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Despite the prominence of complex psychosocial problems in aging clients, geriatric case management has generally emphasized the provision of concrete resources and services as its primary function. However, some of the literature as well as the findings of this study, point to competent case management as being contingent on interventions that successfully address key psychosocial problems. This paper presents a qualitative study involving experienced geriatric care managers. Psychosocial problem and intervention categories are identified as well as overarching themes with significant implications for practice. The paper argues that a grounded, thorough, well-explicated and generalizable model for clinically-focused geriatric case management practice is necessary; it also suggests additional research towards the development of such a model. [ABSTRACT FROM AUTHOR]

This article builds on prior analyses of data collected from a qualitative study of 50 pairs of social worker-physician collaborators in. This article presents the elements of a typology of collaborators from both professions developed from those analyses. The typology was also applied to the entire sample and each respondent characterized according to type (traditional, transitional or transformational). Further analysis was done to evaluate the relationships between type and collaborative perspectives. The sample was primarily transitional (56%-58%) and there were more traditional social workers (22%) and transformational doctors (24%) than anticipated. Social workers, as a group, were much less satisfied with the doctors than the doctors were with them although both groups of traditional respondents were the most dissatisfied. Both groups were least transformational in relation to control over decision making. [ABSTRACT FROM AUTHOR]

In past reviews of the literature on psychosocial interventions for cancer patients, different reviewers have reached disparate conclusions about the ability of a psychosocial intervention to have an impact on cancer survival. This article highlights some of the basis for differences of opinion, including the range of psychosocial interventions provided to patients and the challenges inherent in conducting research studies of this type. Social workers who work with cancer patients at vulnerable times need to understand what the current evidence shows can be gained from participation in a psychosocial intervention. Several key questions have been identified that can provide the basis for future rigorous studies. The role of the social worker in participating and shaping research on the relationship of psychosocial intervention and cancer survival is also discussed. [ABSTRACT FROM AUTHOR]

As health care is being restructured, health care institutions are recognizing that interdisciplinary collaboration is an essential element of both effective patient care and organizational survival. This paper analyzes self-reported views of actual collaborative activities between 50 pairs of social workers and physicians on a specific shared case in an acute care hospital setting. Through examining the degree of congruence in perspectives of each pair of collaborators, we compare the two professions' views of the collaborative process and outcome. Additionally, each profession's outlook on its own and the other profession's roles and responsibilities in the case is examined.Our findings indicate that many social work and physician collaborators share similar perspectives about many aspects of their joint patient care endeavors. Where there was disagreement within a pair, almost always, it was a social worker selecting or discussing a variable when her physician counterpart did not. Physicians were less likely than their social work counterparts to identify patient/family problems related to adjustment to illness and problems connected to hospital and community resources as well.Social workers were much less satisfied with the collaboration, saw many more things that they or their collaborator could have done differently and even perceived more disagreement about the approach to the case than did their physician collaborators. It is important to understand, empirically, the dynamics of successful collaboration and to assist social workers in becoming influential and effective collaborators with other health professionals. [ABSTRACT FROM AUTHOR]

Interdisciplinary collaboration is becoming increasingly important as the current complexity and cost of health care require an efficient and well-coordinated service delivery system. To unerstand the factors contributing to positive and negative collaboration, 53 social workers and 50 physicians in 12 hospital settings were interviewed about their best and worst experiences collaborating on a case. Thirty precoded items were classified into three constructs that reflect aspects of collaboration related to the case, to interaction between collaborators, and to the competence of the collaborator. Differences between the two professions were greatest on the interactional factors, with social workers valuing them much more than physicians did. Communication appeared to be the only intrinsic or universal aspect of collaboration equally important to both groups in both types of cases. Implications for social work practice and leadership are discussed. [ABSTRACT FROM AUTHOR]

Background: TP53-mutant mantle cell lymphoma (MCL) is associated with poor survival outcomes with standard chemoimmunotherapy. Dual BTK and BCL2-inhibition with or without anti-CD20 monoclonal antibody therapy has shown promising activity in TP53-mutant MCL. We conducted a multi-center phase 2 study of zanubrutinib, obinutuzumab, and venetoclax (BOVen) in untreated MCL patients with TP53 mutation. Patients initially received zanubrutinib 160mg twice daily and obinutuzumab. Obinutuzumab 1000mg was given on cycle 1 day 1, 8, 15 and day 1 of cycles 2-8. After 2 cycles, venetoclax was added with weekly dose-ramp up to 400mg daily. After 24 cycles, if patients were in complete remission with undetectable minimal residual disease using an immunosequencing assay, treatment was discontinued. The primary endpoint was met if ³11 patients were progression free at 2 years. The study included 25 patients with untreated MCL with TP53 mutation. The best overall response rate was 96% (24/25) and the complete response rate was 88% (22/25). Frequency of uMRD5 and uMRD6 at cycle 13 was 95% (18/19) and 84% (16/19). With median follow up of 28.2 months, the primary endpoint was met with a 2-year progression-free survival of 72%, and the 2-year disease-specific and overall survival were 91% and 76%, respectively. Common side effects were generally low grade and included diarrhea (64%), neutropenia (32%), and infusion-related reactions (24%). BOVen was well tolerated and met its primary efficacy endpoint in TP53-mutant mantle cell lymphoma. These data support its use and further evaluation of the BOVen regimen in this high-risk population. NCT03824483., (Copyright © 2024 American Society of Hematology.)

Double-hit lymphoma (DHL) is a high-risk subtype of large B-cell lymphoma, defined by concurrent rearrangements MYC and BCL2 . The diagnosis is confirmed through histologic and immunophenotypic examination and fluorescence in situ hybridization (FISH) to demonstrate the rearrangements. DHL morphology ranges from DLBCL to high-grade B-cell lymphoma which can resemble Burkitt lymphoma and is almost always germinal center B-cell like (GCB). Prognosis is influenced by elevated lactate dehydrogenase (LDH), advanced stage, and extranodal involvement, among other factors. Treatment outcomes vary, but intensive chemotherapy regimens such as dose-adjusted EPOCH-R have shown the most promising results, though low-risk cases do occur and may do well with less intensive treatments. Recent therapeutic advances such as CAR-T cells and bispecific antibodies offer promise for patients with relapsed/refractory disease. This review synthesizes data from recent literature to provide a comprehensive analysis of the molecular underpinnings, diagnostic criteria, prognostic factors, and therapeutic strategies for DHL.

Abstract: T-cell engaging-therapies have transformed the treatment landscape of relapsed and refractory B-cell non-Hodgkin lymphomas by offering highly effective treatments for patients with historically limited therapeutic options. This review focuses on the advances in chimeric antigen receptor-modified T cells and bispecific antibodies, first providing an overview of each product type, followed by exploring the primary data for currently available products in large B-cell lymphoma, follicular lymphoma, and mantle cell lymphoma. This review also highlights key logistical and sequencing considerations across diseases and product types that can affect clinical decision-making., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

The ECHELON-1 trial demonstrated the effectiveness of brentuximab vedotin (BV) in combination with doxorubicin, vinblastine, and dacarbazine as a frontline treatment regimen in classical Hodgkin lymphoma. However, peripheral neuropathy (PN) is common with this regimen, occurring in up to two-thirds of patients. While standard prescribing information recommends BV dose modification at the onset of grade 2 PN, management strategies for PN are not well-defined. Most commonly, clinicians dose reduce or discontinue BV, vinblastine, or both. We review evidence-based and practical approaches for managing peripheral neuropathy, emphasizing early detection and dose modification., Competing Interests: Declaration of Competing Interest Jeremy Abramson declares support for the present manuscript (no payments made)– Seagen; grants or contracts from any entity – Seagen, Merck, Mustang Bio, Cellectis, Bristol Myers Squibb, Genentech/Roche; consulting fees – Bristol Myers Squibb, AstraZeneca, AbbVie, Genentech/Roche, Kite Pharma/Gilead, Seagen, Interius, BeiGene, Cellectar, Lilly, Incyte, Caribou Biosciences, Takeda, Janssen, Epizyme, Century Therapeutics, MorphoSys, Mustang Bio, Ono Pharma, Kymera; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events – Genmab, Bristol Myers Squibb, AstraZeneca, Regeneron, AbbVie. Robert Stuver declares no conflicts related to this manuscript. Alex Herrera declares grants or contracts from any entity – Bristol Myers Squibb, Genentech, Merck, Seagen, AstraZeneca, Karyopharm, Kite Pharma, Gilead Sciences, AstraZeneca, ADC Therapeutics; consulting fees – Bristol Myers Squibb, Genentech, Merck, Seagen, AstraZeneca, Karyopharm, ADC Therapeutics, Takeda, Tubulis, Regeneron, Genmab, Pfizer, Caribou Biosciences, Adicet Bio, AbbVie, Allogene. Emily Patterson declares no conflicts related to this manuscript. Yi-Ping Wen declares no conflicts related to this manuscript. Alison Moskowitz declares grants or contracts from any entity – Leukemia Lymphoma Society – Career Development Program, Incyte, Merck, Secura Bio, Bristol Myers Squibb, Syndax, Seagen, Genentech, Kite Pharma, Gilead Sciences, AstraZeneca, ADC Therapeutics; consulting fees – Bristol Myers Squibb, Genentech, Merck, Seagen, AstraZeneca, ADC Therapeutics, Takeda, Genmab, Pfizer, Caribou Biosciences, Adicet Bio, AbbVie, Allogene Therapeutics; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events – Affimed, Bio Ascend, Canadian Heme Conference, Janpix, Physician Education Resource, Academic Medical Education, BP, Great Debates & Updates, Harborside Press, Imbrium Therapeutics, International Symposium on Hodgkin Lymphoma, Kyowa Hakko Pharma, Medscape, Merck Sharp & Bohue, Ahompr, Seagen, Takeda, Tessa, Triangle Insights Group, UpToDate, WebMD; participation on a data safety monitoring board or advisory board – Affimed, Janpix, Seagen, Kyowa Hakko Pharma., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Deficient (d) DNA mismatch repair (MMR) is a biomarker predictive of better response to PD-1 blockade immunotherapy in solid tumors. dMMR can be caused by mutations in MMR genes or by protein inactivation, which can be detected by sequencing and immunohistochemistry, respectively. To investigate the role of dMMR in diffuse large B-cell lymphoma (DLBCL), MMR gene mutations and expression of MSH6, MSH2, MLH1, and PMS2 proteins were evaluated by targeted next-generation sequencing and immunohistochemistry in a large cohort of DLBCL patients treated with standard chemoimmunotherapy, and correlated with the tumor immune microenvironment characteristics quantified by fluorescent multiplex immunohistochemistry and gene-expression profiling. The results showed that genetic dMMR was infrequent in DLBCL and was significantly associated with increased cancer gene mutations and favorable immune microenvironment, but not prognostic impact. Phenotypic dMMR was also infrequent, and MMR proteins were commonly expressed in DLBCL. However, intratumor heterogeneity existed, and increased DLBCL cells with phenotypic dMMR correlated with significantly increased T cells and PD-1 + T cells, higher average nearest neighbor distance between T cells and PAX5 + cells, upregulated immune gene signatures, LE4 and LE7 ecotypes and their underlying Ecotyper-defined cell states, suggesting the possibility that increased T cells targeted only tumor cell subsets with dMMR. Only in patients with MYC¯ DLBCL, high MSH6/PMS2 expression showed significant adverse prognostic effects. This study shows the immunologic and prognostic effects of genetic/phenotypic dMMR in DLBCL, and raises a question on whether DLBCL-infiltrating PD-1 + T cells target only tumor subclones, relevant for the efficacy of PD-1 blockade immunotherapy in DLBCL., Competing Interests: D.O., Q.A., and H.N. are employees of NeoGenomics Laboratories, Inc. The NeoGenomics Laboratories, Inc. had no role in the design of the study, in the writing of the manuscript, or in the decision to publish the results., (© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.)

An unmet need exists for patients with relapsed/refractory (R/R) follicular lymphoma (FL) and high-risk disease features, such as progression of disease within 24 months (POD24) from first-line immunochemotherapy or disease refractory to both CD20-targeting agent and alkylator (double refractory), due to no established standard of care and poor outcomes. Chimeric antigen receptor (CAR) T cell therapy is an option in R/R FL after two or more lines of prior systemic therapy, but there is no consensus on its optimal timing in the disease course of FL, and there are no data in second-line (2L) treatment of patients with high-risk features. Lisocabtagene maraleucel (liso-cel) is an autologous, CD19-directed, 4-1BB CAR T cell product. The phase 2 TRANSCEND FL study evaluated liso-cel in patients with R/R FL, including 2L patients who all had POD24 from diagnosis after treatment with anti-CD20 antibody and alkylator ≤6 months of FL diagnosis and/or met modified Groupe d'Etude des Lymphomes Folliculaires criteria. Primary/key secondary endpoints were independent review committee-assessed overall response rate (ORR)/complete response (CR) rate. At data cutoff, 130 patients had received liso-cel (median follow-up, 18.9 months). Primary/key secondary endpoints were met. In third-line or later FL (n = 101), ORR was 97% (95% confidence interval (CI): 91.6‒99.4), and CR rate was 94% (95% CI: 87.5‒97.8). In 2L FL (n = 23), ORR was 96% (95% CI: 78.1‒99.9); all responders achieved CR. Cytokine release syndrome occurred in 58% of patients (grade ≥3, 1%); neurological events occurred in 15% of patients (grade ≥3, 2%). Liso-cel demonstrated efficacy and safety in patients with R/R FL, including high-risk 2L FL. ClinicalTrials.gov identifier: NCT04245839 ., (© 2024. The Author(s).)

STOP-CA was a multicenter, double-blind, randomized, placebo-controlled trial comparing atorvastatin to placebo in treatment-naïve lymphoma patients receiving anthracycline-based chemotherapy. We performed a preplanned subgroup to analyze the impact of atorvastatin on efficacy in patients with diffuse large B-cell lymphoma (DLBCL). Patients received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) at standard doses for six 21-day cycles and were randomly assigned to receive atorvastatin 40 mg daily ( n  = 55) or placebo ( n  = 47) for 12 months. The complete response (CR) rate was numerically higher in the atorvastatin arm (95% [52/55] vs. 85% [40/47], p  = .18), but this was not statistically significant. Adverse event rates were similar between the atorvastatin and placebo arms. In summary, atorvastatin did not result in a statistically significant improvement in the CR rate or progression-free survival, but both were numerically improved in the atorvastatin arm. These data warrant further investigation into the potential therapeutic role of atorvastatin added to anthracycline-based chemotherapies.

Inhibition of Bruton's tyrosine kinase (BTK) through covalent modifications of its active site (e.g., ibrutinib [IBT]) is a preferred treatment for multiple B cell malignancies. However, IBT-treated patients are more susceptible to invasive fungal infections, although the mechanism is poorly understood. Neutrophils are the primary line of defense against these infections; therefore, we examined the effect of IBT on primary human neutrophil effector activity against Aspergillus fumigatus. IBT significantly impaired the ability of neutrophils to kill A. fumigatus and potently inhibited reactive oxygen species (ROS) production, chemotaxis, and phagocytosis. Importantly, exogenous TNF-α fully compensated for defects imposed by IBT and newer-generation BTK inhibitors and restored the ability of neutrophils to contain A. fumigatus hyphal growth. Blocking TNF-α did not affect ROS production in healthy neutrophils but prevented exogenous TNF-α from rescuing the phenotype of IBT-treated neutrophils. The restorative capacity of TNF-α was independent of transcription. Moreover, the addition of TNF-α immediately rescued ROS production in IBT-treated neutrophils, indicating that TNF-α worked through a BTK-independent signaling pathway. Finally, TNF-α restored effector activity of primary neutrophils from patients on IBT therapy. Altogether, our data indicate that TNF-α rescued the antifungal immunity block imposed by inhibition of BTK in primary human neutrophils.

Venetoclax-obinutuzumab (Ven-O) is frequently administered off-label in relapsed/refractory (r/r) CLL/SLL where venetoclax-rituximab is the approved regimen. We conducted this retrospective, real-world study to evaluate Ven-O in r/r CLL/SLL. Between 7/2019 and 6/2022, 40 patients with r/r CLL/SLL on Ven-O were included. The median age was 72, 28.2% had TP53 mutation and/or 17p deletion, median number of prior therapies was 1 (range, 1-6), and 55% had prior BTK inhibitor exposure. The overall response rate was 90% (complete response [CR] or CR with incomplete marrow recovery in 27.5% and partial response in 62.5%) of patients, and the 2-year progression-free survival was 81.2% (95% CI, 69.5-94.8). Therapy was well tolerated. No laboratory or clinical TLS occurred with venetoclax (Howard criteria). One (3%) patient experienced laboratory TLS with obinutuzumab initiation. In summary, this retrospective cohort study demonstrated that Ven-O achieves frequent, durable responses and can be safely administered in r/r CLL/SLL.

Abstract: Bispecific antibodies (BsAb) that target CD3 and CD20 represent a new milestone in the treatment of patients with B-cell non-Hodgkin lymphoma. These drugs have demonstrated remarkable single-agent activity in patients with heavily pretreated disease, and 3 drugs have so far received regulatory approvals in various countries. However, BsAbs can potentially lead to severe toxicity associated with T-cell activation, particularly cytokine release syndrome (CRS). The anticipated widespread use of these off-the-shelf products poses challenges for implementation and highlights the need for guidance in anticipating, mitigating, and managing adverse events. In clinical trials, guidance for the evaluation and treatment of CRS and neurotoxicity associated with BsAb therapy has been modeled after algorithms originally created for chimeric antigen receptor (CAR) T-cell therapies and other immune effector therapies, yet notable differences in timing, quality, and severity exist between the toxicities of BsAbs and CAR T-cell therapies. We therefore convened an international panel of academic and community practice physicians, advanced practitioners, registered nurses, and pharmacists with experience using CD3×CD20 BsAbs in clinical trial and off-trial settings to provide comprehensive, consensus-based recommendations specific to the assessment and management of CD3×CD20 BsAb-related toxicities., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Abstract: A041202 (NCT01886872) is a phase 3 study comparing bendamustine plus rituximab (BR) with ibrutinib and the combination of ibrutinib plus rituximab (IR) in previously untreated older patients with chronic lymphocytic leukemia (CLL). The initial results showed that ibrutinib-containing regimens had superior progression-free survival (PFS) and rituximab did not add additional benefits. Here we present an updated analysis. With a median follow-up of 55 months, the median PFS was 44 months (95% confidence interval [CI], 38-54) for BR and not yet reached in either ibrutinib-containing arm. The 48-month PFS estimates were 47%, 76%, and 76% for BR, ibrutinib, and IR, respectively. The benefit of ibrutinib regimens over chemoimmunotherapy was consistent across subgroups of patients defined by TP53 abnormalities, del(11q), complex karyotype, and immunoglobulin heavy chain variable region (IGHV). No significant interaction effects were observed between the treatment arm and del(11q), the complex karyotype, or IGHV. However, a greater difference in PFS was observed among the patients with TP53 abnormalities. There was no difference in the overall survival. Notable adverse events with ibrutinib included atrial fibrillation (afib) and hypertension. Afib was observed in 11 patients (pts) on BR (3%) and 67 pts on ibrutinib (18%). All-grade hypertension was observed in 95 pts on BR (27%) and 263 pts on ibrutinib (55%). These data show that ibrutinib regimens prolong PFS compared with BR for older patients with treatment-naïve CLL. These benefits were observed across subgroups, including high-risk groups. Strikingly, within the ibrutinib arms, there was no inferior PFS for patients with abnormalities in TP53, the highest risk feature observed in CLL. These data continue to demonstrate the efficacy of ibrutinib in treatment-naïve CLL.

Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are essentially different manifestations of the same disease that are similarly managed. A number of molecular and cytogenetic variables with prognostic implications have been identified. Undetectable minimal residual disease at the end of treatment with chemoimmunotherapy or venetoclax-based combination regimens is an independent predictor of improved survival among patients with previously untreated or relapsed/refractory CLL/SLL. The selection of treatment is based on the disease stage, presence or absence of del(17p) or TP53 mutation, immunoglobulin heavy chain variable region mutation status, patient age, performance status, comorbid conditions, and the agent's toxicity profile. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with CLL/SLL.

Purpose: To report the primary analysis results from the mantle cell lymphoma (MCL) cohort of the phase I seamless design TRANSCEND NHL 001 (ClinicalTrials.gov identifier: NCT02631044) study., Methods: Patients with relapsed/refractory (R/R) MCL after ≥two lines of previous therapy, including a Bruton tyrosine kinase inhibitor (BTKi), an alkylating agent, and a CD20-targeted agent, received lisocabtagene maraleucel (liso-cel) at a target dose level (DL) of 50 × 10 6 (DL1) or 100 × 10 6 (DL2) chimeric antigen receptor-positive T cells. Primary end points were adverse events (AEs), dose-limiting toxicities, and objective response rate (ORR) by independent review committee per Lugano criteria., Results: Of 104 leukapheresed patients, liso-cel was infused into 88. Median (range) number of previous lines of therapy was three (1-11) with 30% receiving ≥five previous lines of therapy, 73% of patients were age 65 years and older, 69% had refractory disease, 53% had BTKi refractory disease, 23% had TP53 mutation, and 8% had secondary CNS lymphoma. Median (range) on-study follow-up was 16.1 months (0.4-60.5). In the efficacy set (n = 83; DL1 + DL2), ORR was 83.1% (95% CI, 73.3 to 90.5) and complete response (CR) rate was 72.3% (95% CI, 61.4 to 81.6). Median duration of response was 15.7 months (95% CI, 6.2 to 24.0) and progression-free survival was 15.3 months (95% CI, 6.6 to 24.9). Most common grade ≥3 treatment-emergent AEs were neutropenia (56%), anemia (37.5%), and thrombocytopenia (25%). Cytokine release syndrome (CRS) was reported in 61% of patients (grade 3/4, 1%; grade 5, 0), neurologic events (NEs) in 31% (grade 3/4, 9%; grade 5, 0), grade ≥3 infections in 15%, and prolonged cytopenia in 40%., Conclusion: Liso-cel demonstrated high CR rate and deep, durable responses with low incidence of grade ≥3 CRS, NE, and infections in patients with heavily pretreated R/R MCL, including those with high-risk, aggressive disease.

Abstract: We previously reported high rates of undetectable minimal residual disease <10-4 (uMRD4) with ibrutinib plus fludarabine, cyclophosphamide, and rituximab (iFCR) followed by 2-year ibrutinib maintenance (I-M) in treatment-naïve chronic lymphocytic leukemia (CLL). Here, we report updated data from this phase 2 study with a median follow-up of 63 months. Of 85 patients enrolled, including 5 (6%) with deletion 17p or TP53 mutation, 91% completed iFCR and 2-year I-M. Five-year progression-free survival (PFS) and overall survival were 94% (95% confidence interval [CI], 89%-100%) and 99% (95% CI, 96%-100%), respectively. No additional deaths have occurred with this extended follow-up. No difference in PFS was observed by immunoglobulin heavy-chain variable region gene status or duration of I-M. High rates of peripheral blood (PB) uMRD4 were maintained (72% at the end of iFCR, 66% at the end of 2-year I-M, and 44% at 4.5 years from treatment initiation). Thirteen patients developed MRD conversion without clinical progression, mostly (77%) after stopping ibrutinib. None had Bruton tyrosine kinase (BTK) mutations. One patient had PLCG2 mutation. Six of these patients underwent ibrutinib retreatment per protocol. Median time on ibrutinib retreatment was 34 months. The cumulative incidence of atrial fibrillation was 8%. Second malignancy or nonmalignant hematologic disease occurred in 13%, mostly nonmelanoma skin cancer. Overall, iFCR with 2-year I-M achieved durably deep responses in patients with diverse CLL genetic markers. Re-emergent clones lacked BTK mutation and retained sensitivity to ibrutinib upon retreatment. This trial is registered at www.clinicaltrials.gov as #NCT02251548., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Abstract: Lisocabtagene maraleucel (liso-cel) demonstrated significant efficacy with a manageable safety profile as third-line or later treatment for patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) in the TRANSCEND NHL 001 study. Primary end points were adverse events (AEs), dose-limiting toxicities, and objective response rate (ORR) per independent review committee. Key secondary end points were complete response (CR) rate, duration of response (DOR), progression-free survival (PFS), and overall survival (OS). After 2-year follow-up, patients could enroll in a separate study assessing long-term (≤15 years) safety and OS. Liso-cel-treated patients (N = 270) had a median age of 63 years (range, 18-86 years) and a median of 3 prior lines (range, 1-8) of systemic therapy, and 181 of them (67%) had chemotherapy-refractory LBCL. Median follow-up was 19.9 months. In efficacy-evaluable patients (N = 257), the ORR was 73% and CR rate was 53%. The median (95% confidence interval) DOR, PFS, and OS were 23.1 (8.6 to not reached), 6.8 (3.3-12.7), and 27.3 months (16.2-45.6), respectively. Estimated 2-year DOR, PFS, and OS rates were 49.5%, 40.6%, and 50.5%, respectively. In the 90-day treatment-emergent period (N = 270), grade 3 to 4 cytokine release syndrome and neurological events occurred in 2% and 10% of patients, respectively. The most common grade ≥3 AEs in treatment-emergent and posttreatment-emergent periods, respectively, were neutropenia (60% and 7%) and anemia (37% and 6%). Liso-cel demonstrated durable remissions and a manageable safety profile with no new safety signals during the 2-year follow-up in patients with R/R LBCL. These trials were registered at www.ClinicalTrials.gov as #NCT02631044 and #NCT03435796., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Abstract: Lisocabtagene maraleucel (liso-cel), a chimeric antigen receptor (CAR) T-cell therapy, received the US Food and Drug Administration approval in 2022 for second-line treatment of diffuse large B-cell lymphoma (DLBCL) for patients with refractory disease or early relapse after first-line chemoimmunotherapy. This decision was based on the TRANSFORM study demonstrating improvements in event-free survival with liso-cel compared with standard care. Given the high costs of CAR T-cell therapies, particularly as they transition to second-line treatment, a cost-effectiveness analysis is essential to determine their economic viability. The study used a partitioned survival model with standard parametric functions to evaluate the cost-effectiveness of liso-cel aganist platinum-based chemotherapy followed by high-dose chemotherapy and autologous hematopoietic stem cell transplantation over a lifetime horizon The analysis relied on data from the TRANSFORM and TRANSCEND trials, established literature, and public data sets to calculate the incremental cost-effectiveness ratio (ICER). For a representative cohort of US adults aged 60 years, ICER of liso-cel was $99 669 per quality-adjusted life-year (QALY) from a health care sector perspective and $68 212 per QALY from a societal perspective, confirming its cost-effectiveness at the $100 000 per QALY threshold. Nonetheless, under certain scenarios, liso-cel surpasses this benchmark but remains within the US acceptable range of $150 000 per QALY. A key finding underlines the importance of incorporating productivity losses into such analyses to capture the broader societal values of novel therapies. Although these therapies offer substantial clinical benefits, their high acquisition costs and limited long-term data critically challenge their economic sustainability., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

CD19-targeted chimeric antigen receptor (CAR) T-cell therapy has revolutionized treatment for patients with relapsed/refractory large B-cell lymphoma (LBCL). However, data available concerning the impact of the prognostic value of quantitative 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET/CT) parameters on the CAR T-related outcomes and toxicities are limited. Therefore, we aimed to evaluate the predictive value of pre- and post-CAR T metabolic parameters on survival and toxicities following CAR T-cell therapy. Fifty-nine patients with PET/CT scans done pre-and post-CAR T infusion were retrospectively identified and analyzed in a single institution database of LBCL patients treated with commercial CD19-targeted CAR T-cell therapy. The median follow-up was 10.7 months [interquartile range (IQR): 2.6-25.5 months]. The overall response (complete response-CR and partial response) and CR rates post-CAR T were 76% (n = 45) and 53% (n = 31), respectively. On univariate analysis, low pre-CAR T total lesion glycolysis (TLG) and metabolic tumor volume (MTV) predicted improved overall response post-CAR T (OR = 4.7, p = 0.01, OR = 9.5, p = 0.03, respectively) and CR post-CAR T (OR = 12.4, p = 0.0004, OR = 10.9, p = 0.0001, respectively). High TLG pre-CAR T was correlated with cytokine release syndrome (CRS, OR = 3.25, p = 0.04). High MTV pre-CAR T was correlated with developing immune effector cell neurotoxicity syndrome (ICANS) events (OR = 4.3, p = 0.01), and high SUV pre-CAR T was associated with grade 3-4 neurological events (OR = 12, p = 0.01). High MTV/TLG/SUVmax post-CAR T were significantly associated with inferior Overall survival (OS). On multivariate analysis, high TLG pre-CAR T (HR = 2.4, p = 0.03), age ≥60 (HR = 2.7, p = 0.03), and bulky disease (≥5 cm) at the time of apheresis (HR = 2.5, p = 0.02) were identified to be independent prognostic factors for inferior PFS. High MTV post-CAR T was identified as the most prognostic factor associated with inferior OS., (© 2023 John Wiley & Sons Ltd.)

Abstract: In this real-world evaluation of tafasitamab-lenalidomide (TL) in relapsed or refractory LBCL, patients receiving TL had higher rates of comorbidities and high-risk disease characteristics, and substantially lower progression-free survival and overall survival, compared with the L-MIND registration clinical trial for TL., (© 2023 by The American Society of Hematology.)

Maintenance rituximab in mantle cell lymphoma (MCL) has improved survival and supports exploration of maintenance with novel agents. We evaluated the safety and efficacy of ibrutinib maintenance (I-M) after induction in patients with treatment-naive MCL. Patients with MCL with complete response (CR) or partial response to frontline chemoimmunotherapy ± autologous stem cell transplantation (auto-SCT) received I-M 560 mg daily for up to 4 years. Primary objective was 3-year progression-free survival (PFS) rate from initiation of I-M. Minimal residual disease (MRD) assessments by next-generation sequencing (NGS) on peripheral blood were measured before I-M initiation and at 1, 6, and 18 to 24 months after initiation. Among 36 patients, the median age was 60 years (range, 46-90). For frontline treatment, 18 patients (50%) had consolidation with auto-SCT in CR1 before I-M. At median follow-up of 55.7 months, 17 patients (47%) completed full course I-M (median, 37.5 cycles; range, 2-52). The 3-year PFS and overall survival (OS) rates were 94% and 97%, respectively. With prior auto-SCT, 3-year PFS and OS rates were both 100%. The most common treatment-related adverse event with I-M was infection (n = 31; 86%), typically low grade; the most common grade 3/4 toxicities were hematologic. In 22 patients with MRD assessments, all were MRD negative after induction. Six became MRD positive on I-M, with 2 reverting to MRD-negative status with continued I-M, and all maintain radiographic CR with the exception of 1 with disease progression. I-M is feasible in MCL after frontline chemoimmunotherapy with manageable toxicities although significant. Changes in NGS-MRD were noted in limited patients during maintenance with few progression and survival events. This trial was registered at www.clinicaltrials.gov as #NCT02242097., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: Chimeric antigen receptor (CAR) T-cells targeting CD19 have been established as a leading engineered T-cell therapy for B-cell lymphomas; however, data for patients with central nervous system (CNS) involvement are limited., Methods: We retrospectively report on CNS-specific toxicities, management, and CNS response of 45 consecutive CAR T-cell transfusions for patients with active CNS lymphoma at the Massachusetts General Hospital over a 5-year period., Results: Our cohort includes 17 patients with primary CNS lymphoma (PCNSL; 1 patient with 2 CAR T-cell transfusions) and 27 patients with secondary CNS lymphoma (SCNSL). Mild ICANS (grade 1-2) was observed after 19/45 transfusions (42.2%) and severe immune effector cell-associated neurotoxicity syndrome (ICANS) (grade 3-4) after 7/45 transfusions (15.6%). A larger increase in C-reactive protein (CRP) levels and higher rates of ICANS were detected in SCNSL. Early fever and baseline C-reactive protein levels were associated with ICANS occurrence. CNS response was seen in 31 cases (68.9%), including a complete response of CNS disease in 18 cases (40.0%) which lasted for a median of 11.4 ± 4.5 months. Dexamethasone dose at time of lymphodepletion (but not at or after CAR T-cell transfusion) was associated with an increased risk for CNS progression (hazard ratios [HR] per mg/d: 1.16, P = .031). If bridging therapy was warranted, the use of ibrutinib translated into favorable CNS-progression-free survival (5 vs. 1 month, HR 0.28, CI 0.1-0.7; P = .010)., Conclusions: CAR T-cells exhibit promising antitumor effects and a favorable safety profile in CNS lymphoma. Further evaluation of the role of bridging regimens and corticosteroids is warranted., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

BTK inhibitors (BTKi) are highly effective in B-cell malignancies. Acalabrutinib and zanubrutinib have exhibited favorable safety profiles when compared with ibrutinib. We identified all published/presented randomized trials comparing a second-generation BTKi with ibrutinib and reconstructed individual patient-level, censored time-to-event data for adverse events to evaluate the impact of second-generation BTKi on safety outcomes including atrial fibrillation/flutter [AF], hypertension, bleeding, diarrhea, and infection. 1386 pts from ELEVATE-RR ( n  = 533), ALPINE ( n  = 652), and ASPEN ( n  = 201) trials were included in the analyses. Acalabrutinib or zanubrutinib were associated with significant reductions in cumulative event rates of AF (HR 0.28, 95% CI 0.18-0.42, p  < 0.001), bleeding (HR 0.65, 95% CI 0.52-0.81, p  < 0.001), diarrhea (HR 0.61, 95% CI 0.47-0.78, p  < 0.001), hypertension (HR 0.40, 95% CI 0.27-0.61, p  < 0.001), and infections (HR 0.83, 95% CI 0.70-0.98, p  = 0.032). In summary, zanubrutinib and acalabrutinib have a favorable safety profile among pts with r/r B-cell malignancies. These data support use of acalabrutinib or zanubrutinib as preferred BTK inhibitors for approved indications.

Despite the success of CD19-targeted chimeric antigen receptor (CAR T)-cell therapy in patients with relapsed/refractory large B-cell lymphoma (LBCL), there is a need for effective salvage strategies post-CAR T-cell therapy failure. We conducted a multi-institutional retrospective study of patients who relapsed following CAR T-cell therapy (axicabtagene ciloleucel [axi-cel] or tisagenlecleucel [tisa-cel]) and received salvage therapies (radiation therapy [RT] alone, systemic therapy alone, or combined modality therapy [CMT]). A total of 120 patients with post-CAR T relapsed LBCL received salvage therapies (RT alone, 25 patients; CMT, 15 patients; systemic therapy alone, 80 patients). The median follow-up from CAR T-cell infusion was 10.2 months (interquartile range, 5.2-20.9 months). Failure occurred in previously involved sites prior to CAR T-cell therapy in 78% of patients (n=93). A total of 93 sites were irradiated in 54 patients who received any salvage RT post-CAR T failure. The median dose/fractionation were 30 Gy (range, 4-50.4 Gy) and 10 fractions (range, 1-28 fractions). The 1-year local control rate for the 81 assessable sites was 84%. On univariate analysis, the median overall survival (OS) from the start date of RT was significantly higher among patients who received comprehensive RT versus focal RT (19.1 months vs. 3.0 months; P=<0.001). Twenty-three of 29 patients who received comprehensive RT had limited-stage disease. Among these, there was no difference in median OS among the patients who received RT alone versus those who received RT followed by additional therapies (log-rank P=0.2). On multivariate survival analysis, achieving PR or CR post-CAR T (hazard ratio =0.5; 95% confidence interval: 0.3-0.9; P=0.01) was independently associated with superior OS. Our findings suggest that RT can provide local control for LBCL relapsed post-CAR T-cell therapy, particularly in patients with limited-stage relapsed disease treated with comprehensive RT.

Novel targeted therapies (small molecule inhibitors, antibody-drug conjugates, and CD19-directed therapies) have changed the treatment landscape of relapsed/refractory B-cell lymphomas. Bruton's tyrosine kinase (BTK) inhibitors continue to evolve in the management of mantle cell lymphoma (MCL), in both the relapsed/refractory and the frontline setting. Anti-CD19 CAR T-cell therapies are now effective and approved treatment options for relapsed/refractory follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and MCL. Bispecific T-cell engagers represent a novel immunotherapeutic approach for relapsed FL and DLBCL after multiple lines of therapies, including prior CAR T-cell therapy. These NCCN Guideline Insights highlight the significant updates to the NCCN Guidelines for B-Cell Lymphomas for the treatment of FL, DLBCL, and MCL.

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin's lymphoma worldwide and particularly in Africa, where the incidence of HIV is the highest in the world. R-CHOP is the standard of care regimen for DLBCL, but access to rituximab is limited in developing countries., Methods: This is a retrospective cohort study that included all HIV-negative patients with DLBCL who received R-CHOP at a single institution from January 2012 to December 2017. Clinical and demographic data were collected to assess factors that influenced survival., Results: Seventy-three patients were included. Median age was 55 (17-76), 67.1% of patients were younger than 60 years, and 60.3% were female. Most presented with stages III/IV disease (53.5%) but with good performance status (56.% PS 0 and 1). Progression-free survival at 3 and 5 years was 75% and 69%, and overall survival at 3 and 5 years was 77% and 74%, respectively. Median survival had not been reached with a median follow-up of 3.5 years(0.13-7.9). Overall survival was significantly affected by performance status (P = .04), but not by IPI or age. Survival was significantly associated with response to chemotherapy after 4-5 cycles of R-CHOP (P = 0.005)., Conclusions: Treatment of DLBCL with R-CHOP is feasible and can achieve good outcomes in resource-limited settings with rituximab-based chemotherapy. Poor performance status was the most important adverse prognostic factor in this cohort of HIV-negative patients., (© The Author(s) 2023. Published by Oxford University Press.)

Importance: Anthracyclines treat a broad range of cancers. Basic and retrospective clinical data have suggested that use of atorvastatin may be associated with a reduction in cardiac dysfunction due to anthracycline use., Objective: To test whether atorvastatin is associated with a reduction in the proportion of patients with lymphoma receiving anthracyclines who develop cardiac dysfunction., Design, Setting, and Participants: Double-blind randomized clinical trial conducted at 9 academic medical centers in the US and Canada among 300 patients with lymphoma who were scheduled to receive anthracycline-based chemotherapy. Enrollment occurred between January 25, 2017, and September 10, 2021, with final follow-up on October 10, 2022., Interventions: Participants were randomized to receive atorvastatin, 40 mg/d (n = 150), or placebo (n = 150) for 12 months., Main Outcomes and Measures: The primary outcome was the proportion of participants with an absolute decline in left ventricular ejection fraction (LVEF) of ≥10% from prior to chemotherapy to a final value of <55% over 12 months. A secondary outcome was the proportion of participants with an absolute decline in LVEF of ≥5% from prior to chemotherapy to a final value of <55% over 12 months., Results: Of the 300 participants randomized (mean age, 50 [SD, 17] years; 142 women [47%]), 286 (95%) completed the trial. Among the entire cohort, the baseline mean LVEF was 63% (SD, 4.6%) and the follow-up LVEF was 58% (SD, 5.7%). Study drug adherence was noted in 91% of participants. At 12-month follow-up, 46 (15%) had a decline in LVEF of 10% or greater from prior to chemotherapy to a final value of less than 55%. The incidence of the primary end point was 9% (13/150) in the atorvastatin group and 22% (33/150) in the placebo group (P = .002). The odds of a 10% or greater decline in LVEF to a final value of less than 55% after anthracycline treatment was almost 3 times greater for participants randomized to placebo compared with those randomized to atorvastatin (odds ratio, 2.9; 95% CI, 1.4-6.4). Compared with placebo, atorvastatin also reduced the incidence of the secondary end point (13% vs 29%; P = .001). There were 13 adjudicated heart failure events (4%) over 24 months of follow-up. There was no difference in the rates of incident heart failure between study groups (3% with atorvastatin, 6% with placebo; P = .26). The number of serious related adverse events was low and similar between groups., Conclusions and Relevance: Among patients with lymphoma treated with anthracycline-based chemotherapy, atorvastatin reduced the incidence of cardiac dysfunction. This finding may support the use of atorvastatin in patients with lymphoma at high risk of cardiac dysfunction due to anthracycline use., Trial Registration: ClinicalTrials.gov Identifier: NCT02943590.

Background: Few studies have evaluated diagnostic yield of small volume biopsies (SVB) for the diagnosis and management of follicular lymphoma (FL)., Methods: The authors performed a multi-institutional retrospective analysis of SVBs including fine-needle aspiration (FNA) and needle core biopsy (NCB) for initial FL diagnosis and suspected recurrence or transformation of FL. A total of 676 workups beginning with SVB were assessed for the mean number of biopsies per workup, the proportion of workups requiring multiple biopsies, and the proportion with a complete diagnosis including grade, on initial biopsy., Results: Compared to workups performed for question transformation/recurrence, those done for initial FL diagnosis were significantly more likely to require multiple biopsies (p < .01), had a higher mean number of biopsies per workup (1.7 vs. 1.1, absolute standardized difference = 1.1), and a lower complete diagnosis rate at initial biopsy (39% vs. 56%). At initial FL diagnosis, NCB +/- FNA was associated with fewer biopsies per workup compared to FNA +/- CB (1.2 vs. 1.9), fewer workups requiring multiple biopsies (23% vs. 83%), and a higher complete diagnosis rate (71% vs. 18%). In contrast, during assessment for transformation/recurrence, NCB and FNA showed a similar mean number of biopsies per workup (1.2 vs. 1.2) and few workups required multiple biopsies (6% vs. 19%)., Conclusions: SVB at initial FL diagnosis often required additional biopsies to establish a complete diagnosis. In contrast, when assessing for transformed/recurrent FL, additional biopsies were generally not obtained regardless of SVB type, suggesting that in these clinical settings SVB may be sufficient for clinical decision-making., (© 2022 The Authors. Cancer Cytopathology published by Wiley Periodicals LLC on behalf of American Cancer Society.)

ABVD (Adriamycin, bleomycin, vinblastine, dacarbazine) with or without radiation has been the standard treatment for limited-stage Hodgkin lymphoma (HL) but carries risks of bleomycin lung injury and radiation toxicity. Brentuximab vedotin (BV) is approved with AVD for stage III-IV HL, but carries increased risks of peripheral neuropathy (PN) and neutropenic fever, likely due to overlapping toxicity between BV and vinblastine. We therefore evaluated BV in combination with AD for 4 or 6 cycles based on interim positron emission tomography response. Thirty-four patients with nonbulky stage I-II HL were enrolled. Risk was early favorable in 53% and unfavorable in 47%. The overall and complete response rates (CRRs) were 100% and 97%, respectively, with a 5-year progression-free survival (PFS) of 91%. No differences in outcome were observed based on stage (I vs II) or risk status (early favorable vs unfavorable). The most common adverse events were nausea (85%), peripheral sensory neuropathy (59%), and fatigue (56%). There were no cases of grade-4 neutropenia or neutropenic fever, and no patient received granulocyte-colony stimulating factor. Most cases of PN were grade 1, and no patient experienced grade ≥3 PN. BV-AD produced a high CRR and durable PFS with most patients requiring 4 cycles of therapy. Compared with BV-AVD, the toxicity profile appeared improved, with predominantly grade 1 reversible PN and no case of grade 4 neutropenia or neutropenic fever. This regimen warrants further study in HL and may serve as a backbone for the addition of novel agents. This trial is registered on clinicaltrials.gov (NCT02505269)., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

This global phase 3 study compared lisocabtagene maraleucel (liso-cel) with a standard of care (SOC) as second-line therapy for primary refractory or early relapsed (≤12 months) large B-cell lymphoma (LBCL). Adults eligible for autologous stem cell transplantation (ASCT; N = 184) were randomly assigned in a 1:1 ratio to liso-cel (100 × 106 chimeric antigen receptor-positive T cells) or SOC (3 cycles of platinum-based immunochemotherapy followed by high-dose chemotherapy and ASCT in responders). The primary end point was event-free survival (EFS). In this primary analysis with a 17.5-month median follow-up, median EFS was not reached (NR) for liso-cel vs 2.4 months for SOC. Complete response (CR) rate was 74% for liso-cel vs 43% for SOC (P < .0001) and median progression-free survival (PFS) was NR for liso-cel vs 6.2 months for SOC (hazard ratio [HR] = 0.400; P < .0001). Median overall survival (OS) was NR for liso-cel vs 29.9 months for SOC (HR = 0.724; P = .0987). When adjusted for crossover from SOC to liso-cel, 18-month OS rates were 73% for liso-cel and 54% for SOC (HR = 0.415). Grade 3 cytokine release syndrome and neurological events occurred in 1% and 4% of patients in the liso-cel arm, respectively (no grade 4 or 5 events). These data show significant improvements in EFS, CR rate, and PFS for liso-cel compared with SOC and support liso-cel as a preferred second-line treatment compared with SOC in patients with primary refractory or early relapsed LBCL. This trial was registered at www.clinicaltrials.gov as #NCT03575351., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

This study investigated ibrutinib plus obinutuzumab in relapsed/refractory CLL, evaluating tolerability of 3 sequencing regimens as well as overall safety and efficacy. Fifty-two patients were initially randomized 1:1:1 to receive either obinutuzumab 1 month before ibrutinib initiation, ibrutinib 1 month prior to obinutuzumab initiation, or to start both drugs concomitantly. Higher rates of infusion-related reactions were observed with the first sequence, and only the latter 2 cohorts were expanded. Grade 4 hematologic toxicity was uncommon, and notable all-grade non-hematologic toxicities included bruising (58%), hypertension (46%), arthralgia (38%), diarrhea (37%), transaminitis (35%), atrial fibrillation (21%), and serious infection (17%). Best overall response rate was 96% (including 40% CR and 56% PR). Best rates of undetectable minimal residual disease in peripheral blood and bone marrow were 27% and 19%, respectively. With a median follow-up of 41.5 months, four-year progression-free and overall survival rates are 74% and 93%, respectively. Correlative studies demonstrated that serum CCL4 and CXCL13 levels were associated with clinical response, and BH3 profiling revealed increased BCL-2 and BCL-xL dependence in CLL cells from patients on treatment. Overall, ibrutinib plus obinutuzumab was highly active, with a manageable safety profile, supporting further investigation of this type of approach in relapsed/refractory CLL., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

In the TRANSCEND NHL 001 study, 53% of patients with relapsed/refractory large B-cell lymphoma (LBCL) treated with lisocabtagene maraleucel (liso-cel) achieved a complete response (CR). To determine characteristics of patients who did and did not achieve a CR, we examined the tumor biology and microenvironment from lymph node tumor biopsies. LBCL biopsies from liso-cel-treated patients were taken pretreatment and ∼11 days posttreatment for RNA sequencing (RNA-seq) and multiplex immunofluorescence (mIF). We analyzed gene expression data from pretreatment biopsies (N = 78) to identify gene sets enriched in patients who achieved a CR to those with progressive disease. Pretreatment biopsies from month-3 CR patients displayed higher expression levels of T-cell and stroma-associated genes, and lower expression of cell-cycle genes. To interpret whether LBCL samples were "follicular lymphoma (FL)-like," we constructed an independent gene expression signature and found that patients with a higher "FL-like" gene expression score had longer progression-free survival (PFS). Cell of origin was not associated with response or PFS, but double-hit gene expression was associated with shorter PFS. The day 11 posttreatment samples (RNA-seq, N = 73; mIF, N = 53) had higher levels of chimeric antigen receptor (CAR) T-cell densities and CAR gene expression, general immune infiltration, and immune activation in patients with CR. Further, the majority of T cells in the day 11 samples were endogenous. Gene expression signatures in liso-cel-treated patients with LBCL can inform the development of combination therapies and next-generation CAR T-cell therapies., (©2023 The Authors; Published by the American Association for Cancer Research.)