No images? Click here Women in Lymphoma Newsletter - Issue 8 - December 2023 Edited by Dr Michelle Poon (Singapore) & Dr Clémentine Sarkozy (France) Founded in 2019, Women in Lymphoma is a global collaborative alliance of over 1,000 professionals in 62 countries engaged in lymphoma treatment, research and education. WiL members have a breadth of research skills and capacity across basic and translational research, clinical trials, implementation science and patient-clinician research collaborations.Women in Lymphoma is committed to support and advocate for greater leadership of women in lymphoma; to inspire and empower women in lymphoma; identify and track the metrics of such engagement, and be a voice to challenge and change inequity in lymphoma leadership around the world. Founding members of WiL include past and current presidents of ASH/ASCO, Chair-Elect of the SAB Lymphoma Research Foundation (US), Chief Medical Officer of LYSA, the leading French lymphoma Study Association; lymphoma leads of the ALLG (Australia), Dutch HOVON group, British Society of Haematology, Founding Chair of Australasian Lymphoma Alliance (ALA) and haematologists from leading cancer centres around the world. Women in Lymphoma creates and builds initiatives including the WiLing Wednesdays educational webinars; the Change Champions Committee - comprising seven leading male lymphoma specialists with WiL Steering Committee members; global cooperative surveys in gender metrics; annual awards for outstanding Women in Lymphoma; an active social media presence; regular newsletter and representation at leading lymphoma conferences. Women in Lymphoma acknowledges the enabling support of Lymphoma Australia www.lymphoma.org.au Women in Lymphoma Steering Committee 2023 • Chair - Carla Casulo (USA) • Immediate Past Chair - Ann LaCasce (USA) • Secretary - Paola Ghione (USA) • • Florence Broussais (France) • Kate Cwynarski (UK) • Eliza Hawkes (Australia) • Justine Kahn (USA) • • Sharyn Kurtz (USA) • Kim Linton (UK) • Carolina Mahuad (Argentina) • Monique Minnema (The Netherlands) • Loretta Nastoupil (USA) • Wendy Osborne (UK) • Astrid Pavlovsky (Argentina) Michelle Poon (Singapore) • • Clémentine Sarkozy (France) • Laurie Sehn (Canada) • Sonali Smith (USA) • Anna Sureda Balari (Spain) • • Carrie Thompson (USA) • Judith Trotman (Australia) • Julie Vose (USA) • 65th ASH annual Meeting and Exposition Lymphoma review by Dr Carolina Mahaud (Argentina) for WiL This year at ASH https://www.hematology.org/meetings/annual-meeting more than 7,000 papers were presented, with approximately 1,000 selected for oral presentation. This clearly shows how difficult it is to select the best presentations. In this piece, we summarise some of the most relevant information on lymphoproliferative neoplasms. With respect to aggressive B-cell lymphomas, there was an Educational Session chaired by Manali Kamdar, MD (University of Colorado Medicine, Denver CO, USA), in which Dr. Ana Sureda (Hospitalet de Llobregat, Barcelona, Spain) discussed different prognostic and predictive markers that have arisen from clinical trials. Dr. Sureda presented different pre-infusion, post-infusion and post-CAR T-cell relapse prognostic factors influencing the outcomes of anti CD19 CAR T-cell therapy in patients with relapsed and refractory B-cell lymphomas. Despite the overall positive results in this population with the introduction of CAR T-cell therapy, a significant percentage of patients will relapse. Therefore it is crucial to interpret how the presence of risk factors could have an impact on treatment or a follow-up approach. In the same session, Loretta J. Nastoupil, MD (MD Anderson Cancer Center, Houston TX, USA) presented an algorithm for the management of aggressive Lymphomas that fail CAR T-cell therapy. In this talk the prospective studies that inform treatment options in later lines were reviewed and, also highlighted the limited data examining outcomes with novel therapies after CAR T-cell failure. Bispecific antibodies appear to be a promising approach, particularly after CAR T-cell therapy, although very little is known about overlapping mechanisms of resistance. Finally in this session, Manali Kamdar, MD provided different tools to select between CAR T-cell therapy and Bispecific Antibodies and how to sequence these therapies in this clinical scenario. The real-world efficacy and safety of CAR T therapies were presented as well as the comparison of the advantages and disadvantages of initial sequencing of CAR T first vs bispecific antibodies first in relapsed and refractory large B-cell lymphomas. In the Q&A session, topics including access in different countries, costs and toxicities were discussed. In the oral sessions, these topics were presented in depth through prospective and real-world evidence studies. There have been numerous presentations positioning bispecific antibodies as a useful therapeutic tool in patients previously treated with CAR T-cell therapy. Dr Martin Hutchings (Rigshospitalet, Copenhagen, Denmark) presented the results of Glofitamab Monotherapy in R/R DLBCL: extended follow-up from a pivotal phase II Study in patients relapsed after CAR T. 155 patients were enrolled. The overall response and CR rates were 52% and 40% respectively. The majority of CRs (65%) were ongoing at data cut-off. No safety signals were observed. Data from subgroup analysis showed that higher baseline TMTV was associated with an increased risk of grade 2 CRS and suggested that baseline TMVT may be prognostic for PFS. The finite duration of treatment is considered a very relevant aspect, considering costs and treatment-induced toxicities. The results presented by Sabarish Ram Ayyappan, MD (City of Hope, Atlanta GA, USA) on Odronextamab in a similar clinical scenario in 141 patients evaluable for safety and 127 for efficacy, shows an ORR and CR rate of 52% and 31%, respectively, with a median DoR of 10.2 months and median duration of CR of 17.9 months. The benefit of the drug was maintained even in patients with high-risk features. Minretumomab administered subcutaneously plus Polatuzumab Vedotin (Elizabeth Lihua Budde, MD – City of Hope, Los Angeles) achieved an ORR of 62% (across patients that have received prior CAR-T therapy and primary refractory patients) with a CR rate of 50%, even in patients that have relapsed after CAR T-cell and primary refractory. Prof. Chan Yoon Cheah (Breakthrough Haematology, Perth, Australia) also presented the efficacy of Mosunetuzumab monotherapy in patients with relapsed or refractory Richter`s Transformation (ORR 40%, CR 20%). Prof. Won Seog Kim (Sungkyunkwan University School of Medicine, Seoul, Korea) presented the results from EPCORE NHL-5 (Subcutaneous Epcoritiamb plus Lenalidomide in patients with R/R DLBCL): the overall response rate was 75%. Complete metabolic responses were seen in 58% of patients with a median time to first response of 1.8 months, showing that Epcoritamab combined with lenalidomide has a promising antitumor activity with tolerable safety profile. With respect to Hodgkin Lymphoma, probably the most relevant evidence presented in this edition of ASH - also selected within the framework of the best of ASH - was the work presented by Sarah Rutherford, MD (Weill Cornell Medicine, New York NY, USA) - Nivolumab-AVD is better tolerated and improves PFS compared to BV -AVD in older patients with advanced stage HL enrolled on SWOG S1826. In this subset, the median follow-up was 12.1 months. 1-yr PFS was superior in the N-AVD arm (93% vs 64%). 1-yr-EFS was 93% for N-AVD and 57% for Bv-AVD with a 1-yr-OS of 95% and 83%, respectively. N-AVD is poised to become a standard of care for older advanced-stage HL patients fit for anthracycline-based combination therapy. Regarding Peripheral T lymphomas, Jonathan E. Brammer, MD (Ohio State University Comprehensive Cancer Center, Columbus OH, USA) presented the results of the phase I/II study: Post-allograft Romidepsin maintenance mitigates relapse risk and stimulates the graft versus-malignancy effect through enhanced NK-cell cytotoxicity in patients with T-cell malignancies. BuFluRom with Romidepsin maintenance showed to be effective at decreasing relapse in patients with PTCL, with 1-year CI relapse below expected relapse rates for this set of diseases, meeting the pre-specified efficacy endpoint. Romidepsin maintenance enhances NK-cell cytotoxicity Post-Allogeneic SCT, increasing the GVL effect and likely accounting for at a minimum, some of the decrease in relapse seen in this trial. Regarding Follicular Lymphoma, Stephen J. Schuster, MD (Penn Medicine, Philadelphia PA, USA) presented the 3-year follow-up of the phase 2 Elara trial. 97 patients with relapsed/refractory follicular lymphoma treated with at least two previous therapeutic lines were treated with Tisagenlecleucel. A first report was made at 17 months of follow-up, demonstrating high response rates and a favorable safety profile. In this edition of ASH, the results after more than 3 years of follow-up were reported. ORR was 86%, with a mean PFS of 37 months. In the POD24 subgroup, the 36-month PFS was 53% vs 69% in patients without POD24. The authors concluded that Tisagenlecleucel maintained a high rate of durable responses, including in high-risk subgroup of patients. The safety profile remained favorable with no new safety signals. Correlative analysis suggested that higher baseline levels of CD8+ naive T-cells were associated with improved long-term clinical outcomes. Dr. Schuster also presented the 3-year follow-up from the pivotal Phase II trial: Mosunetuzumab monotherapy in patients with R/R FL. In this trial, patients achieving CR by C8 completed treatment without additional cycles; patients with a partial response or stable disease received a total of 17 cycles. 90 patients were enrolled. The ORR and CR were 77.8% and 60%, respectively. The estimated 30-month DOCR rate was 72.4%. The median PFS was 24 months, median TTNT was 37.7 months and the estimated EFS at 36 months was 52%. In this updated analysis, a durable response continued to be observed with fix-duration Mosunetuzumab in patients with R/R FL. The safety profile was also consistent with previous reports. Interestingly, evidence of B-cell recovery was observed after a median of 18 months following the end of treatment. In the 1L treatment scenario in FL, Mosunetuzumab sc, finite treatment, demonstrated high efficacy even in high-burden FL, including those with higher-risk disease with an acceptable safety profile both as monotherapy and in combination with lenalidomide (Paper No. 0604 and No. 0605 presented by Lorenzo Falchi, MD (Memorial Sloan Kettering Cancer Center, New York NY, USA) and Prof. Franck Morschhauser, (CHU Lille, France) respectively). In the scenario of R/R Mantle Cell Lymphoma, the work presented by Michael Wang, MD (MD Anderson Cancer Center, Houston TX, USA) in the “Late Breaking Abstracts” session was highlighted: the Sympatico trial is a phase 3 RCT, in which MCL patients, refractory or relapsed to at least one therapeutic line, were randomized to receiving Ibrutinib + Venetoclax vs Ibrutinib + placebo. The results of the interim analysis were presented in this session. This chemotherapy-free treatment was sustained for 24 months. The PFS was 32 months vs 22 months across different subgroups. TTNT was 60 months vs 42 months. CR rates were 54 vs 32% (p ≤0.0004) and OS 45 vs 39 months, NS. The results are very encouraging for a population of patients with a poor prognosis. These results should still be taken with caution given the short follow-up. Dr. Morgane Cheminant (Hôpital Necker-Enfants Malades, Paris, France) presented Paper No. 299: Validation of POD24 as a robust early clinical end point of poor survival in MCL from 1280 patients on clinical trials. The analysis of this large dataset of patients included in clinical trials, confirmed that POD24 can be used as a surrogate for OS in MCL. ASCT as well as rituximab maintenance have not a clear benefit to prevent early relapse within two years after the diagnosis in responding patients at the end-of-induction.
Gender Equity in Academic Hematology: Where There’s a WiL, There’s a Way by Dr Eliza Hawkes & Carla Casulo, MD
Gender diversity, equity, and inclusion (DEI) in medicine has long proven to lead to benefits in innovation, collaboration and workplace culture. However, the data continues to showcase challenges in achieving these goals despite women comprising 50% of the general population and 50% of medical graduates in most developed countries since the early 2000s. In this Lancet article and accompanying discussion in the ASCO post, Drs Hawkes and Casulo highlight the low female representation in lymphoma journal reviews, commentaries and editorials in the eight leading journals in this field as well as low representation in most major conference steering committees and invited speakers despite women consistently comprising 50% of attendees. In this thoughtful and insightful commentary, the authors also explore reasons contributing to this inequity including both conscious and unconscious biases within the system. They also explore key ways to address these issues and the hopes of Women in Lymphoma for a much-improved future. We encourage WIL members and supporters to read this Lancet paper and ASCO post commentary and to continue to collaboratively advocate, analyse and motivate global academic and clinical organisations to achieve gender equity in lymphoma and across medicine. New articles published by WiL + discussions by lead authors 1. How I treat secondary CNS involvement by aggressive lymphomas. Alderuccio JP, Nayak L, Cwynarski K. Blood. 23 November, 2023. www.sciencedirect.com/science/article/pii/S0006497123022097?dgcid=author Online ahead of print. Kate Cwynarski : A pleasure to discuss the management of SCNSL with Juan Alderuccio (Miami USA) and Laksmi Nayak (Dana-Farber Cancer Institute, Boston). The treatment landscape is rapidly changing with resultant improvement in outcome for this challenging clinical scenario.
2. Long-term follow-up of Rituximab maintenance in young patients with mantle cell lymphoma included in the LYMA trial, a LYSA study. Hematological Oncology. 9 June, 2023. https://onlinelibrary.wiley.com/doi/full/10.1002/hon.3163_100 Clémentine Sarkozy: We show this long term FU that rituximab maintenance provide a prolonged benefit in term of PFS, with a trend for OS, without increase in the relapse incidence after the end of maintenance, or increase in infectious related mortality. Importantly, POD24 patients have a very poor outcome and MCL patients should be included in clinical trials based on high risk features identified as associated with this event.
3. Disparities in care and outcomes for adolescent and young adult lymphoma patients. Allison Rosenthal, Adam Duvall, Justine Kahn, Niloufer Khan EJH. 2023 Sept 2023 https://doi.org/10.1002/jha2.797 Justin kahn: The EJH paper is a review on the unique challenges that AYAs with lymphoma face from diagnosis through up-front therapy and long into survivorship. We discussed diagnostic delays, access-related issues, and the urgent need to improve health equity and quality of care for socially vulnerable AYA lymphoma populations.
4. Two recent large studies published looking at the role of intravenous methotrexate for CNS prophylaxis for patients with high risk Diffuse Large B cell lymphoma. Authors were asked how these findings might affect their management of the patients. a) Diffuse large B‐cell lymphoma at risk of secondary CNS involvement: The inefficacy of intravenous high‐dose methotrexate CNS prophylaxis and the importance of baseline cerebrospinal fluid analysis. Rory Bennett, Anna Ruskova, Christin Coomarasamy, Edward Theakston, Leanne Berkahn, Sharon Jackson, Mina Christophers, Stephen Wong, Samar Issa b) High-Dose Methotrexate as CNS Prophylaxis in High-Risk Aggressive B-Cell Lymphoma. • Katherine Lewis: Over the last few years, there’s been an growing body of retrospective data suggesting that systemic methotrexate (HD-MTX) for CNS prophylaxis in DLBCL may not be effective at presenting CNS relapse, and mounting interest in this topic. However, studies exclusively investigating this in large numbers of high-risk patients are scarce, and there had been no randomized studies investigating this at the time of initiation of our study. There has since been a small randomized study investigating intrathecal and intravenous methotrexate for CNS prophylaxis, suggesting no
benefit to IV HD-MTX, but too small to definitively draw this conclusion.
• Samar et al High-dose intravenous methotrexate (HD-MTX) for CNS prophylaxis in high-risk diffuse large B cell lymphoma (DLBCL) patients was the standard of care in New Zealand, as well as in many other parts of the world, based on published recommendations. The treatment requires 5-7 days of hospital admission to administer the chemotherapy and is associated with high risk of organ toxicity including liver and kidneys and increased risk of infections. Emerging data, including Katherine’s 2021 American Society of Hematology conference presentation were pointing towards lack of benefit in reducing this risk in statistically significant manner. We used the Auckland/ New
Zealand regional Lymphoma Database to look at the five-year CNS relapse incidence and survival outcomes, as stratified by the receipt of 2-4 cycles of IV HD-MTX 3g/m2 prophylaxis, in 445 consecutive high risk DLBCL patients. The HD-MTX was given either intercalated (majority of patients) or/ at the conclusion of the systemic chemotherapy treatment. We found no significant difference in the 5-year CNS relapse incidence with prophylaxis versus no prophylaxis; 6.2% versus 5.6% [HR 1.08, p = .88]. There was no difference in 5-year progression free survival or overall survival risk in this group of patients. On the other hand, our data showed possible survival advantage in the subgroup of DLBCL patients with leptomeningeal involvement (positive CSF by cell marker studies) at diagnosis who were treated with high intensity CNS directed as well as systemic chemotherapy therapies versus those who
presented with CNS relapse including those who received HD-MTX prophylaxis (HR 0.55, P=0.052). • Kate Cwynarski: We haven't stopped prophylaxis yet. However we increasingly image/CSF studies. With these new data, we plan to work together to review our UK guidance. • Pam McKay (Lead author for the British Society of Haematology Good Practice paper 2020): We are in the process of updating the Good Practice Paper.We see enough patients to retain a degree of caution when thinking of abandoning IV MTX prophylaxis completely. That said it has toxicities and given all the retrospective data suggesting lack of benefit, we have significantly curtailed the number of patients who we offer this to – no longer offer to older patients, borderline renal function or IPI of 4. We continue to discuss in the few patients in the very HR subgroups who might benefit especially those who are young and with renal/adrenal and multiple EN sites (as well as testicular).Whilst I agree we need to be more pro-active in looking for CSF involvement at diagnosis I think this is challenging and would need to be restricted to very HR group – otherwise numbers would be too great to accommodate the LPs and MRIs in appropriate time scale to avoid compromising start of 1st line therapy.” ________________________________________________________ New roles and promotions for WiL Steering Committee members Eliza Hawkes - Associate Editor for eJH, lymphoid malignancies https://onlinelibrary.wiley.com/page/journal/26886146/homepage/editorialboard.html Medical oncologist and lymphoma lead at the Olivia Newton John Cancer Research & Wellness Centre, Austin Health, a National Health and Medical Research Council Investigator, Associate Professor at Monash University in Melbourne Australia
Florence Broussais After 15 years as a hematologist, with two boys, and 7 years as medical director of LYSARC, an academic research organization, I wanted to put my life into perspective. My husband had the opportunity to work in New York. My mentor had just moved there, so I saw an alignment of the planets. The 4 of us left to experience the hectic energy of Manhattan. I worked for the Institute for Follicular Lymphoma Innovation (IFLI), a global, multi-arm, non-profit, private foundation dedicated to accelerating the development of innovative treatment options for people with follicular lymphoma. I worked to set up a "moonshot initiative" - a worldwide RFP dedicated to supporting advances in understanding the biology of follicular lymphoma and transformed FL to accelerate the development of innovative treatment options and ultimately develop a cure. A year in the US involves encounters, discovering other social codes, motivation, and cultural difference. It reaffirmed the importance of my work as a powerful driving force for personal fulfillment. After the hematologist's singular relationship with their patients and the team manager position in clinical research, my new challenge was understanding the private sector to develop and improve academic research. I am back in France now. I have just joined CALYM, a consortium of academic research institutes dedicated to lymphoma research, and strongly committed to developing partnership-based research with the pharma and tech companies. WiL Founder, Judith Trotman told me 10 years ago: “pace yourself and remain calm but resolute with life's challenges”. Judith's confidence has been a precious gift to fuel my career. I'm delighted to be able to share my experience with WIL and hope to give back all I have received. ________________________________________________________ WiLing Wednesdays free Educational Webinars In 2023 WiL offered 11 free educational webinar sessions: - Series 8 – Chronic Lymphocytic Leukaemia (CLL) – 4 sessions – February/March 2023 - Series 9 – Mantle Cell Lymphoma (MCL) – 3 sessions – May 2023 - Series 10 – Career Development – 4 sessions – October/November 2023 Webinar Recordings https://womeninlymphoma.org/events-%26-news - Series 11 is planned for early 2024 and will focus on DLBCL - re-visiting and updating the first WiL webinar series in September 2020.
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