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AbstractPrognostic assessment in chronic lymphocytic leukemia (CLL) is essential for delivery of timely, personalized therapy. TP53 status, karyotype, IGHV mutational status, minimal residual disease (MRD), gene mutations and markers of cell proliferation were important prognostic tools in the era of chemo-immunotherapy (CIT). With BCL2 inhibitors (BCL2i), outcome is still impacted by IGHV status, TP53 status, complex karyotype, and achievement of undetectable MRD. On the other hand, BTK inhibitors (BTKi) are agnostic to IGHV status, rarely cause MRD negative remissions and are less clearly impacted by TP53 status. Although based on less mature data, outcomes with BCL2i/BTKi combinations are likely influenced by TP53 and IGHV status. Responses to non-covalent BTKI (ncBTKI) are impacted by the mechanism of resistance to previous covalent BTKi. Finally, responses to chimeric antigen receptor T cell therapy (CAR-T) appear independent of TP53 status, but dependent on overall T- cell fitness. [ABSTRACT FROM AUTHOR]

This real-world retrospective cohort study using Australian Pharmaceutical Benefits Scheme (PBS) 10% investigated changes in chronic lymphocytic leukemia (CLL) treatment by line of therapy, time-to-next-treatment, treatment duration, and overall survival (OS). Overall, 803 patients received their first PBS-reimbursed CLL medication between 1 January 2011 to 31 July 2021 (median age: 70 years; 64.6% male), 289 post-1 August 2020. In 2011, most first-line (1 L) prescribing was fludarabine, cyclophosphamide, and rituximab (FCR). By 2021, common 1L were chlorambucil ± CD20 (26.1%), Bruton Tyrosine Kinase inhibitor (BTKi) (26.1%), and CD20 monotherapy (23.9%). In 2011, relapsed/refractory (R/R) CLL treatment was CD20 monotherapy or FCR. By 2021, BTKi (57.7%) and venetoclax ± CD20 (26.1%) were most common. Compared to FCR, 1 L treatment duration (Hazard Ratio) was shorter for CD20 monotherapy (1.7) or chlorambucil ± CD20 (2.5). In R/R CLL, median duration was 24 (ibrutinib) and 19 months (venetoclax). Median OS was 127 months. CLLtreatment pattern shave greatly changed in Australia since the introduction of novel therapies. [ABSTRACT FROM AUTHOR]

The article discusses the impact of dose reductions and interruptions in patients receiving ibrutinib treatment for Chronic Lymphocytic Leukemia (CLL). While some studies suggest that reduced doses may compromise efficacy, real-world observational data presented by Shadman and colleagues indicate that dose reductions do not necessarily affect disease control and may even lead to longer treatment duration. However, conflicting findings from Barr and colleagues show that reduced dose intensity could be associated with reduced therapeutic effect. Additional studies by Williams and the United Kingdom CLL Forum provide further insights into the effects of dose reductions and interruptions on patient outcomes, highlighting the complexity of interpreting such data in clinical settings. [Extracted from the article]

Ibrutinib is a small molecule inhibitor of Bruton's tyrosine kinase indicated for the treatment of relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and mantle cell lymphoma (MCL). The Named Patient Program in Australia and New Zealand (ANZ NPP) provided access to ibrutinib treatment to 1126 R/R CLL/SLL and 330 R/R MCL patients, prior to Pharmaceutical Benefits Scheme listing. This study aimed to assess the duration of treatment for the ANZ NPP patients, as an indicator of efficacy and tolerability of ibrutinib in the real world. Based on the NPP data, ibrutinib provided a median of 47 months clinical benefit for participants with CLL/SLL and 14 months clinical benefit for those with MCL; outcomes that are consistent with the clinical trial results and further support the well-established efficacy and safety profile of ibrutinib in the real world. [ABSTRACT FROM AUTHOR]

The low grade chronic lymphoproliferative disorders include chronic lymphocytic leukemia, Waldenstroms macroglobulinemia, follicular lymphoma and hairy cell leukemia. Traditionally considered incurable, these disorders have been associated with a risk of haematological and solid organ malignancies secondary to both the underlying disease and the associated treatment. The introduction of purine analogues into treatment paradigms has seen increased rates of therapy related myelodysplasia reported and it remains unclear yet on the impact the targeted novel therapies play in the development of secondary cancers. We review the rates of secondary malignancy in the chronic lymphoproliferative disorders with a particular focus on the role of the purine analogues in the development of therapy related MDS. [ABSTRACT FROM AUTHOR]

Primary CNS lymphoma (PCNSL) in immunocompetent patients is a disease of older adults who are often unsuitable for the high dose therapy or experience substantial morbidity from whole brain radiotherapy. As therapeutic studies in older patients are limited, there is a need for real world data to guide patient care. Here we report a series of 38 consecutive immunocompetent patients with PCNSL treated with curative intent using R-MPV/Ara-C with omission of consolidative radiotherapy in older patients. Outcomes for patients aged < 60 years and > 60 years were similar with overall response rates of 100% vs 85%, (p =.30), 4-year PFS of 81% vs 82% (p =.92) and 4-year OS of 80% vs 77% (p =.52) respectively. This study supports the premise that older patients with PCNSL can be effectively treated with sequential and response-adapted methotrexate (MTX) dosing without the need for WBRT or autologous stem cell transplantation (ASCT). [ABSTRACT FROM AUTHOR]

We describe a patient with co-existing metastatic melanoma and indolent chronic lymphocytic leukemia (CLL) developing autoimmune hemolytic anemia after a single dose of ipilimumab. Our patient's autoimmune hemolytic anemia was refractory to standard therapies including corticosteroids, IVIg and cyclophosphamide. With respect to the patient's melanoma, his upper back dermal melanoma deposits continued to progress requiring intradermal PV-10 (Rose Bengal) therapy. [Extracted from the article]

The development of bruton tyrosine kinase inhibitors (BTKi) has been a significant advancement in the treatment of chronic lymphocytic leukemia and related B-cell malignancies. As experience in using ibrutinib increased, the first drug to be licensed in its class, atrial fibrillation (AF) emerged as an important side effect. The intersection between BTKi therapy for B-cell malignancies and AF represents a complex area of management with scant evidence for guidance. Consideration needs to be taken regarding the interplay of increased bleeding risk versus thromboembolic complications of AF, drug interactions between ibrutinib and anticoagulants and antiarrhythmic agents, and the potential for other, as yet seldom reported cardiac side effects. This review describes the current knowledge regarding BTKi and potential pathophysiologic mechanisms of AF and discusses the management of BTKi-associated AF. Finally, a review of the second generation BTKi is provided and gaps in knowledge in this evolving field are highlighted. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 61-year-old man with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who was presented with right supraclavicular lymphadenopathy. The patient was given ibrutinib because of his severe thrombocytopenia. He eventually developed central nervous system immune reconstitution inflammatory syndrome after receiving the drug.

Despite its efficacy in prospective trials, full dose fludarabine, cyclophosphamide and rituximab (FCR) may be too toxic for elderly patients with chronic lymphocytic leukemia (CLL) in clinical practice. We retrospectively reviewed the impact of dose reductions in FCR therapy on the outcomes of 42 consecutive patients aged 65–87 (median 72) years. Despite a median cumulative fludarabine dose reduction of 50% from full dose, the objective response and complete response rates were 86% and 38% respectively (frontline 94%/59%; previously treated 80%/24%). Dose reductions of 25–75% were not significantly associated with inferior progression free survival compared to minimal reductions (≤25%) (p = 0.49), and did not preclude deep responses, including six cases (14%) of minimal residual disease negativity. Although hematological and infectious toxicities were common, treatment limiting adverse effects were infrequent. Dose attenuated FCR appears to have preserved efficacy and may be a viable therapeutic option for elderly patients with CLL. [ABSTRACT FROM PUBLISHER]