Issue Archive

Although there have been many therapeutic advances in follicular lymphoma (FL) in recent years, important questions remain about how best to integrate emerging biologic insights with evolving treatment options. To address these challenges, Associate Editor Philippe Armand has assembled a comprehensive review series. Araujo-Ayala and Béguelin highlight recent advances in the biological understanding of FL, including its evolutionary pathways and therapeutic vulnerabilities. Bachy and Linton examine the challenges of designing and conducting frontline clinical trials and propose strategies to overcome them. Casulo and Sehn outline a personalized approach to managing relapsed or refractory FL. Mulvey et al explore the promise of novel assays and treatments that may shape the next era of FL care. Di et al consider key issues in trial design, particularly given the prolonged benefit seen with many current therapies. Parry and Okosun review the biology of histologic transformation and its clinical management, which is still one of the most difficult aspects of FL treatment.

While retrospective studies suggest a potential advantage of busulfan-melphalan (BUMEL) over standard high-dose melphalan (MEL200) conditioning for transplant-eligible newly diagnosed multiple myeloma, the benefit remains uncertain. Lahuerta et al report results of the phase 3 GEM12 trial directly comparing BUMEL with MEL200 in the context of an intensified bortezomib-lenalidomide-dexamethasone–based first-line approach. Both deliver excellent progression-free survival (PFS) and overall survival; a longer PFS was seen with BUMEL in patients with International Staging System (ISS) stage II-III disease and in those with high-risk cytogenetics [del(1p) or t(14;16)], whereas MEL200 was superior in ISS stage I disease. Despite the rapid evolution of frontline myeloma therapy, this well-conducted study suggests a possible role for intensified consolidation with BUMEL for selected patients.

Although there have been many therapeutic advances in follicular lymphoma (FL) in recent years, important questions remain about how best to integrate emerging biologic insights with evolving treatment options. To address these challenges, Associate Editor Philippe Armand has assembled a comprehensive review series. Araujo-Ayala and Béguelin highlight recent advances in the biological understanding of FL, including its evolutionary pathways and therapeutic vulnerabilities. Bachy and Linton examine the challenges of designing and conducting frontline clinical trials and propose strategies to overcome them. Casulo and Sehn outline a personalized approach to managing relapsed or refractory FL. Mulvey et al explore the promise of novel assays and treatments that may shape the next era of FL care. Di et al consider key issues in trial design, particularly given the prolonged benefit seen with many current therapies. Parry and Okosun review the biology of histologic transformation and its clinical management, which is still one of the most difficult aspects of FL treatment.

Although there have been many therapeutic advances in follicular lymphoma (FL) in recent years, important questions remain about how best to integrate emerging biologic insights with evolving treatment options. To address these challenges, Associate Editor Philippe Armand has assembled a comprehensive review series. Araujo-Ayala and Béguelin highlight recent advances in the biological understanding of FL, including its evolutionary pathways and therapeutic vulnerabilities. Bachy and Linton examine the challenges of designing and conducting frontline clinical trials and propose strategies to overcome them. Casulo and Sehn outline a personalized approach to managing relapsed or refractory FL. Mulvey et al explore the promise of novel assays and treatments that may shape the next era of FL care. Di et al consider key issues in trial design, particularly given the prolonged benefit seen with many current therapies. Parry and Okosun review the biology of histologic transformation and its clinical management, which is still one of the most difficult aspects of FL treatment.

Although there have been many therapeutic advances in follicular lymphoma (FL) in recent years, important questions remain about how best to integrate emerging biologic insights with evolving treatment options. To address these challenges, Associate Editor Philippe Armand has assembled a comprehensive review series. Araujo-Ayala and Béguelin highlight recent advances in the biological understanding of FL, including its evolutionary pathways and therapeutic vulnerabilities. Bachy and Linton examine the challenges of designing and conducting frontline clinical trials and propose strategies to overcome them. Casulo and Sehn outline a personalized approach to managing relapsed or refractory FL. Mulvey et al explore the promise of novel assays and treatments that may shape the next era of FL care. Di et al consider key issues in trial design, particularly given the prolonged benefit seen with many current therapies. Parry and Okosun review the biology of histologic transformation and its clinical management, which is still one of the most difficult aspects of FL treatment.

Although there have been many therapeutic advances in follicular lymphoma (FL) in recent years, important questions remain about how best to integrate emerging biologic insights with evolving treatment options. To address these challenges, Associate Editor Philippe Armand has assembled a comprehensive review series. Araujo-Ayala and Béguelin highlight recent advances in the biological understanding of FL, including its evolutionary pathways and therapeutic vulnerabilities. Bachy and Linton examine the challenges of designing and conducting frontline clinical trials and propose strategies to overcome them. Casulo and Sehn outline a personalized approach to managing relapsed or refractory FL. Mulvey et al explore the promise of novel assays and treatments that may shape the next era of FL care. Di et al consider key issues in trial design, particularly given the prolonged benefit seen with many current therapies. Parry and Okosun review the biology of histologic transformation and its clinical management, which is still one of the most difficult aspects of FL treatment.

Although there have been many therapeutic advances in follicular lymphoma (FL) in recent years, important questions remain about how best to integrate emerging biologic insights with evolving treatment options. To address these challenges, Associate Editor Philippe Armand has assembled a comprehensive review series. Araujo-Ayala and Béguelin highlight recent advances in the biological understanding of FL, including its evolutionary pathways and therapeutic vulnerabilities. Bachy and Linton examine the challenges of designing and conducting frontline clinical trials and propose strategies to overcome them. Casulo and Sehn outline a personalized approach to managing relapsed or refractory FL. Mulvey et al explore the promise of novel assays and treatments that may shape the next era of FL care. Di et al consider key issues in trial design, particularly given the prolonged benefit seen with many current therapies. Parry and Okosun review the biology of histologic transformation and its clinical management, which is still one of the most difficult aspects of FL treatment.

Although there have been many therapeutic advances in follicular lymphoma (FL) in recent years, important questions remain about how best to integrate emerging biologic insights with evolving treatment options. To address these challenges, Associate Editor Philippe Armand has assembled a comprehensive review series. Araujo-Ayala and Béguelin highlight recent advances in the biological understanding of FL, including its evolutionary pathways and therapeutic vulnerabilities. Bachy and Linton examine the challenges of designing and conducting frontline clinical trials and propose strategies to overcome them. Casulo and Sehn outline a personalized approach to managing relapsed or refractory FL. Mulvey et al explore the promise of novel assays and treatments that may shape the next era of FL care. Di et al consider key issues in trial design, particularly given the prolonged benefit seen with many current therapies. Parry and Okosun review the biology of histologic transformation and its clinical management, which is still one of the most difficult aspects of FL treatment.

Bispecific antibodies (BsAbs) that simultaneously bind a tumor-associated antigen (such as CD20) and the CD3 ε subunit on T cells have demonstrated strong activity in relapsed B-cell lymphoma and are now being evaluated earlier in the treatment course and in combination strategies. Sam et al leveraged humanized mouse models to investigate the efficacy of glofitamab, a CD20×CD3 BsAb, in combination with multiple therapeutic modalities and demonstrated that glofitamab combined with chemotherapy or antibody-drug conjugates produces marked synergy. These findings provide a rational framework for the design of clinical trial combinations with BsAbs.

While the bone marrow (BM) microenvironment influences multiple myeloma (MM) biology, the precise nature of these interactions remains poorly understood. Yip et al applied spatial transcriptomics to BM trephine biopsies from patients with precursor plasma cell dyscrasias and newly diagnosed MM to investigate the interplay between plasma cell subpopulations and their surrounding microenvironment. They did not observe a conserved tumor microenvironment (TME), finding that differences in cellular composition between distinct intratumoral neighborhoods are more pronounced than those observed between precursor stages and MM, and there were no consistent TME changes across disease stages. These findings challenge the prevailing assumption that broad, BM-wide microenvironmental changes are the primary drivers of progression in plasma cell disorders.

Plasminogen (Plg), the zymogen precursor of plasmin, is well known for its central role in fibrinolysis and its ability to regulate macrophage phenotypes and inflammation. Michell et al identified an unexpected function of Plg as a carrier of small noncoding RNAs (sRNAs) that promote both immune cell activation and clotting. This discovery positions Plg-sRNA interactions as promising therapeutic targets for the treatment of thrombotic and inflammatory diseases.