Q3 2022: Additional information and data in acute leukemia
Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN (full article: https://doi.org/10.1182/blood.2022016867)
The 2010 and 2017 editions of the European LeukemiaNet (ELN) recommendations for diagnosis and management of AML in adults are widely recognized among physicians and investigators. There have been major advances in our understanding of AML, including new knowledge about the molecular pathogenesis of AML, leading to an update of the disease classification, technological progress in genomic diagnostics and assessment of measurable residual disease, and the successful development of new therapeutic agents, such as FLT3, IDH1, IDH2, and BCL2 inhibitors. These advances have prompted this update that includes a revised ELN genetic risk classification, revised response criteria, and treatment recommendations.
The combination of the IDH1 inhibitor ivosidenib and azacitidine demonstrated significant clinical benefit in patients with newly diagnosed IDH1-mutated AML, according to phase III results published in The New England Journal of Medicine. With a median follow-up of just more than one year, the median event-free survival (EFS) was significantly longer for patients treated with ivosidenib plus azacitidine compared with those treated with azacitidine plus placebo (hazard ratio for treatment failure, relapse from remission, or death = 0.33; 95% CI 0.16-0.69; p=0.002). (Ref. Montesinos P, Recher C, Vives S, et al. Ivosidenib and azacitidine in IDH1-mutated acute myeloid leukemia. N Engl J Med. 2022;386:1519-1531.)
Combination treatment with the tyrosine kinase inhibitor nilotinib and anti–PD-L1 dramatically improves long-term survival of leukemic mice. Depletion of CD4+ T cells prior to therapy completely abrogates the survival benefit, implicating CD4+ T cells as key drivers of the protective anti-leukemia immune response. Indeed, treatment with anti–PD-L1 leads to clonal expansion of leukemia-specific CD4+ T cells with the aforementioned helper/cytotoxic phenotype as well as reduced expression of exhaustion markers. These findings support efforts to use PD1/PD-L1 checkpoint blockade in clinical trials and highlight the importance of CD4+ T-cell dysfunction in limiting the endogenous anti-leukemia response. (Ref: https://doi.org/10.1182/blood.2021015341)
Outcomes for allogeneic hematopoietic cell transplantation (alloHCT) for ALL have improved in the past 30 years, according to a retrospective study findings including 8,467 adult patients with ALL who underwent their first alloHCT between 1990 and 2019. The researchers found that non-relapse mortality (NRM) improved in each disease stage: first complete remission (CR), subsequent CR, and non-CR. despite changes such as the expansion of alloHCT indications for elderly patients due to the development of reduced-intensity conditioning, introduction of pediatric-inspired intensive chemotherapy to adult ALL, and the increase in the number of alloHCT to intractable cases due to the expansion of donor sources (i.e., cord blood and HLA-haploidentical donors), NRM was steadily improved over the past 30 years. Improvements happened even though these changes can lead to an increase in NRM. (ref. Nishiwaki S, Akahoshi Y, Morita-Fujita M, et al. Improvements in allogeneic hematopoietic cell transplantation outcomes for adults with ALL over the past 3 decades [published online 2022 June 23]. Blood Adv. doi: 10.1182/bloodadvances.2022008032).
Kite, a Gilead Company (Nasdaq: GILD), today announced that the European Commission has approved its CAR T-cell therapy Tecartus® (brexucabtagene autoleucel) for the treatment of adult patients 26 years of age and above with relapsed or refractory (r/r) B-cell precursor acute lymphoblastic leukemia (ALL).
The approval is supported by data from the ZUMA-3 international multicenter, single-arm, open-label, registrational Phase 1/2 study of adult patients (≥18 years old) with relapsed or refractory ALL. This study demonstrated that 71% of the evaluable patients (n=55) achieved CR or CR with incomplete hematological recovery (CRi) with a median follow-up of 26.8 months. In an extended data set of all pivotal dosed patients (n=78) the median overall survival for all patients was more than two years (25.4 months) and almost four years (47 months) for responders (patients who achieved CR or CRi). Among efficacy-evaluable patients, median duration of remission was 18.6 months. (Press release https://www.kitepharma.com/news/press-releases/2022/9/kites-car-t-cell-therapy-tecartus-granted-european-marketing-authorization-for-the-treatment-of-relapsed-or-refractory-acute-lymphoblastic-leukemia)
Patients with ALL are at increased risk of thrombotic and/or bleeding events during early chemotherapy, especially when receiving asparaginase. D-dimer is a marker of fibrinolysis that has been associated with thrombotic risk in solid cancers and acute myeloid leukemia; however, to date, no ALL-based study has assessed D-dimer level and risk for thrombosis. (Ref. https://doi.org/10.1182/bloodadvances.2022007699)
ASH – Innovations in Leukemia –> Click here
EHA – Hemasphere –> Click here
Interesting study in Multiple Myeloma on carer perceptions and QoL. Something ALAN is also looking in to. Article here.
Virtual geriatric assessment is a hot topic in the field of geriatrics, but objective function measures are difficult to achieve via telehealth. In this report, DuMontier and colleagues report on their experience trying to incorporate objective function measures done virtually. The authors developed a virtual frailty assessment for older adults with hematologic malignancies that incorporates patient-reported and objective-performance measures. They found that virtual assessments detect less frailty when compared to in-person visits, but they are safe, feasible, and may provide significant advantages for care depending on situations and circumstances. Article here