scholarly journals The New ELN Recommendations for Treating CML

2020 ◽  
Vol 9 (11) ◽  
pp. 3671
Author(s):  
Rüdiger Hehlmann
Keyword(s):  
Kinase Inhibitors ◽  
Chronic Phase ◽  
Cost Effective ◽  
Low Grade ◽  
Molecular Response ◽  
First Line ◽  
Term Survival ◽  
First Line Therapy ◽  
Line Therapy

After normal survival has been achieved in most patients with chronic myeloid leukemia (CML), a new goal for treating CML is survival at good quality of life, with treatment discontinuation in sustained deep molecular response (DMR; MR4 or deeper) and treatment-free remission (TFR). Four tyrosine kinase inhibitors (TKIs) have been approved for first-line therapy: imatinib, dasatinib, nilotinib, bosutinib. Unexpectedly, the outcome of long-term randomized trials has shown that faster response as achieved by higher doses of imatinib, imatinib in combination, or second-generation (2G)-TKIs, does not translate into a survival advantage. Serious and frequent, and in part cumulative long-term toxicities, have led to a reevaluation of the role of 2G-TKIs in first-line therapy. Generic imatinib is the current most cost-effective first-line therapy in the chronic phase. A change of treatment is recommended when intolerance cannot be ameliorated or molecular milestones are not reached. Patient comorbidities and contraindications of all TKIs must be considered. Risk profile at diagnosis should be assessed with the EUTOS score for long-term survival (ELTS). Monitoring of response is by polymerase chain reaction (PCR). Cytogenetics is still required in the case of atypical translocations, atypical transcripts, and additional chromosomal aberrations. TKIs are contraindicated during pregnancy. Since the majority of patients are at risk of lifelong exposure to TKIs, amelioration of chronic low-grade side effects is important.

scholarly journals Cost-Effectiveness of Pembrolizumab Plus Chemotherapy Versus Pembrolizumab Monotherapy in Metastatic Non-Squamous and Squamous NSCLC Patients With PD-L1 Expression ≥ 50%

2022 ◽  
Vol 12 ◽  
Author(s):  
Qiao Liu ◽  
Zhen Zhou ◽  
Xia Luo ◽  
Lidan Yi ◽  
Liubao Peng ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Life Expectancy ◽  
Cost Effective ◽  
Base Case ◽  
First Line ◽  
Term Survival ◽  
First Line Therapy ◽  
Line Therapy ◽  
Nsclc Patients

Objective To compare the cost-effectiveness of the combination of pembrolizumab and chemotherapy (Pembro+Chemo) versus pembrolizumab monotherapy (Pembro) as the first-line treatment for metastatic non-squamous and squamous non-small-cell lung cancer (NSCLC) with PD-L1expression ≥50%, respectively, from a US health care perspective.Material and Methods A comprehensive Makrov model were designed to compare the health costs and outcomes associated with first-line Pembro+Chemo and first-line Pembro over a 20-years time horizon. Health states consisted of three main states: progression-free survival (PFS), progressive disease (PD) and death, among which the PFS health state was divided into two substates: PFS while receiving first-line therapy and PFS with discontinued first-line therapy. Two scenario analyses were performed to explore satisfactory long-term survival modeling.Results In base case analysis, for non-squamous NSCLC patients, Pembro+Chemo was associated with a significantly longer life expectancy [3.24 vs 2.16 quality-adjusted life-years (QALYs)] and a substantially greater healthcare cost ($341,237 vs $159,055) compared with Pembro, resulting in an ICER of $169,335/QALY; for squamous NSCLC patients, Pembro+Chemo was associated with a slightly extended life expectancy of 0.22 QALYs and a marginal incremental cost of $3,449 compared with Pembro, resulting in an ICER of $15,613/QALY. Our results were particularly sensitive to parameters that determine QALYs. The first scenario analysis yielded lower ICERs than our base case results. The second scenario analysis founded Pembro+Chemo was dominated by Pembro.Conclusion For metastatic non-squamous NSCLC patients with PD-L1 expression ≥50%, first-line Pembro+Chemo was not cost-effective when compared with first-line Pembro. In contrast, for the squamous NSCLC patient population, our results supported the first-line Pembro+Chemo as a cost-effective treatment. Although there are multiple approaches that are used for extrapolating long-term survival, the optimal method has yet to be determined.

scholarly journals Primary Pelvic Exenteration for Advanced Gynaecological Malignancies

2020 ◽  
Vol 25 (2) ◽  
pp. 52-54
Author(s):  
Dragoș Constantin Cucoranu ◽  
Raluca Niculescu ◽  
Mihai Emil Căpîlna
Keyword(s):  
Pelvic Exenteration ◽  
Levator Ani ◽  
First Line ◽  
Term Survival ◽  
First Line Therapy ◽  
Line Therapy ◽  
Pelvic Malignancies ◽  
Advanced Stages ◽  
Gynaecological Malignancies

AbstractIntroduction: Indication of primary pelvic exenteration, without previous radiotherapy, is questionable in advanced stages of gynaecological malignancies.Materials and Methods: 24 patients who underwent primary pelvic exenteration for pelvic malignancies were studied retrospectively. The indications were cervical (n=17), vaginal (n=4), bladder (n=2) and endometrial cancer (n=1).Results: According to the type of exenteration, 14 were anterior and 10 total. Relying on the resection lines in relation with levator ani muscles, 14 were supralevatorial and 10 infralevatorial, of which five involved vulvectomy. Early complications occurred in 7 patients with 1 perioperative death.Conclusions: Primary pelvic exenterantion as first line therapy for advanced gynaecological malignancies can lead to long-term survival and it can even be curative in suitable selected patients. Still, postoperative complications are frequent, which can be lethal.

scholarly journals Efficacy and safety of Bosutinib in Patient with Chronic myeloid leukemia who was intolerant to DASTANIB,NILOTUNIB -Case report

2021 ◽  
Author(s):  
Abdullah Mohammad Arshad ◽  
mohamed yassin
Keyword(s):  
Case Report ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Molecular Response ◽  
Efficacy And Safety ◽  
Major Molecular Response ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

Bosutinib is approved as first line therapy for treatment of chronic phase CML and also in patients who are either resistant or intolerant to previous TKI. We present a 59 year old male who was intolerant to 2 TKI but showed excellent hematological and major molecular response to Bosutinib.

scholarly journals Comparison of the Clinical Outcomes of Nilotinib and Dasatinib Therapies in Newly Diagnosed Patients in the Chronic Phase of Chronic Myeloid Leukemia: A Retrospective Analysis

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4268-4268
Author(s):  
Noriyoshi Iriyama ◽  
Kei-Ji Sugimoto ◽  
Eriko Sato ◽  
Tomoiku Takaku ◽  
Michihide Tokuhira ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Research Funding ◽  
Chronic Phase ◽  
Scoring Systems ◽  
Molecular Response ◽  
First Line ◽  
Molecular Responses ◽  
Once Daily ◽  
First Line Therapy ◽  
Line Therapy

Abstract Background and Aim: Treatment with a tyrosine kinase inhibitor (TKI) is the standard of care for patients with chronic myeloid leukemia (CML). Based on the results of the ENESTnd and DASISION studies, the European LeukemiaNet 2013 guidelines now recommend the use of TKIs, imatinib (400 mg once daily), nilotinib (300 mg twice daily), and dasatinib (100 mg once daily) as first-line treatment for patients with CML in the chronic phase (CML-CP). Compared to imatinib, the new generation TKIs, nilotinib and dasatinib, were found to have deeper and faster treatment response rates with acceptable toxicities. However, a direct comparison between nilotinib and dasatinib has never been reported previously. Our study aims to compare the outcomes and molecular responses achieved following the first-line use of these two agents in patients with CML-CP. Patients and Methods: The database of the CML Cooperative Study Group, which includes patients who were initially diagnosed with CML after the introduction of imatinib (April 2001), was reviewed, and patients who were given nilotinib or dasatinib as first-line therapy were identified. The event-free survival (EFS, defined as the loss of treatment efficacy, disease progression, or any cause of death), and rates of cumulative major molecular response (MMR), and deep molecular response (DMR, defined as the depth of MR 4.5) were compared between the nilotinib and dasatinib groups. Further, the predictive ability of the Sokal, Hasford, and European Treatment and Outcome Study (EUTOS) scoring systems for the achievement of molecular responses was also evaluated. For the analysis of molecular responses, patients who switched from their initial treatment agent to another TKI before achievement of MMR or DMR were considered to have no MMR or DMR. Results and Discussion: Out of 361 patients with CML-CP enrolled in our database, 58 and 63 were treated with conventional doses of nilotinib (300 mg twice daily) and dasatinib (100 mg once daily), respectively, as first-line therapy. Patients who had been started on a low dose TKI therapy were excluded from this analysis. The patient demographics, including age, sex, observation periods, and the Sokal, Hasford, and EUTOS scores did not show significant differences between the groups. In total, there were five events during the observation period (1 in the nilotinib group and 4 in the dasatinib group), and all events were deaths unrelated to CML, except for one in a patient in the dasatinib group who showed loss of complete cytogenetic response. The disease did not progress to the accelerated or blastic phase in any of the cases. The EFS did not differ between these two groups (p = 0.214). The MMR rates by 6, 12, 18, and 24 months were 59%, 72%, 74%, and 81%, respectively, in the nilotinib group and 52%, 73%, 81%, and 86%, respectively, in the dasatinib group. The DMR rates by 6, 12, 18, and 24 months was 7%, 17%, 24%, and 28%, respectively, in the nilotinib group and 3%, 16%, 25%, and 29%, respectively, in the dasatinib group. During the first 24 months of treatment, 4 (7%) patients in the nilotinib group and 11 (17%) in the dasatinib group had been switched to other TKIs (p = 0.0983). Among the three scoring systems, only the Hasford score could predict the achievement of DMR, and all of them failed to predict the achievement of MMR in the entire cohort. Our data suggest that both nilotinib and dasatinib have comparable efficacies, with high molecular response rates and promising outcomes. The validity of our findings should be tested in a randomized study, which is currently underway in Japan. Disclosures Takaku: Bristol-Myers Squibb: Honoraria, Speakers Bureau; Novartis Pharma K.K.: Honoraria, Speakers Bureau. Tokuhira:Mitsubishi Tanabe Pharma Corporation: Speakers Bureau; Bristol-Myers Squibb: Speakers Bureau; AYUMI Pharmaceutical Corporation: Speakers Bureau; Chugai: Speakers Bureau. Asou:Eisai Co., Ltd.: Research Funding; SRL Inc.: Consultancy; Yakult Honsha Co., Ltd.: Speakers Bureau; Kyowa Hakko Kirin Co., Ltd.: Speakers Bureau; Asahi Kasei Pharma Co., Ltd.: Research Funding; Astellas Pharma Inc.: Research Funding; Sumitomo Dainippon Pharma Co., Ltd.: Research Funding; Chugai Pharmaceutical Co., Ltd.: Research Funding. Kizaki:Nippon Shinyaku,: Research Funding, Speakers Bureau; Celgene: Research Funding, Speakers Bureau; Bristol-Myers Squibb: Research Funding, Speakers Bureau; Novartis: Speakers Bureau. Kawaguchi:Novartis Pharma K.K.: Honoraria, Speakers Bureau; Bristol-Myers Squibb: Honoraria, Speakers Bureau; Alexion: Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau.

Is Major Molecular Response a Safe Haven Against Blast Crisis in Cml Patients Treated with Imatinib?

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3760-3760
Author(s):  
Pratap Neelakantan ◽  
Dragana Milojkovic ◽  
Gareth Gerrard ◽  
Letizia Foroni ◽  
Jane Apperley ◽  
...  
Keyword(s):  
Median Time ◽  
Research Funding ◽  
Chronic Phase ◽  
Molecular Response ◽  
Major Molecular Response ◽  
First Line ◽  
Blast Phase ◽  
Blastic Transformation ◽  
First Line Therapy ◽  
Line Therapy

Abstract Abstract 3760 The introduction of tyrosine kinase inhibitors (TKIs) has proved to be a major advance in the management of patients with chronic myeloid leukemia in chronic phase (CML-CP) although the clinical benefit seems to be limited to those patients who achieve complete cytogenetic remission (CCyR). Patients who achieve CCyR are believed to have an excellent prognosis, but a very small proportion of those patients may lose the response and progress to blastic phase. In this work we studied a cohort of 210 patients who achieved CCyR (142 of them were in MMR) on imatinib as first line therapy in order to identify the incidence of blastic transformation in this population. Between June 2000 and December 2010, 282 consecutive adult patients with CML-CP were seen at our institution, of whom, 210 achieved CCyR on imatinib 400 mg daily as first-line therapy. The median follow-up was 69 months. Of the 210 patients in CCyR, 5 (2.3%) progressed to blastic transformation (BT) (3 myeloid and 2 lymphoid). The Sokal risk was low in 3 patients and intermediate in two. The median time to achievement of CCyR in these 5 patients was 18 months (range 9–20 months). Two of these patients also achieved a major molecular response (MR3), one achieved a 4 log reduction on the international scale and two patients had a CCyR with no MR3. The median time to achievement of MR3 (or better) in the three patients was 24 months (range 18–28 months). After achieving CCyR all 5 patients had progressive increases in their BCR-ABL1 transcript levels over a period of a few months leading to BT without an intervening accelerated phase. None of the patients had a ABL1 kinase domain mutation prior to transformation to advanced phase, but two patients subsequently developed a new mutation at the time of BT (M244V and T315I, respectively). The 8-year cumulative incidence (CI) of BT after reaching CCyR was 2.3% and was 2.8% when calculated from diagnosis (Figure 1). The median time from achieving CCyR to BT, was 18 months (range 12–40 months). The median time from the onset of an increase in BCR-ABL1 transcripts to BT was 6 months (range 4–7 months). All 5 patients had good compliance with TKIs. All 5 patients were treated by allogeneic stem cell transplantation after BT in their second chronic phase. One patient proceeded to a transplant after combination chemotherapy and TKI, but 4 others only received a TKI prior to transplant (3 dasatinib and 1 nilotinib). All 5 patients subsequently died due to transplant related causes. The 8-year CI of BT after attaining CCyR was 2.3%. MR3 does not appear to completely protect against BT as 3 of the 5 patients with MR3 lost the response and progressed to BT. In our series we could not identify a time point beyond which patients may be safe from blastic transformation, which continues to be a rare but catastrophic event in responding patients. Figure 1. (CI of progression to blast phase in patients who had previously attained CCyR, n=210). Figure 1. (CI of progression to blast phase in patients who had previously attained CCyR, n=210). Disclosures: Goldman: Novartis, Bristol Myers-Squibb, and Amgen: Honoraria. Marin:Novartis: Research Funding; BMS: Research Funding.

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