The efficacy and safety of venetoclax therapy in elderly patients with relapsed, refractory chronic lymphocytic leukaemia.

Elderly chronic lymphocytic leukaemia (CLL) patients treated outside of trials have notably greater toxicity with the Bruton's tyrosine kinase inhibitor ibrutinib compared to younger patients. It is not known whether the same holds true for the B-cell lymphoma 2 inhibitor venetoclax. We provide a comprehensive analysis of key safety measures and efficacy in 342 patients comparing age categories ≥75 and <75 years treated in the relapsed, refractory non-trial setting. We demonstrate that venetoclax has equivalent efficacy and safety in relapsed/refractory CLL patients who are elderly, the majority of whom are previous ibrutinib-exposed and therefore may otherwise have few clear therapeutic options.

Understanding treatment decisions for Hodgkin lymphoma: a qualitative study.

Hodgkin lymphoma (HL) affects older and younger patients and includes multiple options for initial treatment. We sought to examine the decision processes of practicing oncologists caring for patients with newly diagnosed HL. Through semi-structured interviews, we explored their perspectives about treatment decisions. We completed thematic analysis using the Anderson Behavioral Model of Health Services framework to identify factors associated with initial decisions. We completed 22 interviews, grouping findings into contextual factors, individual characteristics, and physician preferences. Paternalism was widely cited, along with collaboration between community and academic colleagues. Participants used sequential therapy but not geriatric assessment in care for older patients. Physicians had varied responses about use of frontline brentuximab vedotin (Bv)-based therapy based on perceptions about benefit versus toxicity. Our work suggests a need to further understand the heterogeneity of clinical practices, especially in the post-approval setting of new therapies.

Chloroma of the Bladder: A Case Report of Leukemia Progression Presenting as Hematuria.

Myeloid sarcoma (MS) is a rare extramedullary manifestation of acute myelogenous leukemia (AML). The mass is composed of primitive myeloid cells that can occur in a variety of organs, most commonly the skin, lymph nodes, GI tract, bone, breast, and CNS. Involvement of the genitourinary tract is rare. Consensus on treatment of MS has not been established, but management typically involves systemic therapy, such as chemotherapy or allogeneic hematopoietic stem cell transplant as well as palliative local therapies such as radiation or surgery. Outcomes of MS using novel AML therapies, such as BCL-2 inhibitors or IDH inhibitors, remain undescribed. We describe a rare case of a 70-year-old man presenting with MS of the urinary bladder complicating known secondary AML (RUNX1 and IDH2 mutated). Prior to development of bladder MS, the patient had received decitabine, enasidenib, and venetoclax. Following diagnosis, he was treated with cytarabine and venetoclax. To our knowledge, this is the first case of bladder MS treated with a BCL-2 inhibitor.

Tumor Lysis, Adverse Events, and Dose Adjustments in 297 Venetoclax-Treated CLL Patients in Routine Clinical Practice.

PURPOSE: Clinical trials of venetoclax reported negligible rates of clinical tumor lysis syndrome (TLS) in patients with chronic lymphocytic leukemia (CLL) when using an extended dose escalation schedule. We aimed to understand TLS prophylaxis, rates of select adverse events (AE), and impact of dosing modifications in routine clinical practice. EXPERIMENTAL DESIGN: This retrospective cohort study included 297 CLL venetoclax-treated patients outside of clinical trials in academic and community centers. Demographics, baseline disease characteristics, venetoclax dosing, TLS risk and prophylaxis, and AEs were collected. RESULTS: The group was 69% male, 96% had relapsed/refractory CLL, 45% had deletion chromosome 17p, 84% had unmutated IGHV, 80% received venetoclax monotherapy, and median age was 67. TLS risk was categorized as low (40%), intermediate (32%), or high (28%), and 62% had imaging prior to venetoclax initiation. Clinical TLS occurred in 2.7% of patients and laboratory TLS occurred in 5.7%. Pre-venetoclax TLS risk group and creatinine clearance independently predict TLS development in multivariable analysis. Grade 3/4 AEs included neutropenia (39.6%), thrombocytopenia (29.2%), infection (25%), neutropenic fever (7.9%), and diarrhea (6.9%). Twenty-two patients (7.4%) discontinued venetoclax due to an AE. Progression-free survival was similar regardless of number of dose interruptions, length of dose interruption, and stable venetoclax dose. CONCLUSIONS: These data provide insights into current use of venetoclax in clinical practice, including TLS rates observed in clinical practice. We identified opportunities for improved adherence to TLS risk stratification and prophylaxis, which may improve safety.