New and Old Cellular Therapies for Advanced Lymphoid Neoplasms

The introduction of new cellular therapies has revolutionized the treatment of advanced lymphoid neoplasms bringing the chance for cure in patients previously doomed to best supportive care. Currently, about a dozen CAR-T cell products have been approved for clinical use worldwide,1 of which 7 have been approved by FDA and EMA for lymphoid neoplasms: 5 target the pan-B antigen CD19 allowing use in B-cell acute lymphoblastic leukaemia (B-ALL) and several B-cell lymphoma histotypes, while 2 are directed to the B-cell maturation antigen, which is generally expressed at high levels in multiple myeloma. In this setting, even more approvals have been granted to bispecific antibodies, which similarly leverage a T-cell engaging mechanism – a therapeutic principle that ultimately stems from the oldest cellular therapy, i.e. allogeneic transplantation (allo-SCT). While further trials, approvals, and novel products are highly anticipated for CAR-T and bispecific therapies, therapeutic progress has also significantly improved the safety and antitumor efficacy of allo-SCT. Therefore, new cellular therapies are not necessarily meant to replace older ones, but rather to integrate and complement them within the treatment paradigm.

Despite unprecedented progress in the field of advanced lymphoid malignancies, the clinical reality is that the majority of relapsed/refractory patients, even if treated with novel cellular therapies, will ultimately relapse. Consequently, a significant proportion of these patients will likely require more than one cellular therapy, old or new, over the course of their disease.
This newly unveiled scenario underscores the critical necessity of understanding and managing the interaction among new and old cellular therapies, by defining the limitations and advantages of combining or sequencing these treatments.
Evidence for this is already apparent across the three major therapeutic areas for advanced lymphoid malignancies—B-ALLs, lymphomas, and myeloma—where a substantial fraction of patients treated with bispecific antibodies had already been exposed to CAR-T therapies (and/or vice-versa). Meanwhile, allo-SCT continues to be a clinically relevant option, frequently discussed for both consolidation and salvage settings, not least because it first provided the proof of principle of cure for these diseases.
We welcome Original Research, Review, Mini Review and Perspective articles on themes including, but not limited to:
• Sequential or concomitant efficacy and safety data of cellular therapies (CAR-T, allo-SCT, etc.) or cellular-engaging therapies (bispecific antibodies) in B-ALL, lymphomas and myelomas.
• Strategies to improve the efficacy and/or toxicity profile of cellular therapies (CT) or cellular-engaging therapies (CET) in higher risk patients with lymphoid neoplasms through combinatorial, sequential or salvage approaches or treatment optimization (e.g. modification prophylaxis for CRS or GVHD, changes to lymphodepletion or conditioning regimens, etc.)
• Mechanistic insights supporting preferential and/or early use of one or more CT and/or CET, suggesting synergy or reduced efficacy of treatments in light of previous or concurrent use of CT and/or CET
• Shared determinants of efficacy, toxicity and/or resistance across CT and/or CET, both at the clinical or biological level
• Comparison of efficacy and/or toxicity of CT and/or CET in the same clinical setting (prospective or retrospective studies, narrative or systematic reviews with or without metanalyses, etc.)

Please note: manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) will not be accepted in any of the sections of Frontiers in Oncology.

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This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
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Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: lymphoid neoplasm, CAR-T cell therapies, bispecific antibodies, cellular therapies, CAR-T cells, B-ALL, lymphoma, multiple myeloma, Allogeneic CAR Or NK CAR, allogeneic transplantation

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.