Featured
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Research Highlight |
Tabelecleucel is effective in EBV-positive lymphoproliferative disease
- Diana Romero
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Research Highlight |
PERSEUS triumphs — efficacy of daratumumab confirmed in transplant-eligible NDMM
- David Killock
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Review Article |
Quantitative PET-based biomarkers in lymphoma: getting ready for primetime
Despite advances in drug development for patients with lymphoma over the past decades, the identification of biomarkers for treatment selection remains an unmet need. The authors of this Review provide an overview of quantitative PET-based biomarkers in this patient population and discuss the challenges and opportunities in the integration of these biomarkers in clinical trials and the routine management of patients with lymphoma.
- Juan Pablo Alderuccio
- , Russ A. Kuker
- & Craig H. Moskowitz
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News & Views |
A critical appraisal of the ATLAS trial of maintenance therapy for multiple myeloma: end points, censoring and equipoise
A recent report from the ATLAS trial comparing different maintenance strategies following haematopoeitic stem cell transplantation for multiple myeloma provides an opportunity to explore various themes of critical appraisal, including end points, the equipoise of trial design, and the part censoring can play in the validity of results.
- Ghulam Rehman Mohyuddin
- & Tomer Meirson
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Research Highlight |
Venetoclax–obinutuzumab combinations are effective in fit patients with CLL
- Diana Romero
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News & Views |
Determinants of response and resistance to T cell-engaging therapies in multiple myeloma
Bispecific T cell engagers offer a novel treatment approach for patients with multiple myeloma, although mechanisms of resistance are largely unknown. Here, we discuss the implications of a recent report from Friedrich et al. that highlights the importance of pre-treatment T cell characteristics for a response to the T cell engager elranatamab and how these data might be used to inform future study and trial design.
- Shonali Midha
- & Kenneth C. Anderson
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Review Article |
Long-term outcomes following CAR T cell therapy: what we know so far
Chimeric antigen receptor (CAR) T cells have dramatically improved the outcomes of patients with certain relapsed and/or refractory haematological malignancies. Owing to the promising short-term survival outcomes achieved, long-term data on both safety and survival are becoming increasingly relevant. In this Review, the authors describe the available long-term follow-up data from early studies testing the safety and efficacy of receiving CAR T cells targeting CD19 as well as more recent data on BCMA-targeted CAR T cells in patients with relapsed and/or refractory multiple myeloma.
- Kathryn M. Cappell
- & James N. Kochenderfer
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Comment |
GPRC5D as a novel immunotherapeutic target in multiple myeloma
The development of modern immune-based therapies for multiple myeloma has expanded rapidly over the past several years, and GPRC5D has been identified as a viable immunotherapeutic target. Herein, we discuss data and provide future perspectives on GPRC5D-directed CAR T cells and bispecific antibodies for patients with relapsed and/or refractory multiple myeloma.
- Karthik Nath
- , Bruno A. Costa
- & Sham Mailankody
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News & Views |
Clash of the titans: axi-cel versus tisa-cel for advanced-stage DLBCL
CAR T cell therapy has altered the natural history of relapsed and/or refractory diffuse large B cell lymphoma (DLBCL). However, the availability of multiple products has created provider uncertainty regarding treatment selection and the need to balance toxicity and efficacy. In a retrospective analysis, the authors suggest that axicabtagene ciloleucel might be superior to tisagenlecleucel. However, several questions remain unresolved.
- Richard T. Maziarz
- & Jordan Gauthier
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News & Views |
When an embarrassment of riches isn’t enough
Data on a new treatment approach utilizing bispecific monoclonal antibodies targetting B-cell maturation antigen (BCMA) were recently published, yielding very encouraging results in the setting of relapsed and/or refractory multiple myeloma (RRMM). How to safely and effectively deliver this treatment to patients and where it fits in the RRMM treatment paradigm are important questions for the future.
- Krina Patel
- & Sagar Lonial
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Comment |
Overall survival as a primary end point in multiple myeloma trials
Median overall survival for patients with newly diagnosed multiple myeloma may surpass ten years. Nonetheless, many patients face considerable treatment-related morbidity and relapsed disease. Owing to this typically long overall survival, most multiple myeloma trials now use progression-free survival as their primary end point. In this Comment, we highlight circumstances in which this end point does not best answer the questions that various trials seek to investigate.
- Edward R. Scheffer Cliff
- & Ghulam Rehman Mohyuddin
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Review Article |
Preparing for CAR T cell therapy: patient selection, bridging therapies and lymphodepletion
Chimeric antigen receptor T cells have revolutionized the treatment of patients with certain haematological malignancies. Nonetheless, an optimal approach to lymphodepleting chemotherapy and/or bridging therapies has yet to be defined in patients receiving these agents. In this Review, the authors describe the various lymphodepletion and/or bridging therapy strategies used, and highlight the need for prospective comparisons in order to determine the safest and most effective approach.
- Leila Amini
- , Sara K. Silbert
- & Mohamed Abou-el-Enein
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Review Article |
Single-cell profiling of tumour evolution in multiple myeloma — opportunities for precision medicine
Multiple myeloma and its precursor stages, monoclonal gammopathy of undetermined significance and smouldering multiple myeloma, have a considerable degree of genetic heterogeneity. The authors of this Review discuss how single-cell studies in these individuals are enabling the mutational and phenotypic characterization of cells within the bone marrow tumour, immune microenvironment and peripheral blood to eventually guide early diagnosis, risk stratification and treatment strategies.
- Ankit K. Dutta
- , Jean-Baptiste Alberge
- & Irene M. Ghobrial
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Research Highlight |
Contrasting results with second-line CAR T cells in large B cell lymphoma
- Diana Romero
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Comment |
Daratumumab in newly diagnosed MM — incorporating lessons learnt from CASSIOPEIA, MAIA and beyond
Daratumumab is an anti-CD38 monoclonal antibody that has transformed the landscape of treatment both for transplant-eligible and -ineligible patients with newly diagnosed multiple myeloma. Addressing important ongoing questions, such as when to de-escalate therapy, will be an important step forward in delivering patient-centred care for those with newly diagnosed multiple myeloma.
- Ghulam Rehman Mohyuddin
- & Hira Mian
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News & Views |
Anti-CD7 CAR T cells for T-ALL: impressive early-stage efficacy
Chimeric antigen receptor (CAR) T cells have remarkable efficacy in patients with B cell acute lymphoblastic leukaemia (ALL), but have not been successful to date in patients with T cell ALL (T-ALL). Now, data from Pan and colleagues demonstrate the safety and impressive short-term efficacy of allogeneic donor-derived anti-CD7 CAR T cells in an early-phase clinical trial involving patients with relapsed and/or refractory T-ALL.
- David T. Teachey
- & Stephen P. Hunger
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Comment |
Practicing on the edge of oncology: when standard of care feels uncomfortable
The treatments oncologists deliver are generally based on evidence from large randomized controlled trials, consistent with practice guidelines, and congruent with the treatments selected by our peers. In this Comment, we use two scenarios to highlight the discomfort clinicians might feel when they are outliers from the guideline-recommended standard of care.
- Christopher M. Booth
- & Aaron M. Goodman
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News & Views |
Whole-genome sequencing for myeloid disease: one assay to stratify them all?
Whole-genome sequencing of samples from patients with myeloid malignancies can enable more accurate risk stratification than is possible with conventional cytogenetics. Research by Duncavage et al. demonstrates that such an approach can now be delivered within several days using a highly streamlined and automated workflow.
- Karilyn T. M. Larkin
- & John C. Byrd
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Review Article |
Towards precision medicine for AML
Advances in sequencing technology have rapidly improved our understanding of the biology of acute myeloid leukaemia and led to the development of several novel targeted therapies. In this Review, the authors summarize the landscape of novel targeted therapies for patients with acute myeloid leukaemia and provide guidance on future research directions.
- Hartmut Döhner
- , Andrew H. Wei
- & Bob Löwenberg
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Current understanding and management of CAR T cell-associated toxicities
Promise with co-administration of CAR T cells
Engaging results with glofitamab