Robert Peter Gale

People with acute myeloid leukaemia with normal cytogenetics (CN-AML) have diverse outcomes explained in part by different mutation topographies [1-3]. DDX11 encodes ChlR1, an ATP-dependent DNA helicase important in DNA damage repair and other cell processes which maintaining genomic integrity [4]. Biallelic DDX11 mutations result in a rare autosomal recessive disorder, Warsaw breakage syndrome [5]. Somatic DDX11 mutations are reportedly associated with poor survival in myelodysplastic syndrome (MDS) and lymphoid cancers [6]. However, there are few data on the impact of DDX11 mutations on outcomes in AML.We interrogated data from 1358 consecutive subjects with newly-diagnosed AML at Peking University PeopleLs Hospital from May, 2010 to December, 2019. AML was diagnosed by histology, immunology, cytogenetics and genetic abnormalities as described [7]. Inclusion criteria …

There is considerable interest in and enthusiasm for quantitative tests for residual cancer cells in the context of cancer therapy, a concept referred to as measurable residual disease (MRD)-testing. However, an updated critical evaluation of using MRD-tests to predict cancer recurrence and to direct subsequent cancer therapy (ies) is needed. We review concepts underlying MRD-testing and results of studies of MRD-testing in haematological and solid cancers. Most important, we examine if there are any convincing data proving therapy decisions in someone with cancer should be guided by results of MRD-testing or a positive MRD-test result provides sufficient and meaningful lead time to intervene and substantially change clinical outcomes.

Objective Ruxolitinib was recently approved to treat corticosteroid‐resistant acute graft‐versus‐host disease (GvHD). However, it is unknown as to whether starting ruxolitinib at a lower versus higher acute GvHD grade or earlier versus later affected outcomes. This study identified the impact of starting acute GvHD grade and start time after declaring corticosteroid resistance and the effect on complete and overall response rates to ruxolitinib therapy. Methods Retrospective, observational multi‐center study. We divided cohorts into starting ruxolitinib ≤ 7 days (N = 45) versus at > 7 days after declaring corticosteroid resistance (N = 24). Results In ≤ 7 days cohort complete response (CR) rates at day 28 were 69% (54, 81%) versus 25% (11, 47%; p = .001) in > 7 days cohort, and overall response (OR) rates were 91% (78, 96%) versus 80% (48, 92%; p = .25). Conclusions Our data suggest that starting ruxolitinib in …

Most new drug approvals are based on data from large randomized clinical trials (RCTs). However, there are sometimes contradictory conclusions from seemingly similar trials and generalizability of conclusions from these trials is limited. These considerations explain, in part, the gap between conclusions drawn from data of RCTs and those from registries termed real world data (RWD). Recently, real-world evidence (RWE) drawn from RWD processed by artificial intelligence has received increasing attention. We describe the potential of using RWD in haematology concluding RWE from RWD may complement data from RCTs to support regulatory decisions.

B-cell acute lymphoblastic leukaemia (B-cell ALL) is a common haematologic cancer in children and adults. About 10 percent of children and 50 percent of adults fail to achieve a histological complete remission or subsequently relapse despite current anti-leukaemia drug therapies and/or haematopoietic cell transplants. Several new immune therapies including monoclonal antibodies and chimeric antigen receptor (CAR)-T-cells are proved safe and effective in this setting. We review data on US Food and Drug Administration (FDA)-approved immune therapies for B-cell ALL in children and adults including blinatumomab, inotuzumab ozogamicin, tisagenlecleucel, and brexucabtagene autoleucel. We also summarize pharmaco-dynamics, pharmaco-kinetics, and pharmaco-economics of these interventions.

Chronic myeloid leukemia with a BCR:: ABL1 b2a3 transcript is difficult to detect by conventional polymerase chain reaction (PCR). This can result in an incorrect diagnosis. We report a man with typical features of chronic myeloid leukemia but with a negative conventional PCR test for BCR:: ABL1 in whom we identified a BCR:: ABL1 fusion gene by fluorescence in situ hybridization and PCR with custom BCR and ABL1 primers.

Enthusiasm does not mitigate the potential problem of survivorship bias. The likelihood of therapy-free remission (TFR) reflects the biology of someone’s leukaemia and efficacy of tyrosine kinase inhibitor (TKI)-therapy. For every person A eligible to enroll in the EURO-SKI trial there was a person B who might never achieve deep molecular response (DMR) regardless of the duration of TKI-therapy [1, 2]. Likewise, for every person C able to maintain DMR for a prolonged interval and then achieve TFR there was another person D who could never achieve any of these endpoints because he/she had a DMR which was subsequently lost.Considering persons A, B, C, D, we conclude the EURO-SKI trial does not provide guidelines for optimizing the duration of anyone’s TKI-therapy or DMR. The authours made no such claim. Because no one like person B enrolled in EURO-SKI (inclusion criteria) EURO-SKI is silent on B …

Myelofibrosis is a myeloid neoplasm characterised by the presence of JAK2, CALR, or MPL mutations (with a 90% mutation frequency) and trilineage myeloid proliferation with prominent megakaryocyte atypia. People with myelofibrosis have a lower survival rate and poorer quality of life than healthy individuals. Therapy for myelofibrosis uses Janus kinase inhibitors, which reduce splenomegaly and alleviate symptoms. Regulatory approvals for Janus kinase inhibitors have focused on this dual endpoint. In this Viewpoint, we discuss the validity of using spleen reduction as a surrogate endpoint for the disease-modifying activity of candidate drugs for myelofibrosis. We suggest alternative endpoints addressing unmet patient needs, including progression-free survival and overall survival. Moreover, we highlight the importance of selecting a core set of crucial outcomes with which we can individualise clinical decision …