Pub Date : 2024-11-07DOI: 10.1016/j.clml.2024.11.003
Fadi G Haddad, Koji Sasaki, Jayastu Senapati, Shimin Hu, Sara Dellasala, Ghayas C Issa, Elias Jabbour, Hagop Kantarjian
Introduction: The discontinuation of third-generation BCR::ABL1 tyrosine kinase inhibitors (TKIs) in patients with chronic myeloid leukemia in chronic phase (CML-CP) is not well understood. We aim to evaluate treatment-free remission in patients with CML-CP who discontinue ponatinib.
Methods: We retrospectively reviewed 361 patients who attempted TKI discontinuation between November 2005 and February 2024 and identified those receiving ponatinib at the time of discontinuation. Molecular relapse-free survival (MRFS) was calculated from the time of ponatinib discontinuation to the date of loss of major molecular response (MMR) or last follow-up.
Results: Eleven patients discontinued ponatinib. Before ponatinib discontinuation, patients were on TKI therapy for a median of 146.6 months and on ponatinib for a median of 67.5 months. The median number of TKIs prior to starting ponatinib was 2 (range, 1-3). The median durations of sustained MR4 and MR4.5 before ponatinib discontinuation were 32.8 and 29.4 months, respectively. After a median follow-up of 60.3 months, the 60-month MRFS rate was 53%. Five patients lost MMR; their median MR4.5 duration was 5 months before ponatinib discontinuation.
Conclusion: Ponatinib discontinuation is feasible in patients with CML-CP failing prior TKIs. Patients who achieve sustained MR4.5 for at least 2 years have the highest likelihood of remaining in treatment-free remission following ponatinib discontinuation.
{"title":"Successful Treatment-Free Remission After Ponatinib Discontinuation in Pretreated Patients with Chronic Myeloid Leukemia in Chronic Phase.","authors":"Fadi G Haddad, Koji Sasaki, Jayastu Senapati, Shimin Hu, Sara Dellasala, Ghayas C Issa, Elias Jabbour, Hagop Kantarjian","doi":"10.1016/j.clml.2024.11.003","DOIUrl":"10.1016/j.clml.2024.11.003","url":null,"abstract":"<p><strong>Introduction: </strong>The discontinuation of third-generation BCR::ABL1 tyrosine kinase inhibitors (TKIs) in patients with chronic myeloid leukemia in chronic phase (CML-CP) is not well understood. We aim to evaluate treatment-free remission in patients with CML-CP who discontinue ponatinib.</p><p><strong>Methods: </strong>We retrospectively reviewed 361 patients who attempted TKI discontinuation between November 2005 and February 2024 and identified those receiving ponatinib at the time of discontinuation. Molecular relapse-free survival (MRFS) was calculated from the time of ponatinib discontinuation to the date of loss of major molecular response (MMR) or last follow-up.</p><p><strong>Results: </strong>Eleven patients discontinued ponatinib. Before ponatinib discontinuation, patients were on TKI therapy for a median of 146.6 months and on ponatinib for a median of 67.5 months. The median number of TKIs prior to starting ponatinib was 2 (range, 1-3). The median durations of sustained MR4 and MR4.5 before ponatinib discontinuation were 32.8 and 29.4 months, respectively. After a median follow-up of 60.3 months, the 60-month MRFS rate was 53%. Five patients lost MMR; their median MR4.5 duration was 5 months before ponatinib discontinuation.</p><p><strong>Conclusion: </strong>Ponatinib discontinuation is feasible in patients with CML-CP failing prior TKIs. Patients who achieve sustained MR4.5 for at least 2 years have the highest likelihood of remaining in treatment-free remission following ponatinib discontinuation.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142726569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-07DOI: 10.1016/j.clml.2024.11.005
Varun Iyengar, Paul Hamlin, Pallawi Torka
Older adults (OA) with DLBCL are a heterogenous population with suboptimal outcomes. In this review, we identify and address the unique challenges encountered in the care of OA with DLBCL. We elaborate on the role and limitations of current geriatric assessment (GA) tools and ways to incorporate fitness in therapeutic decision making. We suggest best practices to implement GA in routine practice and clinical trials. The most widely used tool is simplified GA (sGA) which categorizes patients into fit, unfit and frail groups. Patients who are fit benefit from full dose/curative approach, whereas consideration should be made to reduce the intensity of chemotherapy for unfit patients. Frail patients with DLBCL are a major unmet need without any satisfactory treatment options. Ongoing investigations combining novel therapies into chemotherapy-free regimens are underway with promising early results. In the relapsed/refractory (R/R) setting, anti-CD19 CAR-T cell therapy (CART) is now the standard of care for primary refractory disease or relapse within 12 months of completing therapy. Autologous stem cell transplant is still a consideration for fit OA with relapse >12 months after completing therapy. The recent approval of bispecific antibodies is a welcome advance that will greatly benefit OA not eligible for CART. Other regimens available for patients ineligible for CART or for those who experience progression post-CART include polatuzumab-rituximab±bendamustine, tafasitamab-lenalidomide, loncastuximab or chemotherapy-based approaches such as rituximab-gemcitabine-oxaliplatin. We discuss the changing paradigm in R/R DLBCL and spotlight emerging data from recent congresses that can improve outcomes in this vulnerable population.
{"title":"SOHO State of the Art Updates and Next Questions | Diffuse Large B-Cell Lymphoma in Older Adults: A Comprehensive Review.","authors":"Varun Iyengar, Paul Hamlin, Pallawi Torka","doi":"10.1016/j.clml.2024.11.005","DOIUrl":"https://doi.org/10.1016/j.clml.2024.11.005","url":null,"abstract":"<p><p>Older adults (OA) with DLBCL are a heterogenous population with suboptimal outcomes. In this review, we identify and address the unique challenges encountered in the care of OA with DLBCL. We elaborate on the role and limitations of current geriatric assessment (GA) tools and ways to incorporate fitness in therapeutic decision making. We suggest best practices to implement GA in routine practice and clinical trials. The most widely used tool is simplified GA (sGA) which categorizes patients into fit, unfit and frail groups. Patients who are fit benefit from full dose/curative approach, whereas consideration should be made to reduce the intensity of chemotherapy for unfit patients. Frail patients with DLBCL are a major unmet need without any satisfactory treatment options. Ongoing investigations combining novel therapies into chemotherapy-free regimens are underway with promising early results. In the relapsed/refractory (R/R) setting, anti-CD19 CAR-T cell therapy (CART) is now the standard of care for primary refractory disease or relapse within 12 months of completing therapy. Autologous stem cell transplant is still a consideration for fit OA with relapse >12 months after completing therapy. The recent approval of bispecific antibodies is a welcome advance that will greatly benefit OA not eligible for CART. Other regimens available for patients ineligible for CART or for those who experience progression post-CART include polatuzumab-rituximab±bendamustine, tafasitamab-lenalidomide, loncastuximab or chemotherapy-based approaches such as rituximab-gemcitabine-oxaliplatin. We discuss the changing paradigm in R/R DLBCL and spotlight emerging data from recent congresses that can improve outcomes in this vulnerable population.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Detecting anthracyclines-induced cardiotoxicity before the onset of left ventricular dysfunction could enable the timely initiation of cardioprotective measures. 2D-Echocardiography (ECHO) with global longitudinal strain (GLS) and cardiac biomarkers are valuable for the early prediction of cardiotoxicity.
Objectives
We aimed to evaluate the predictive utility of 2D-ECHO-GLS and cardiac biomarkers exclusively in patients with lymphoma treated with a doxorubicin-based regimen.
Methods
The study included lymphoma patients ≥14 years of age of either sex who were planned for a doxorubicin-based regimen. All eligible patients underwent 2D-ECHO-GLS and cardiac biomarkers (troponin T and pro-brain natriuretic peptide) measurements at the baseline (V1), after 3rd chemotherapy cycle (V2), and after treatment completion (V3). Incidence, risk factors, and early predictors for cardiotoxicity were assessed using SPSS software version 25. The study was registered with CTRI (CTRI/2021/07/034518).
Results
40 patients (median age, 42 years) had evaluations available at all 3 time points. Three out of 40 (7.5%) patients developed cardiotoxicity at V3. Patients with cardiotoxicity had a significantly higher mean age (P = .045) and a greater incidence of hypertension (P = .012) than those without cardiotoxicity. At V2, the mean GLS threshold (-18.1%) and Δ GLS threshold ≥15% from baseline were significant early predictors of subsequent cardiotoxicity. Despite an exponential rise from V1 to V3, the cardiac biomarkers failed to predict cardiotoxicity.
Conclusions
Patients with lymphoma treated with doxorubicin-based regimens have a significant risk of developing cardiac dysfunction. A greater than 15% fall in GLS from baseline after 3rd chemotherapy cycle could predict subsequent cardiotoxicity.
{"title":"Incidence, Risk Factors and Early Prediction of Doxorubicin-Induced Cardiotoxicity by Global Longitudinal Strain and Cardiac Biomarkers in Indian Patients With Lymphoma: A Prospective Observational Study","authors":"Lucky kumar , Rajesh Vijayvergiya , Ankur Jain , Charanpreet Singh , Arihant Jain , Gaurav Prakash , Alka Khadwal , Pankaj Malhotra","doi":"10.1016/j.clml.2024.10.008","DOIUrl":"10.1016/j.clml.2024.10.008","url":null,"abstract":"<div><h3>Background</h3><div>Detecting anthracyclines-induced cardiotoxicity before the onset of left ventricular dysfunction could enable the timely initiation of cardioprotective measures. 2D-Echocardiography (ECHO) with global longitudinal strain (GLS) and cardiac biomarkers are valuable for the early prediction of cardiotoxicity.</div></div><div><h3>Objectives</h3><div>We aimed to evaluate the predictive utility of 2D-ECHO-GLS and cardiac biomarkers exclusively in patients with lymphoma treated with a doxorubicin-based regimen.</div></div><div><h3>Methods</h3><div>The study included lymphoma patients ≥14 years of age of either sex who were planned for a doxorubicin-based regimen. All eligible patients underwent 2D-ECHO-GLS and cardiac biomarkers (troponin T and pro-brain natriuretic peptide) measurements at the baseline (V1), after 3<sup>rd</sup> chemotherapy cycle (V2), and after treatment completion (V3). Incidence, risk factors, and early predictors for cardiotoxicity were assessed using SPSS software version 25. The study was registered with CTRI (CTRI/2021/07/034518).</div></div><div><h3>Results</h3><div>40 patients (median age, 42 years) had evaluations available at all 3 time points. Three out of 40 (7.5%) patients developed cardiotoxicity at V3. Patients with cardiotoxicity had a significantly higher mean age (<em>P</em> = .045) and a greater incidence of hypertension (<em>P</em> = .012) than those without cardiotoxicity. At V2, the mean GLS threshold (-18.1%) and Δ GLS threshold ≥15% from baseline were significant early predictors of subsequent cardiotoxicity. Despite an exponential rise from V1 to V3, the cardiac biomarkers failed to predict cardiotoxicity.</div></div><div><h3>Conclusions</h3><div>Patients with lymphoma treated with doxorubicin-based regimens have a significant risk of developing cardiac dysfunction. A greater than 15% fall in GLS from baseline after 3<sup>rd</sup> chemotherapy cycle could predict subsequent cardiotoxicity.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"25 3","pages":"Pages e143-e150"},"PeriodicalIF":2.7,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-24DOI: 10.1016/j.clml.2024.10.013
Loïc Ysebaert , Stéphane Ederhy , Véronique Leblond , Stéphanie Malartre , Anaïs Portalier , Vincent Sibaud , Cécile Tomowiak , Jérémie Zerbit , Delphi Acalabrutinib Safety Study Group
Acalabrutinib, a second-generation Bruton's tyrosine kinase inhibitor (BTKi), offers an improved safety profile compared to first-generation inhibitors like ibrutinib. While BTKi guidelines exist, practical differences between BTKis—such as drug interactions and tolerance—are not fully addressed. Therefore, a consensus on acalabrutinib use would benefit the medical community. This 2-round Delphi study involved hematologists, pharmacists, cardiologists, dermatologists, and nurse practitioners throughout France to establish consensus-based practical guidance on managing adverse events (AEs) associated with acalabrutinib in chronic lymphocytic leukemia. Key findings highlighted the need for a hospital pharmacist to analyze drug interactions before starting acalabrutinib. Additionally, the experts’ opinion was to avoid the concomitant use of acalabrutinib with strong CYP3A inhibitors due to an increased risk of toxicity and with strong CYP3A inducers due to potential efficacy concerns. Importantly, our study did not find contraindications for acalabrutinib in patients with current or previous atrial fibrillation. The panel emphasized the importance of measuring blood pressure at every clinical visit for patients treated with acalabrutinib and opposed the initiation of acalabrutinib in patients on both aspirin and clopidogrel. For invasive dermatological or dental procedures, acalabrutinib should be discontinued 4 days prior and resumed 48 hours postprocedure in the absence of bleeding. Additionally, patients should be informed about the risk of headaches, particularly during the first month of treatment, and paracetamol use in combination with caffeine is recommended for managing grade ≥ 2 headaches under acalabrutinib treatment. This Delphi study underscored the effectiveness of a collaborative process in enhancing the management of acalabrutinib-associated AEs.
{"title":"Expert Opinion on Managing Adverse Reactions Associated With Acalabrutinib Therapy: A Delphi Consensus From France","authors":"Loïc Ysebaert , Stéphane Ederhy , Véronique Leblond , Stéphanie Malartre , Anaïs Portalier , Vincent Sibaud , Cécile Tomowiak , Jérémie Zerbit , Delphi Acalabrutinib Safety Study Group","doi":"10.1016/j.clml.2024.10.013","DOIUrl":"10.1016/j.clml.2024.10.013","url":null,"abstract":"<div><div>Acalabrutinib, a second-generation Bruton's tyrosine kinase inhibitor (BTKi), offers an improved safety profile compared to first-generation inhibitors like ibrutinib. While BTKi guidelines exist, practical differences between BTKis—such as drug interactions and tolerance—are not fully addressed. Therefore, a consensus on acalabrutinib use would benefit the medical community. This 2-round Delphi study involved hematologists, pharmacists, cardiologists, dermatologists, and nurse practitioners throughout France to establish consensus-based practical guidance on managing adverse events (AEs) associated with acalabrutinib in chronic lymphocytic leukemia. Key findings highlighted the need for a hospital pharmacist to analyze drug interactions before starting acalabrutinib. Additionally, the experts’ opinion was to avoid the concomitant use of acalabrutinib with strong CYP3A inhibitors due to an increased risk of toxicity and with strong CYP3A inducers due to potential efficacy concerns. Importantly, our study did not find contraindications for acalabrutinib in patients with current or previous atrial fibrillation. The panel emphasized the importance of measuring blood pressure at every clinical visit for patients treated with acalabrutinib and opposed the initiation of acalabrutinib in patients on both aspirin and clopidogrel. For invasive dermatological or dental procedures, acalabrutinib should be discontinued 4 days prior and resumed 48 hours postprocedure in the absence of bleeding. Additionally, patients should be informed about the risk of headaches, particularly during the first month of treatment, and paracetamol use in combination with caffeine is recommended for managing grade ≥ 2 headaches under acalabrutinib treatment. This Delphi study underscored the effectiveness of a collaborative process in enhancing the management of acalabrutinib-associated AEs.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"25 3","pages":"Pages e173-e181"},"PeriodicalIF":2.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-23DOI: 10.1016/j.clml.2024.10.012
Sahar Khan , Debra J. Bergstrom , Julie Côté , Rami Kotb , Richard LeBlanc , Martha L. Louzada , Hira S. Mian , Ibraheem Othman , Gabriele Colasurdo , Alissa Visram
The availability of effective therapies for multiple myeloma (MM) has sparked debate on the role of first line autologous stem cell transplantation (ASCT), particularly in standard-risk patients. However, treatment for individuals with high-risk disease continues to display suboptimal outcomes. With novel therapies used earlier, practice is changing rapidly in the field of MM. Presently, quadruplet induction therapy incorporating an anti-CD38 monoclonal antibody to a proteasome inhibitor and an immunomodulatory drug prior to ASCT followed by maintenance therapy stands as the foremost strategy for attaining deep and sustained responses in transplant eligible MM (TEMM).
This Canadian Consensus Guideline Consortium (CGC) proposes consensus recommendations for the first line treatment of TEMM. To address the needs of physicians and people diagnosed with MM, this document focuses on ASCT eligibility, induction therapy, mobilization and collection, conditioning, consolidation, and maintenance therapy, as well as, high-risk populations, management of adverse events, assessment of treatment response, and monitoring for disease relapse. The CGC will periodically review the recommendations herein and update as necessary.
{"title":"First Line Treatment of Newly Diagnosed Transplant Eligible Multiple Myeloma Recommendations From a Canadian Consensus Guideline Consortium","authors":"Sahar Khan , Debra J. Bergstrom , Julie Côté , Rami Kotb , Richard LeBlanc , Martha L. Louzada , Hira S. Mian , Ibraheem Othman , Gabriele Colasurdo , Alissa Visram","doi":"10.1016/j.clml.2024.10.012","DOIUrl":"10.1016/j.clml.2024.10.012","url":null,"abstract":"<div><div>The availability of effective therapies for multiple myeloma (MM) has sparked debate on the role of first line autologous stem cell transplantation (ASCT), particularly in standard-risk patients. However, treatment for individuals with high-risk disease continues to display suboptimal outcomes. With novel therapies used earlier, practice is changing rapidly in the field of MM. Presently, quadruplet induction therapy incorporating an anti-CD38 monoclonal antibody to a proteasome inhibitor and an immunomodulatory drug prior to ASCT followed by maintenance therapy stands as the foremost strategy for attaining deep and sustained responses in transplant eligible MM (TEMM).</div><div>This Canadian Consensus Guideline Consortium (CGC) proposes consensus recommendations for the first line treatment of TEMM. To address the needs of physicians and people diagnosed with MM, this document focuses on ASCT eligibility, induction therapy, mobilization and collection, conditioning, consolidation, and maintenance therapy, as well as, high-risk populations, management of adverse events, assessment of treatment response, and monitoring for disease relapse. The CGC will periodically review the recommendations herein and update as necessary.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"25 3","pages":"Pages e151-e172"},"PeriodicalIF":2.7,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-16DOI: 10.1016/j.clml.2024.10.001
Claire N. Harrison , Ruben Mesa , Moshe Talpaz , Vikas Gupta , Aaron T. Gerds , Andrew Perkins , Yeow Tee Goh , Maria Laura Fox , Donal McLornan , Jeanne Palmer , Lynda Foltz , Alessandro Vannucchi , Steffen Koschmieder , Francesco Passamonti , Sung-Eun Lee , Catherine Ellis , Bryan Strouse , Francisco J. Gonzalez Carreras , Stephen T. Oh
Purpose
Anemia is a cardinal feature of myelofibrosis often managed with red blood cell (RBC) transfusions, which may contribute to negative prognostic, quality-of-life, and healthcare-related economic impacts. The Janus kinase (JAK) 1/JAK2/activin A receptor type 1 inhibitor momelotinib was approved for the treatment of patients with myelofibrosis and anemia based on clinical trial evidence of anemia, spleen, and symptom benefits illustrated using binomial response/nonresponse endpoints. In the present post hoc, descriptive analyses, the impact of momelotinib on RBC transfusion burden over time was further characterized across JAK inhibitor–naive and –experienced patients.
Methods
All RBC units transfused were collected during the baseline and 24-week treatment periods, initially in a single-arm phase 2 study as proof-of-concept analysis, and then versus comparators (ruxolitinib, best available therapy [BAT], and danazol) in the phase 3 SIMPLIFY-1, SIMPLIFY-2, and MOMENTUM studies, respectively.
Results
In the phase 2 study, mean transfusion requirement changed by −1.5 units/28 days, with 85% of patients (35/41) achieving numeric transfusion reduction. Across SIMPLIFY-1, SIMPLIFY-2, and MOMENTUM, mean transfusion requirements decreased with momelotinib (−0.1, −0.36, and −0.86 units/28 days), while mean requirements with ruxolitinib, BAT, and danazol changed by +0.39, 0, and ‒0.28 units/28 days, respectively. Overall, 87% (185/213), 77% (79/103), and 85% (110/130) of patients had improved or stable transfusion intensities with momelotinib versus 54% (117/216), 62% (32/52), and 63% (41/65) with ruxolitinib, BAT, and danazol.
Conclusion
These novel time-dependent transfusion burden analyses demonstrate that momelotinib is associated with anemia-related benefits in most patients and greater transfusion burden reduction versus comparators.
{"title":"Longitudinal Assessment of Transfusion Intensity in Patients With JAK Inhibitor–Naive or –Experienced Myelofibrosis Treated With Momelotinib","authors":"Claire N. Harrison , Ruben Mesa , Moshe Talpaz , Vikas Gupta , Aaron T. Gerds , Andrew Perkins , Yeow Tee Goh , Maria Laura Fox , Donal McLornan , Jeanne Palmer , Lynda Foltz , Alessandro Vannucchi , Steffen Koschmieder , Francesco Passamonti , Sung-Eun Lee , Catherine Ellis , Bryan Strouse , Francisco J. Gonzalez Carreras , Stephen T. Oh","doi":"10.1016/j.clml.2024.10.001","DOIUrl":"10.1016/j.clml.2024.10.001","url":null,"abstract":"<div><h3>Purpose</h3><div>Anemia is a cardinal feature of myelofibrosis often managed with red blood cell (RBC) transfusions, which may contribute to negative prognostic, quality-of-life, and healthcare-related economic impacts. The Janus kinase (JAK) 1/JAK2/activin A receptor type 1 inhibitor momelotinib was approved for the treatment of patients with myelofibrosis and anemia based on clinical trial evidence of anemia, spleen, and symptom benefits illustrated using binomial response/nonresponse endpoints. In the present post hoc, descriptive analyses, the impact of momelotinib on RBC transfusion burden over time was further characterized across JAK inhibitor–naive and –experienced patients.</div></div><div><h3>Methods</h3><div>All RBC units transfused were collected during the baseline and 24-week treatment periods, initially in a single-arm phase 2 study as proof-of-concept analysis, and then versus comparators (ruxolitinib, best available therapy [BAT], and danazol) in the phase 3 SIMPLIFY-1, SIMPLIFY-2, and MOMENTUM studies, respectively.</div></div><div><h3>Results</h3><div>In the phase 2 study, mean transfusion requirement changed by −1.5 units/28 days, with 85% of patients (35/41) achieving numeric transfusion reduction. Across SIMPLIFY-1, SIMPLIFY-2, and MOMENTUM, mean transfusion requirements decreased with momelotinib (−0.1, −0.36, and −0.86 units/28 days), while mean requirements with ruxolitinib, BAT, and danazol changed by +0.39, 0, and ‒0.28 units/28 days, respectively. Overall, 87% (185/213), 77% (79/103), and 85% (110/130) of patients had improved or stable transfusion intensities with momelotinib versus 54% (117/216), 62% (32/52), and 63% (41/65) with ruxolitinib, BAT, and danazol.</div></div><div><h3>Conclusion</h3><div>These novel time-dependent transfusion burden analyses demonstrate that momelotinib is associated with anemia-related benefits in most patients and greater transfusion burden reduction versus comparators.</div></div><div><h3>Trial registration</h3><div>ClinicalTrials.gov identifiers: NCT02515630, NCT01969838, NCT02101268, NCT04173494.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"25 3","pages":"Pages 199-211"},"PeriodicalIF":2.7,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-16DOI: 10.1016/j.clml.2024.10.009
Jonathan M Weiss, Tycel J Phillips
MCL remains incurable, and patients who relapse post BTK inhibitors have poor outcomes. BsAbs and CAR T cell therapy are novel strategies to treat patients with R/R MCL. These therapies exhibit favorable outcomes and side effect profiles in a previously dismal space. This review looks to detail the current data available for BsAbs and CAR T cell therapy in R/R MCL, and how are current treatment paradigm is shifting to incorporate these novel agents.
{"title":"SOHO State of the Art Updates and Next Questions | The Current State of CAR T-Cell Therapy and Bispecific Antibodies in Mantle Cell Lymphoma.","authors":"Jonathan M Weiss, Tycel J Phillips","doi":"10.1016/j.clml.2024.10.009","DOIUrl":"https://doi.org/10.1016/j.clml.2024.10.009","url":null,"abstract":"<p><p>MCL remains incurable, and patients who relapse post BTK inhibitors have poor outcomes. BsAbs and CAR T cell therapy are novel strategies to treat patients with R/R MCL. These therapies exhibit favorable outcomes and side effect profiles in a previously dismal space. This review looks to detail the current data available for BsAbs and CAR T cell therapy in R/R MCL, and how are current treatment paradigm is shifting to incorporate these novel agents.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-11DOI: 10.1016/j.clml.2024.10.005
Frida Bugge Askeland , Hege M. Frøen , Nils Bolstad , Per Medbøe Thorsby , Fredrik Schjesvold , Anne Cathrine Parelius Wammer , Ivar Følling , Geir E. Tjønnfjord
Background
Monoclonal insulin autoimmune syndrome (IAS) is a very rare disease characterized by severe attacks of hypoglycemia caused by circulating anti-insulin antibodies produced by a B-cell clone, usually clonal plasma cells.
Method
We present 2 female Norwegian patients with monoclonal IAS. The anti-insulin antibodies were quantified by immune precipitation and characterized using a 3-step manual in-house assay. Both patients received plasma cell directed therapy.
Result
The first patient received plasma cell directed therapy for a time-limited period and achieved a sustained clinical remission without detectable anti-insulin antibodies. The second patient receives continuous plasma cell directed therapy and is in clinical remission with low values of detectable anti-insulin antibodies.
Conclusion
Plasma cell directed therapy was effective and safe in our 2 cases of monoclonal IAS. We recommend considering plasma cell directed therapy for these patients.
{"title":"Monoclonal Insulin Autoimmune Syndrome Successfully Treated With Plasma Cell Directed Therapy","authors":"Frida Bugge Askeland , Hege M. Frøen , Nils Bolstad , Per Medbøe Thorsby , Fredrik Schjesvold , Anne Cathrine Parelius Wammer , Ivar Følling , Geir E. Tjønnfjord","doi":"10.1016/j.clml.2024.10.005","DOIUrl":"10.1016/j.clml.2024.10.005","url":null,"abstract":"<div><h3>Background</h3><div>Monoclonal insulin autoimmune syndrome (IAS) is a very rare disease characterized by severe attacks of hypoglycemia caused by circulating anti-insulin antibodies produced by a B-cell clone, usually clonal plasma cells.</div></div><div><h3>Method</h3><div>We present 2 female Norwegian patients with monoclonal IAS. The anti-insulin antibodies were quantified by immune precipitation and characterized using a 3-step manual in-house assay. Both patients received plasma cell directed therapy.</div></div><div><h3>Result</h3><div>The first patient received plasma cell directed therapy for a time-limited period and achieved a sustained clinical remission without detectable anti-insulin antibodies. The second patient receives continuous plasma cell directed therapy and is in clinical remission with low values of detectable anti-insulin antibodies.</div></div><div><h3>Conclusion</h3><div>Plasma cell directed therapy was effective and safe in our 2 cases of monoclonal IAS. We recommend considering plasma cell directed therapy for these patients.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"25 3","pages":"Pages e127-e130"},"PeriodicalIF":2.7,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-10DOI: 10.1016/j.clml.2024.10.007
Antonella Poloni , Klas Raaschou-Jensen , Francisca Hernandez Mohedo , Stefania Paolini , Esther Natalie Oliva , Francesco Buccisano , Alberto Vasconcelos , Iris Kim , Aidan Makwana , David Bernasconi , Barbara Rosettani , Thomas Prebet , Valeria Santini
Background
This noninterventional postauthorization safety study assessed the safety and effectiveness of lenalidomide in patients with transfusion-dependent, International Prognostic Scoring System (IPSS) Low- or Intermediate (Int)-1-risk myelodysplastic syndromes (MDS) associated with isolated deletion of 5q (del[5q]) who were treated in routine care.
Patients and Methods
Eligible adult patients in the lenalidomide cohort had transfusion-dependent, IPSS Low- or Int-1-risk MDS and isolated del(5q) and had received ≥ 1 dose of lenalidomide between 2014 and 2022. The primary endpoint was the 24-month cumulative incidence of acute myeloid leukemia (AML) progression. Overall survival (OS) was estimated by Kaplan–Meier analysis and safety data were collected.
Results
In total, 296 patients received ≥ 1 dose of lenalidomide (lenalidomide cohort, safety population) and 277 had received ≥ 1 complete cycle of lenalidomide (primary population). In the safety population, 44.3% of patients completed 3-year follow-up and 55.1% discontinued, with 33.1% discontinuing due to death. In the primary population, 24-month cumulative incidence of AML progression was 12.7% (95% confidence interval, 8.9%-17.1%) and estimated OS probability was 78.3% at 24 months and 63.9% at 36 months. Grade 3/4 treatment-emergent adverse events were experienced by 67.2% of the safety population, and these led to discontinuation in 35.5% of patients. There were no new safety signals.
Conclusion
These real-world data support the established benefit-risk profile of lenalidomide in transfusion-dependent IPSS Low- or Int-1-risk MDS with isolated del(5q).
{"title":"Lenalidomide in Transfusion-Dependent IPSS Low- or Intermediate-1-Risk Myelodysplastic Syndromes and Isolated Del(5q): Results of a European Postauthorization Safety Surveillance Study","authors":"Antonella Poloni , Klas Raaschou-Jensen , Francisca Hernandez Mohedo , Stefania Paolini , Esther Natalie Oliva , Francesco Buccisano , Alberto Vasconcelos , Iris Kim , Aidan Makwana , David Bernasconi , Barbara Rosettani , Thomas Prebet , Valeria Santini","doi":"10.1016/j.clml.2024.10.007","DOIUrl":"10.1016/j.clml.2024.10.007","url":null,"abstract":"<div><h3>Background</h3><div>This noninterventional postauthorization safety study assessed the safety and effectiveness of lenalidomide in patients with transfusion-dependent, International Prognostic Scoring System (IPSS) Low- or Intermediate (Int)-1-risk myelodysplastic syndromes (MDS) associated with isolated deletion of 5q (del[5q]) who were treated in routine care.</div></div><div><h3>Patients and Methods</h3><div>Eligible adult patients in the lenalidomide cohort had transfusion-dependent, IPSS Low- or Int-1-risk MDS and isolated del(5q) and had received ≥ 1 dose of lenalidomide between 2014 and 2022. The primary endpoint was the 24-month cumulative incidence of acute myeloid leukemia (AML) progression. Overall survival (OS) was estimated by Kaplan–Meier analysis and safety data were collected.</div></div><div><h3>Results</h3><div>In total, 296 patients received ≥ 1 dose of lenalidomide (lenalidomide cohort, safety population) and 277 had received ≥ 1 complete cycle of lenalidomide (primary population). In the safety population, 44.3% of patients completed 3-year follow-up and 55.1% discontinued, with 33.1% discontinuing due to death. In the primary population, 24-month cumulative incidence of AML progression was 12.7% (95% confidence interval, 8.9%-17.1%) and estimated OS probability was 78.3% at 24 months and 63.9% at 36 months. Grade 3/4 treatment-emergent adverse events were experienced by 67.2% of the safety population, and these led to discontinuation in 35.5% of patients. There were no new safety signals.</div></div><div><h3>Conclusion</h3><div>These real-world data support the established benefit-risk profile of lenalidomide in transfusion-dependent IPSS Low- or Int-1-risk MDS with isolated del(5q).</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"25 3","pages":"Pages e131-e142"},"PeriodicalIF":2.7,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-09DOI: 10.1016/j.clml.2024.09.014
Julie E. Chang , Danielle McQuinn , Meredith Hyun , KyungMann Kim , Vaishalee P. Kenkre , Saurabh A. Rajguru , Priyanka A. Pophali , Mariah Endres , Mitch Howard , Tim Wassenaar , Ruth Callaway Warren , Ryan J. Mattison , Kari B. Wisinski , Christopher D. Fletcher
Introduction
Obinutuzumab is hypothesized to improve progression-free survival (PFS) combined with bendamustine induction in mantle cell lymphoma (MCL). Measurable-residual disease (MRD) testing may predict benefit from maintenance therapy.
Methods
Adults (≥ 18 years) with untreated MCL ineligible for intensive therapies received 4 to 6 cycles of bendamustine + obinutuzumab (BO) followed by consolidation obinutuzumab (CO). Restaging after CO included MRD assessment by next-generation sequencing of bone marrow aspirate (BMA) and peripheral blood (PB). Maintenance obinutuzumab (MO) was omitted for patients with imaging complete response (CR) and MRD-negativity in PB/BMA. All other patients received 8 cycles MO. Primary endpoint is PFS; secondary endpoints are response rates, overall survival, and estimation of MRD status.
Results
Twenty-one patients enrolled, with median age 70 years and stage IV disease in 95%. Twenty patients completed BO; 10 patients received MO per protocol. Six patients did not complete MO due to progression (n = 4), infection (n = 1) and carcinoma (n = 1). Overall response is 95% (75% CR, 20% partial response). Concordance rate between post-consolidation MRD testing in PB and BMA was 70%.
After a median follow-up of 43.9 months, median PFS is 46.5 months. The observed difference between 2-year PFS in groups receiving MO versus observation was not statistically significant (HR 0.45, 95% CI, 0.10-1.91). Most common grade 3/4 toxicities were neutropenia, leukopenia, and infections.
Conclusions
BO is a tolerable induction regimen with higher rates of CR compared with historical rates with bendamustine + rituximab. Omission of MO did not worsen outcomes in patients achieving MRD-negative status after nonintensive induction/consolidation therapy.
{"title":"Measurable Residual Disease Testing Following Nonintensive Chemoimmunotherapy is Predictive of Need for Maintenance Therapy in Previously Untreated Mantle Cell Lymphoma: A Wisconsin Oncology Network Study","authors":"Julie E. Chang , Danielle McQuinn , Meredith Hyun , KyungMann Kim , Vaishalee P. Kenkre , Saurabh A. Rajguru , Priyanka A. Pophali , Mariah Endres , Mitch Howard , Tim Wassenaar , Ruth Callaway Warren , Ryan J. Mattison , Kari B. Wisinski , Christopher D. Fletcher","doi":"10.1016/j.clml.2024.09.014","DOIUrl":"10.1016/j.clml.2024.09.014","url":null,"abstract":"<div><h3>Introduction</h3><div>Obinutuzumab is hypothesized to improve progression-free survival (PFS) combined with bendamustine induction in mantle cell lymphoma (MCL). Measurable-residual disease (MRD) testing may predict benefit from maintenance therapy.</div></div><div><h3>Methods</h3><div>Adults (≥ 18 years) with untreated MCL ineligible for intensive therapies received 4 to 6 cycles of bendamustine + obinutuzumab (BO) followed by consolidation obinutuzumab (CO). Restaging after CO included MRD assessment by next-generation sequencing of bone marrow aspirate (BMA) and peripheral blood (PB). Maintenance obinutuzumab (MO) was omitted for patients with imaging complete response (CR) and MRD-negativity in PB/BMA. All other patients received 8 cycles MO. Primary endpoint is PFS; secondary endpoints are response rates, overall survival, and estimation of MRD status.</div></div><div><h3>Results</h3><div>Twenty-one patients enrolled, with median age 70 years and stage IV disease in 95%. Twenty patients completed BO; 10 patients received MO per protocol. Six patients did not complete MO due to progression (n = 4), infection (n = 1) and carcinoma (n = 1). Overall response is 95% (75% CR, 20% partial response). Concordance rate between post-consolidation MRD testing in PB and BMA was 70%.</div><div>After a median follow-up of 43.9 months, median PFS is 46.5 months. The observed difference between 2-year PFS in groups receiving MO versus observation was not statistically significant (HR 0.45, 95% CI, 0.10-1.91). Most common grade 3/4 toxicities were neutropenia, leukopenia, and infections.</div></div><div><h3>Conclusions</h3><div>BO is a tolerable induction regimen with higher rates of CR compared with historical rates with bendamustine + rituximab. Omission of MO did not worsen outcomes in patients achieving MRD-negative status after nonintensive induction/consolidation therapy.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"25 3","pages":"Pages 188-198"},"PeriodicalIF":2.7,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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