KU Leukemia Treatment and Management Research Paper

Topic of interest: Leukemia Treatment and Management.Articles:
1. Development of a dried blood spot sampling method towards therapeutic
monitoring of radotinib in the treatment of chronic myeloid leukaemia
Citation:
Lee, J., Jung, S. Y., Choi, M., Park, J., Park, S., Lim, S., Cho, K. H., Oh, S. Y.,
Ha, J., Kim, D., & Lee, J. (2020). Development of a dried blood spot sampling
method towards therapeutic monitoring of radotinib in the treatment of chronic
myeloid leukaemia. Journal of Clinical Pharmacy and Therapeutics, 45(5),
1006–1013. https://doi.org/10.1111/jcpt.13124
2. Treatment of Relapsed Acute Myeloid Leukemia
Citation:
Thol, F., & Ganser, A. (2020). Treatment of relapsed acute myeloid leukemia.
Current Treatment Options in Oncology, 21(8). https://doi.org/10.1007/s11864020-00765-5
3. Quality of life among chronic myeloid leukemia patients in the second‑line
treatment with nilotinib and infuential factors
Citation:
Nguyen, C. T. T., Nguyen, B. T., Nguyen, T. T. T., Petrelli, F., Scuri, S., &
Grappasonni, I. (2021). Quality of life among chronic myeloid leukemia
patients in the second-line treatment with nilotinib and influential factors.
Quality of Life Research. https://doi.org/10.1007/s11136-021-02952-9
4. Management of Chronic Myeloid Leukemia in Advanced Phase
Citation:
Bonifacio, M. (2019). Management of Chronic Myeloid Leukemia in Advanced
Phase. Frontiers. Retrieved October 11, 2022, from
https://www.frontiersin.org/articles/10.3389/fonc.2019.01132/full
5. How I treat acute myeloid leukemia in the era of new drugs
Citation:
DiNardo, C. D., & Wei, A. H. (2020). How I treat acute myeloid leukemia in the
era of new drugs. Blood, 135(2), 85-96.
https://ashpublications.org/blood/article/135/2/85/428884/How-I-treat-acutemyeloid-leukemia-in-the-era-of
Summaries
1. Dried blood spot (DBS) sampling is a minimally invasive method of blood
sampling that enables the monitoring of drug concentrations to be more
convenient. This study aimed to develop a DBS sampling method for an accurate
and precise prediction of radotinib plasma concentrations (Cp) in patients with
chronic myeloid leukemia (CML). Dried blood spots and venous blood samples
were simultaneously collected from fifty CML patients who had been receiving
radotinib for at least a week. Radotinib concentrations were measured using a
high-performance liquid chromatographic method with tandem mass spectrometric
detection. Unmeasured Cp was predicted directly based on a Deming regression
between DBS concentrations (CDBS) and Cp. Unmeasured Cp was also predicted
from CDBS corrected by each patient’s hematocrit (Hct). Both prediction methods
were evaluated for their accuracy and precision using Deming regression and
Bland-Altman analysis. The Deming regression equation between CDBS and Cp
was obtained as follows: Cp = 1.34∙CDBS + 4.26 (r2 = .97). Cp was directly
predictable using Cp, pred1 = 1.34∙CDBS + 4.26. With Hct correction, Cp was
alternatively predictable using Cp, pred2 = CDBS/ (1–Hct + Hct2). The slopes of
the Deming regression line between predicted and measured Cp were 0.99 and
1.02 for the direct and Hct-corrected methods, respectively. The mean biases
(accuracy) were −0.44% and 1.6% with the 95% limits of agreement (precision) of
−22.4% to 21.5% and −20.5% to 23.7%, respectively. More than 93% of predicted
and measured Cp pairs had their differences within 20% of the mean of each pair
in both methods. Radotinib CDBS are highly correlated with radotinib Cp.
Radotinib Cp can be accurately and precisely predicted from CDBS using direct or
Hct-corrected prediction methods. Both appear to be appropriate for the
therapeutic monitoring of radotinib in patients with CML.
2. R/R AML remains a common clinical scenario with poor outcomes. HSCT is
necessary for long-term remission and survival. Due to the limited treatment
options in relapsed patients, clinical trials are the first choice of therapy. For
FLT3- and IDH1-/IDH2-mutated AML patients, targeted therapies have shown
results superior to standard therapy. The FDA has approved gilteritinib for FLT3-
mutated AML as well as ivosidenib/enasidenib for IDH1-/IDH2-mutated r/r AML
patients. Monotherapy with venetoclax, a bcl-2 inhibitor, has moderate efficacy in
r/r AML. However, early results in combination with intensive chemotherapy or
HMA are very encouraging. Trials combining novel substances with each are
necessary. The development of cellular therapies such as CAR-T cells or
bispecific T cell engager antibody constructs is very demanding in AML as it is
difficult to identify the ideal target structure on AML blasts.
3. This study aims to evaluate the quality of life (QoL) of chronic myeloid leukemia
(CML) patients prescribed with nilotinib as a second-line therapy and explores the
influential factors. A multicenter retrospective survey was conducted via face-toface interviews based on the EORTC QLQ-C30 questionnaire. A total of 121 adult
CML patients resistant to imatinib and used nilotinib for at least 3 months were
enrolled. The influential features were assessed by multiple linear regression
models. Patients had the mean age of 47.49 (SD = 13.67) years, dominated by
middle-aged and male groups. The mean scores of functions ranged from 75 to 83,
and those of symptoms were from 5 to 28, with the highest of fatigue (28.28),
insomnia (22.87), and pain (21.07). The mean global health status/QoL score was
67.70 (SD = 16.80) with considerable financial difficulties (52.34 (SD = 32.15)).
Male patients reported higher functional scores and fewer symptoms compared
with female patients. All aspects of QoL became worse with increasing age.
Besides age and gender, level of education, duration of nilotinib usage, and
comorbidities were also significantly influential factors in many QoL domains. A
predicted model for expected mean scores of QoL domains was built based on
these factors. The CML patients treated with nilotinib had the above-moderate
QoL scores, a light decrease of functional scores, great financial difficulties, and
still experienced symptoms. Strategies and more therapeutic considerations to
enhance QoL for CML patients targeted toward women, the old, low educational
level, and long duration of nilotinib usage, and many comorbidities are needed in
the setting.
4. Management of CML in advanced phase remains challenging. However, prognosis
for patients diagnosed in AP improved clearly over years, and presently most
patients with AP features at diagnosis can be managed as high-risk CP patients.
Patients in blast crisis have inferior outcomes due to emergent resistance to TKI.
Rational combination of TKI and chemotherapy or, preferably, novel agents
including immunotherapy could improve remission rates and duration. Frontline
imatinib results challenged the concept of transplantation in CP-CML patients;
nowadays the use of more potent TKI might modify the same concept also in
patients presenting with advanced disease. However, optimal management of
patients in CP represents the best way to avoid disease evolution and to allow a
quite normal life duration for all patients. Due to the limited evidence and the still
numerous unmet needs, it would be desirable that a dedicated expert panel would
provide updated recommendations for the management of CML in advanced
phase.
5. The treatment landscape of AML is undergoing unprecedented change, with no
fewer than 8 new drug approvals since 2017. Our treatment paradigm has shifted
away from a simple binary distinction between “curative, intensive therapy” and
“palliative, lower intensity” approaches. Instead, the increased diversity of
therapeutic options requires a more nuanced treatment algorithm that incorporates
mutation-specific targeted therapies, monoclonal antibodies, and apoptosisinducing small molecules, in addition to improved liposomal delivery of standard
therapies. We fully expect and sincerely hope that our review of “new drugs” will
be antiquated in the next few years due to the rapid pace of clinical development
and abundance of newly approved therapies. We highlight caution, however, in an
unrestrained combination of these new drugs outside of the context of clinical
trials, as prevention of unanticipated severe drug-induced toxicities is imperative.
Carefully conducted clinical studies that report on the safety of new combinations,
supported by correlative studies illuminating mechanisms of response and
resistance, will be critical to ensure that future progress is safe for patients and
supported by a strong body of scientific evidence.