A Personalized Risk Model for Azacitidine Outcome in Myelodysplastic Syndrome and Other Myeloid Neoplasms Identified by Machine Learning Model Utilizing Real-World Data.

Azacitidine is an approved therapy for higher-risk myelodysplastic syndrome (MDS). However, only 30-40% patients respond to azacitidine, and the responses may take up to six cycles to become evident. Delayed responses and the myelosuppressive effects of azacitidine make it challenging to predict which patients will benefit. This is further compounded by a lack of uniform prognostic tools to identify patients at risk of early treatment failure. Hence, we performed a retrospective analysis of 273 consecutive azacytidine-treated patients. The median overall survival was 16.25 months with only 9% alive at 5 years. By using pre-treatment variables incorporated into a random forest machine learning model, we successfully identified those patients unlikely to benefit from azacytidine upfront (7.99 vs. 22.8 months, p < 0.0001). This model also identified those who required significantly more hospitalizations and transfusion support. Notably, it accurately predicted survival outcomes, outperforming the existing prognostic scoring system. By integrating somatic mutations, we further refined the model and identified three distinct risk groups with significant differences in survival (5.6 vs. 10.5 vs. 43.5 months, p < 0.0001). These real-world findings emphasize the urgent need for personalized prediction tools tailored to hypomethylating agents, reducing unnecessary complications and resource utilization in MDS treatment.

A national service for delivering CD19 CAR-Tin large B-cell lymphoma - The UK real-world experience.

CD19 CAR-T have emerged as a new standard treatment for relapsed/refractory (r/r) large B-cell lymphoma (LBCL). CAR-T real-world (RW) outcomes published to date suggest significant variability across countries. We provide results of a large national cohort of patients intended to be treated with CAR-T in the UK. Consecutive patients with r/r LBCL approved for CAR-T by the National CAR-T Clinical Panel between December 2018 and November 2020 across all UK CAR-T centres were included. 404/432 patients were approved [292 axicabtagene ciloleucel (axi-cel), 112 tisagenlecleucel (tisa-cel)], 300 (74%) received the cells. 110/300 (38.3%) patients achieved complete remission (CR) at 6 months (m). The overall response rate was 77% (52% CR) for axi-cel, 57% (44% CR) for tisa-cel. The 12-month progression-free survival was 41.8% (axi-cel) and 27.4% (tisa-cel). Median overall survival for the intention-to-treat population was 10.5 m, 16.2 m for infused patients. The incidence of grade ≥3 cytokine release syndrome and neurotoxicity were 7.6%/19.6% for axi-cel and 7.9%/3.9% for tisa-cel. This prospective RW population of CAR-T eligible patients offers important insights into the clinical benefit of CD19 CAR-T in LBCL in daily practice. Our results confirm long-term efficacy in patients receiving treatment similar to the pivotal trials, but highlight the significance of early CAR-T failure.

The treatment landscape for Relapsed Refractory B Acute Lymphoblastic Leukaemia (ALL).

The last eight years have seen a rapid expansion of salvage options for patients with relapsed refractory (RR) acute lymphoblastic leukemia (ALL). The efficacy of targeted approaches with blinatumomab and Inotuzumab ozogamicin (InO), outweigh that of conventional chemotherapeutic regimens, and the reduced toxicity profile has also translated into higher transplant realization rates. Factors influencing the sequential use of these two antibodies include the preference for InO in those with high disease burden, while blinatumomab is a superior agent for attaining MRD responses in low disease burden groups. InO should not be used first in those with significant liver disease. Most impressive is the advent of chimeric antigen receptor cell therapy (CAR-T), a curative therapy in a significant proportion of younger patients with RR-ALL. Careful consideration is now required in the selection of relapse therapies; this review summarizes current available strategies and how to navigate the treatment landscape for RR ALL.

Clinical impact of NPM1-mutant molecular persistence after chemotherapy for acute myeloid leukemia.

Monitoring of NPM1 mutant (NPM1mut) measurable residual disease (MRD) in acute myeloid leukemia (AML) has an established role in patients who are treated with intensive chemotherapy. The European LeukemiaNet has defined molecular persistence at low copy number (MP-LCN) as an MRD transcript level <1% to 2% with a <1-log change between any 2 positive samples collected after the end of treatment (EOT). Because the clinical impact of MP-LCN is unknown, we sought to characterize outcomes in patients with persistent NPM1mut MRD after EOT and identify factors associated with disease progression. Consecutive patients with newly diagnosed NPM1mut AML who received ≥2 cycles of intensive chemotherapy were included if bone marrow was NPM1mut MRD positive at the EOT, and they were not transplanted in first complete remission. One hundred patients were followed for a median of 23.5 months; 42% remained free of progression at 1 year, either spontaneously achieving complete molecular remission (CRMRD-; 30%) or retaining a low-level NPM1mut transcript (12% for ≥12 months and 9% at last follow-up). Forty percent met the criteria for MP-LCN. Preemptive salvage therapy significantly prolonged relapse-free survival. Risk factors associated with disease progression were concurrent FLT3-internal tandem duplication at diagnosis and suboptimal MRD response (NPM1mut reduction <4.4-log) at EOT.

Outcomes and health care utilization of older patients with acute myeloid leukemia.

BACKGROUND: The incidence of acute myeloid leukemia (AML) in older patients is increasing, but practice guidelines balancing quality-of-life, time outside of hospital and overall survival (OS) are not established. METHODS: We conducted a retrospective analysis comparing time outside hospital, OS and end-of-life care in AML patients ≥60 years treated with intensive chemotherapy (IC), hypomethylating agents (HMA) and best supportive care (BSC) in a tertiary hospital. RESULTS: Of 201 patients diagnosed between 2005 and 2015, 54% received IC while 14% and 32% were treated with HMA and BSC respectively. Median OS was significantly higher in patients treated with IC and HMA compared with BSC (11.5 versus 16.2 versus 1.3 months; p < .0001). Median number of hospital admissions for the entire cohort was 3 (1-17) and patients spent <50% of their life after the diagnosis in the hospital setting. Compared to BSC, IC (HR 0.27, p < .0001) and HMA therapy (HR 0.16, p < .0001) were associated with the lower likelihood of spending at least 25% of survival time in hospital. Although 66% patients were referred to palliative care, the interval between referral to death was 24 (1-971) days and 46% patients died in the hospital. CONCLUSION: Older patients with AML, irrespective of treatment, require intensive health care resources, are more likely to die in hospital and less likely to use hospice services. Older AML patients treated with disease modifying therapy survive longer than those receiving BSC, and spend >50% of survival time outside the hospital. These data are informative for counselling older patients with AML.