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Clinical lymphoma, myeloma & leukemia
Cancer Media Group
Clinical lymphoma, myeloma & leukemia

Cancer Media Group

2152-2650

Clinical lymphoma, myeloma & leukemia/Journal Clinical lymphoma, myeloma & leukemia
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    SOHO State of the Art Updates and Next Questions: Waldenstr?m Macroglobulinemia-2021 Update on Management and Future Directions

    Thomas, Sheeba K.
    9页
    查看更多>>摘要：Waldenstrom macroglobulinemia (WM) is a low-grade B-cell lymphoproliferative disorder. It is defined by having 10% bone marrow infiltration with lymphoplasmacytic cells and/or an immunoglobulin M (IgM) monoclonal gammopathy of >3g/dL. Risk factors include a personal history of IgM MGUS, and a family history of WM or a related disorder. Race, sex, and chronic antigen stimulation also appear to influence risk. Between 93 to 97% of patients with WM have a somatic mutation of the MYD88 gene. Of these, approximately 30% also have a mutation of CXCR4. The presence of a MYD88 mutation is associated with higher 10-year overall survival (90% vs. 73%; P < .001), while CXCR4 mutation status does not appear to have a similar effect. Based on consensus guidelines, WM patients with a disease-related hemoglobin level of less than 10g/dL, a platelet count of less than 100 ??10 9/L, bulky adenopathy or organomegaly, symptomatic hyperviscosity, severe neuropathy, amyloidosis, cryoglobulinemia, cold agglutinin disease, or evidence of disease transformation, should be considered for immediate therapy. Patients not meeting these cr iter ia may be observed, with monitoring at 3 to 6 month intervals. When treatment is warranted, combinations of rituximab with alkylat-ing agents and proteasome inhibitors are often effective, as are Bruton's tyrosine kinase (BTK) inhibitors and BCL-2 inhibitors. Selection among available regimens should take patients' gene mutation profile, disease-related features, and co-morbid conditions into account. Promising novel therapies in development include non-covalent BTK inhibitors, CXCR4 antagonists, BCL 2 inhibitors, bi-specific antibodies, radioimmunoconjugates, and CD19-and CD20-Targeted Chimeric Antigen Receptor T cells
      原文链接:
    • NSTL
    • Cig Media Group, Lp

    SOHO State of the Art Updates and Next Questions: What is Fitness in the Era of Targeted Agents?

    Frustaci, Anna MariaDeodato, MarinaZamprogna, GiuliaCairoli, Roberto...
    6页
    查看更多>>摘要：The importance of coexisting conditions in chronic lymphocytic leukemia (CLL) outcome has been increasingly recognized over the past years. The role of comorbidities to predict patients??? vulnerability toward immunochemotherapy has been well establish, especially since some of the tools commonly used to evaluate patients??? fitness were employed to determine treatment eligibility in randomized trials. Nevertheless, is it still unclear how much fitness weights on treatment outcome with targeted agents and which assessment should be preferred. There are key differences in the toxicity profile between novel agents that are getting much more evident in retrospective, real-life experiences, rather than clinical trials. Therefore, an individual patient???s comorbid medical conditions may be a deciding factor in therapy selection. Here, we analyze main evidence in literature on the predicting value of comorbidity assessment on outcome and management of CLL patients receiving novel agents.
      原文链接:
    • NSTL
    • Cig Media Group, Lp

    The Novel Therapeutic Landscape for Relapsed/Refractory Diffuse Large B Cell

    Nuvvula, SriDahiya, SaurabhPatel, Shyam A.
    11页
    查看更多>>摘要：Diffuse large B cell lymphoma (DLBCL) is an aggressive malignancy that has been traditionally treated with anthracycline-based chemotherapy, but approximately one-third of patients relapse after first-line therapy or have primary refractoriness. In this focused review, we discuss the 7 novel Food & Drug Administration (FDA)-approved medications for relapsed/refractory (R/R) DLBCL. We describe 5 CD19-targeted therapies, 3 of which are chimeric antigen receptor (CAR)-T cell therapies. We also highlight novel non???cell-based targeted therapies and discuss optimal sequencing considerations based on the goal of treatment, with an emphasis on CAR-T cell therapy as curative intent. We consider the limited tolerability of certain novel agents, prospects for elderly patients, and financial aspects of these approaches. We discuss advantages and limitations of these targeted therapies based on seminal clinical trials. Finally, we summarize ongoing trials involving promising agents making their way into the pharmacologic pipeline. These therapies include allogeneic CAR-T treatments and multi-antigen targeting therapies such as the CD19/CD22 CAR-T and the CD3/CD20 bispecific antibodies mosunetuzumab and odronextamab. We summarize our approach based on the best available evidence as we enter 2022.
      原文链接:
    • NSTL
    • Cig Media Group, Lp

    Characteristics and Clinical Outcomes of Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma Who Received At Least 3 Lines of Therapies

    Hamadani, MehdiLiao, LauraYang, TonyChen, Lei...
    9页
    查看更多>>摘要：Purpose: To examine outcomes of r/r DLBCL Methods: Retrospective study using COTA EHR database (2014 early 2020) Results: Majority of patients received pharmacological treatment in 3L and 4L; median OS times were 7.7 and 4.4 months, respectively. < 20% of patients received cell-based therapies; median OS time was not reached. Conclusion: There is an unmet need for more effective r/r DLBCL treatments. Introduction: The treatment landscape for diffuse large B-cell lymphoma (DLBCL) has recently changed. We examined characteristics and clinical outcomes of DLBCL patients who initiated a third (3L) and fourth (4L) line of therapy during a contemporary time frame. Materials and Methods: Adult patients diagnosed with DLBCL who received >= 3L after January 1, 2014 were selected from the COTA database. Patients were grouped into cohorts by 3L or 4L initiation and further stratified by type of treatment received: chemotherapy or chemoimmunotherapy (CT/CIT), targeted therapy (TT), chimeric antigen receptor T cells (CAR-T), or salvage therapy consolidated with hematopoietic cell transplant (HCT). Patient characteristics, response rates, and overall survival (OS) were examined. Results: Among adult patients with relapsed/refractory (r/r) DLBCL, 212 (mean age; 61.8 years; 59.0% male) received their 3L and 127 (mean age: 61.0 years; 61.4% male) their 4L. Among those treated with their 3L and 4L, 55.2% and 50.4%, respectively, received CT/CIT; 26.9% and 34.6% received TT. The complete response rate of 3L patients was 9.4% for CT/CIT, 10.5% for TT, and 60% for CAR-T. Similar findings were seen with 4L patients (CT/CIT: 6.3%; TT: 15.9%; CAR-T: 53.8%). For those who received pharmacological treatment in 3L and 4L, median OS times were 7.7 and 4.4 months, respectively. Median OS times of patients who received cell-based therapies (CAR-T/HCT) were not reached. Conclusion: In this study, a majority of r/r DLBCL patients were treated with CT/CIT or TT in 3L and 4L settings and had poor clinical outcomes, underscoring the need for more effective treatments. Clinical Lymphoma, Myeloma and Leukemia, Vol. 22, No. 6, 373-381 (c) 2021 Elsevier Inc. All rights reserved.
      原文链接:
    • NSTL
    • Cig Media Group, Lp

    Cost-Effectiveness of Shortening Treatment Duration Based on Interim PET Outcome in Patients With Diffuse Large B-cell Lymphoma

    Duehrsen, U.Huettmann, A.Schmitz, C.Lugtenburg, P. J....
    11页
    查看更多>>摘要：Guideline recommendations for diffuse large-B-cell lymphoma treatment are shifting from long to short treatment duration. Using a Markov model, we evaluated the cost-effectiveness of this shortening in treatment duration, separately in I-PET positive and I-PET negative patients. We showed that this shift is justified for I-PET negative patients, but not for I-PET positive patients as shortening treatment duration in these patients has harmful consequences. Background: Guideline recommendations for diffuse large-B-cell lymphoma (DLBCL) treatment are shifting from long to short treatment duration, although it is still unclear whether shortening treatment duration does not cause any harm. As interim PET (I-PET) has high negative predictive value for progression, we evaluated the cost-effectiveness of shortening treatment duration dependent on I-PET result. Materials and Methods: We developed a Markov cohort model using the PET Re-Analysis (PETRA) database to evaluate a long treatment duration (LTD) strategy, ie 8x R-CHOP or 6x R-CHOP plus 2 R, and a short treatment duration (STD) strategy, ie 6x R-CHOP. Strategies were evaluated separately in I-PET2 positive and I-PET2 negative patients. Outcomes included total costs and quality-adjusted life years (QALYs) per patient (pp) from a societal perspective. Net monetary benefit (NMB) per strategy was calculated using a willingness-to-pay threshold of euro 50,000/QALY. Robustness of model predictions was assessed in sensitivity analyses. Results: In I-PET2 positive patients, shortening treatment duration led to 50.4 additional deaths per 1000 patients. The STD strategy was less effective (-0.161 [95%CI:-0.343;0.028] QALYs pp) and less costly (- euro 2768 [95%CI: euro 8420; euro 1105] pp). Shortening treatment duration was not cost-effective (incremental NMB euro 5281). In I-PET2 negative patients, shortening treatment duration led to 5.0 additional deaths per 1000 patients and a minor difference in effective ness (-0.007 [95%CI:-0.136;0.140] QALY pp). The STD strategy was less costly (- euro 5807 [95%CI:- euro 10,724;- euro 2685] pp) and led to an incremental NMB of euro 5449, indicating that it is cost-effective to shorten treatment duration. Robustness of these findings was underpinned by deterministic and probabilistic sensitivity analyses. Conclusion: Treatment duration should not be shortened in I-PET2 positive patients whereas it is cost-effective to shorten treatment duration in I-PET2 negative patients.
      原文链接:
    • NSTL
    • Cig Media Group, Lp

    Differential Implications of CSF3R Mutations in t(8;21) and CEBPA Double Mutated Acute Myeloid Leukemia

    Wang, BiaoWen, LijunWang, ZhengChen, Suning...
    12页
    查看更多>>摘要：This study aimed to analyze the CSF3R mutations (CSF3R(mut)) in AML with recurrent genetic abnormalities for potential synergistic pathomechanism in 1102 adult de novo AML patients with available NGS information. A propensity score matching (PSM) followed by Kaplan-Meier method was applied to measure their prognostic effects. The CSF3R(mut) loci and types differed according to AML subtypes, with frameshift-indels and premature stop confined in the t(8;21) AML [10/12 (83.3%)], and missense recurrently aggregated in the CEBPAdm AML [16/16 (100%)]. After PSM followed by Kaplan-Meier analysis, CSF3R(mut) cases had comparable disease-free survival (DFS) and overall survival (OS) to those with CSF3R(wt) in the t(8;21) AML cohort. By contrast, CSF3R(mut) showed an inclination towards inferior DFS compared to CSF3R(wt) in the CEBPAdm AML cohort. CSF3R(mut) were frequently enriched in patients with t(8;21) and CEBPAdm subtypes among AML, but showed divergent clinicopathologic features, mutation loci and types and a differing prognostic aspects. More notably, either a primary induction failure (n = 2) or early relapse (n = 2, DFS = 2.5 and 5.6 months, respectively) was encountered in all of the 4 CEBPAdm cases carrying both WT1 and CSF3R co-mutations. Background: Few data are available exploring mutations of the colony-stimulating factor 3 receptor (CSF3R) in acute myeloid leukemia (AML) in an all-round and systematic manner. The purpose of this study was to analyze the CSF3R mutations (CSF3R(mut)) in AML with recurrent genetic abnormalities for potential synergistic pathomechanism. Patients and Methods: We retrospectively screened 1102 adult de novo AML patients with available next-generation sequencing (NGS) information on 132 genes related to hematologic disorders. The ??2, Mann-Whitney U tests were used to analyze their associations with clinicopathologic characteristics, and a propensity score matching (PSM) followed by Kaplan Meier method was applied to measure their prognostic effects. Results: Overall, CSF3R(mut) were detected in 40 (3.6%) of 1102 patients with adult de novo AML. CSF3R(mut) were predominantly enriched in AML with the CEBPA double mutations (CEBPAdm) (16/122, 13.1%), t(8;21) (12/186, 6.5%) and mutated RUNX1 (3/50, 6.0%), respectively. The CSF3R(mut) loci and types differed according to AML subtypes, with frameshift-indels and premature stop confined in the t(8;21) AML [10/12 (83.3%)], and missense recurrently aggregated in the CEBPAdm AML [16/16 (100%)]. Cases with CSF3R(mut) had a lower WBC count versus those with CSF3R wild-type (CSF3R(wt)) in the t(8;21) AML cohort, with a borderline significance [median 5.45 (range 0.94-20.30) x 10(9) /L) vs. 8.80 (range 0.96-155.00) x 10(9) /L, P = .046]. CSF3R(mut) were non-significantly associated with higher WBC counts [median 33.6 (range 6.8-287.6) x 10(9) /L vs. 18.1 (range 1.7196.0) x 10(9) /L, P = .156] and significantly with lower immunophenotypic CD15 positivity [0/8 (0%) vs. 44/80 (55%), P = .009] as compared to CSF3R(wt) in the CEBPAdm AML cohort. After propensity score matching followed by Kaplan-Meier analysis, CSF3R(mut) cases had comparable disease-free survival (DFS) and overall survival (OS) to those with CSF3R wt (P =.607 and P =.842, respectively) in the t(8;21) AML cohort. By contrast, CSF3R(mut) showed an inclination towards inferior DFS compared to CSF3R(wt) in the CEBPA(dm) AML cohort [median DFS 19.8 (95%CI 3.1-36.5) months vs. not reached (NR), P =.086]. No significant difference was found for OS between CSF3R(mut) and CSF3R(wt) cases (P =.943). Conclusion: We concluded that CSF3R(mut) were frequently enriched in patients with t(8;21) and CEBPA dm subtypes among AML, but showed divergent clinicopathologic features, mutation loci and types and differing prognostic aspects. Clinical Lymphoma, Myeloma and Leukemia, Vol. 22, No. 6, 393-404 (c) 2021 The Author(s). Published by Elsevier Inc.
      原文链接:
    • NSTL
    • Cig Media Group, Lp

    The Outcomes of Ponatinib Therapy in Patients With Chronic Myeloid Leukemia Resistant or Intolerant to Previous Tyrosine Kinase Inhibitors , Treated in Poland Within the Donation Program

    Sacha, TomaszSzczepanek, ElzbietaDumnicka, PaulinaGora-Tybor, Joanna...
    11页
    查看更多>>摘要：Ponatinib is a new pan-inhibitor of tyrosine kinase active in resistant chronic myeloid leukemia (CML). Evaluation of outcomes in 43 patients confirmed ponatinib efficacy in a significant proportion of subjects heavily pre-treated with tyrosine kinase inhibitors achieving durable responses in both chronic phase and accelerated/blastic phase CML groups. Introduction: Tyrosine kinase inhibitors (TKIs) have greatly improved the treatment outcome for most patients with chronic myeloid leukemia (CML). Ponatinib is a new pan-inhibitor of TK active in resistant CML. This study aimed to evaluate the efficacy and safety of ponatinib in patients suffering from CML. Patients and methods: This multicenter, non-randomized, observational, retrospective study evaluated the efficacy and safety of ponatinib administered in adult CML patients in any disease phase, including those with a detected ABL T315I mutation, which were resistant or intolerant to previous-generation TKIs. The study comprised 43 patients benefiting from the ponatinib donation program who were treated in 16 Polish centers. Results: For patients who started treatment with ponatinib in chronic phase (CP) (n = 23) and in accelerated phase (AP) (n = 3) the median time on ponatinib was 19.5 months (range: 1.0-35.4), and 31.7 months (range: 31.0-34.1), respectively. All these patients were in CP after 1 month of treatment and at the end of observation - none of them progressed to AP or blastic phase (BP) during the study, meaning that progression-free survival was 100% at the end of observation (35.4 months). The estimated 2-year survival in this group of patients was 84%. For all 43 patients, median survival was not reached (lower quartile 6.3 months), and estimated 2-year survival was 60%. Conclusion: Our analysis confirmed ponatinib efficacy in a significant proportion of patients heavily pre-treated with TKIs achieving durable responses in both CP and AP/BP CML groups.
      原文链接:
    • NSTL
    • Cig Media Group, Lp

    ?FLT3-ITD Mutation Does Not Influence Survival Outcome in Adult Acute Promyelocytic Leukemia Patients Treated With ATO and ATRA-Based Therapeutic Regimen: Experience From a North Indian Tertiary Care Centre?

    Deka, Riju RaniNaseem, ShanoBhatia, PrateekBinota, Jogeshwar...
    8页
    查看更多>>摘要：FLT3-ITD was frequent in adult acute promyelocytic leukemia cases although its presence did not influence the treatment outcome in an arsenic trioxide (ATO) and all-trans-retinoic acid (ATRA) based therapeutic regimen. However, its presence was associated with predictors of inferior survival outcome like leukocytosis and BCR3 transcript type. Introduction: NPM1 and FLT3 -ITD are frequently mutated genes in acute myeloid leukemia. We studied clinicohematological profile and survival outcome of adult acute promyelocytic leukemia (APL) patients harboring these mutations. Materials and Methods: De novo APL cases ( > 12 years), enrolled between January 2019 and June 2020, were evaluated for FLT3 -ITD and NPM1 mutations (A, B, D mutations) by conventional and real-time qualitative PCR respectively. Results: FLT3 -ITD mutation was detected in 12 of 36 (33.3%) de novo APLs cases while NPM1 mutation was not detected. FLT3 -ITD was more frequently associated with Sanz high-risk category as compared to the intermediate-risk category (75% vs. 29%, P = .02), with BCR3 transcript type ( P = .08) and higher median WBC count [22.7 ?? 10 9 /L)(range 1.3-184), P = .018]. One and half-years overall survival (OS) and event-free survival (EFS) were not significantly altered by the presence/absence of FLT3 -ITD mutation (OS 86% vs. 70%, P = .32; EFS 86% vs. 70%, P = .33), between genders (OS, EFS both 89% in males vs. 69% in females, P = .15) and between adolescent and younger adults (AYA) ( ??? 30 years) and older adult APL cases ( > 30 years) (OS 86% vs. 78%, P = .55; EFS 85% vs. 77%, P = .55), however were significantly lower with BCR3 transcript as compared to BCR1 transcript (OS 56% vs. 91%, P = .019; EFS 56% vs. 91%, P = .016) in univariate analysis, although not in multivariate analysis. One and half-year OS and EFS was 57% (6/14, P = .009 for each) in high-risk APL. Conclusion: FLT3 -ITD mutation did not influence survival outcome in adult APL treated with ATO and ATRA-based therapeutic regimen.
      原文链接:
    • NSTL
    • Cig Media Group, Lp

    P-207: A multi-center, phase 1b study to assess the safety, Pharmacokinetics and efficacy of subcutaneous Isatuximab plus Pomalidomide and Dexamethasone, in patients with Relapsed/Refractory Multiple Myeloma [vol 21, Pg S152, 2021)

    Moreau, PhilippeParmar, GurdeepPrince, MilesOcio, Enrique M....
    1页
      原文链接:
    • NSTL
    • Cig Media Group, Lp

    "OAB-005: Update of safety and efficacy of Isatuximab short-duration fixed-volume infusion plus Bortezomib, Lenalidomide, and Dexamethasone combined therapy for NDMM ineligible/with no immediate intent for ASCT" [vol 21, pg S3, 2021]

    Moreau, PhilippeOcio, Enrique M.Perrot, AuroreBories, Pierre...
    1页
      原文链接:
    • NSTL
    • Cig Media Group, Lp