers, p. 2561.

Retrospective Analysis of the Efficacy and Tolerability of Gemcitabine-Based Chemotherapy in Relapsed/Refractory Lymphoma Patients Not Eligible for Stem Cell Transplant.

INTRODUCTION: Gemcitabine-based regimens are effective salvage therapy for RR lymphoma patients eligible for ASCT, but there is limited data in transplant-ineligible (TIE) patients. Here, we present a retrospective analysis on the outcome of TIE adult patients with RR lymphoma treated with gemcitabine, cisplatin or carboplatin and dexamethasone (GDP/GDCarboP) +/- rituximab regimen in our center. PATIENTS: We identified 33 patients: 54.5% diffuse large Bcell lymphoma (DLBCL), 6.1% double/triple hit lymphoma, 15% follicular lymphoma, 18% T-cell lymphoma, and 6% classical Hodgkin lymphoma. Majority of the patients had advanced-stage disease and raised LDH at relapse. The cohort's median age was 71 years. The median number of prior lines of treatment was 2, and 60.6% were refractory to their last line of treatment. RESULTS: The overall response rate was 33% (complete response 15%) for the entire cohort and 62.5% for DLBCL patients not refractory to prior line of treatment. At median follow-up of 25 months, the median duration of response and overall survival in the responders were not reached. Conversely, the median overall survival for the non-responders was dismal at 5 months. Fifty-five percent required treatment alteration (dose attenuation or omission and treatment delay for >1 week) due to adverse events, 73% needed transfusion, and 70% had at least 1 hospital admission during treatment. CONCLUSION: Our real-world data showed that GDP/GDCarboP provides meaningful efficacy and durability, especially among the responders. However, dose modification and inpatient support are frequently needed, indicating the need for good supportive care and close follow-up in this frailer population.

Electronic FRAIL score as a predictor of treatment outcomes in older patients with diffuse large B-cell lymphoma.

INTRODUCTION: Frailty is a significant risk factor for poor outcomes among older patients with diffuse large B-cell lymphoma (DLBCL). We present an automatically derived electronic frailty screening tool (FRAIL score) as a predictor of patient outcomes. METHODS: Patients aged 70 or over who received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy for DLBCL between 2010 and ` were retrospectively assessed for their FRAIL scores. Measured treatment outcomes included overall survival (OS), progression-free survival (PFS), and treatment-limiting toxicity from chemotherapy. RESULTS: A total of 96 patients were analysed. When stratified by FRAIL score, the estimated 5-year PFS was 58%, 48% and, 0% for those with scores of 0-1, 2, and 3-5, respectively (p = 0.012). Similarly, the estimated 5-year OS for these respective groups was 60%, 60% and 0% (p = 0.010). Patients with a FRAIL score of 3-5 were also more likely than those with a score of 0-1 to need dose reduction or treatment delay due to toxicity (odds ratio [OR] 12.5, 95% confidence interval [CI] 10.42-109.72) and less likely to complete the six planned cycles of treatment (OR 0.14, 95% CI 0.03-0.77). CONCLUSION: The FRAIL score is independently predictive of OS, PFS, and treatment-related toxicity in older patients with DLBCL receiving R-CHOP chemotherapy. Once implemented, it provides a quick and accessible method to stratify disease and treatment-related risk among these patients.

Central line-associated bloodstream infections in adult hematology patients with febrile neutropenia: an evaluation of surveillance definitions using differential time to blood culture positivity.

We used differential time to positivity between central and peripheral blood cultures to evaluate the positive predictive value (PPV) of the National Healthcare Safety Network central line-associated bloodstream infection (CLABSI) surveillance definition among hematology patients with febrile neutropenia. The PPV was 27.7%, which suggests that, when the definition is applied to this population, CLABSI rates will be substantially overestimated.