Cytomegaloviral Infections in Recipients of Chimeric Antigen Receptor T-Cell Therapy: An Observational Study With Focus on Oncologic Outcomes.

Background: Patients with B-cell lymphoma and acute lymphoblastic leukemia (ALL) who receive chimeric antigen receptor T-cell (CAR-T) therapy may experience clinically significant cytomegalovirus infection (CS-CMVi). However, risk factors for CS-CMVi are not well defined. The aims of our study were to identify risk factors for CS-CMVi and the association between CS-CMVi and nonrelapse mortality (NRM) in lymphoma and ALL patients after CAR-T therapy. Methods: We performed a retrospective single-center cohort analysis of CAR-T recipients between January 2018 and February 2021 for treatment of lymphoma and ALL. We collected data on demographics, oncologic history, CAR-T therapy-related complications, and infectious complications within 1 year of therapy. Results: Of 230 patients identified, 22 (10%) had CS-CMVi. At 1 year following CAR-T therapy, 75 patients (33%) developed relapsed disease and 95 (41%) died; NRM at 1 year was 37%. On Cox regression analysis, Asian or Middle Eastern race (adjusted hazard ratio [aHR], 13.71 [95% confidence interval {CI}, 5.41-34.74]), treatment of cytokine release syndrome/immune effector cell-associated neurotoxicity syndrome with steroids (aHR, 6.25 [95% CI, 1.82-21.47]), lactate dehydrogenase at time of CAR-T therapy (aHR, 1.09 [95% CI, 1.02-1.16]), and CMV surveillance (aHR, 6.91 [95% CI, 2.77-17.25]) were independently associated with CS-CMVi. CS-CMVi was independently associated with NRM at 1 year after CAR-T therapy (odds ratio, 2.49 [95% CI, 1.29-4.82]). Conclusions: Further studies of immunologic correlatives and clinical trials to determine the efficacy of prophylactic strategies are needed to understand the role of CS-CMVi and post-CAR-T mortality.

The CNS relapse in T-cell lymphoma index predicts CNS relapse in patients with T- and NK-cell lymphomas.

ABSTRACT: Little is known about risk factors for central nervous system (CNS) relapse in mature T-cell and natural killer cell neoplasms (MTNKNs). We aimed to describe the clinical epidemiology of CNS relapse in patients with MTNKN and developed the CNS relapse In T-cell lymphoma Index (CITI) to predict patients at the highest risk of CNS relapse. We reviewed data from 135 patients with MTNKN and CNS relapse from 19 North American institutions. After exclusion of leukemic and most cutaneous forms of MTNKNs, patients were pooled with non-CNS relapse control patients from a single institution to create a CNS relapse-enriched training set. Using a complete case analysis (n = 182), including 91 with CNS relapse, we applied a least absolute shrinkage and selection operator Cox regression model to select weighted clinicopathologic variables for the CITI score, which we validated in an external cohort from the Swedish Lymphoma Registry (n = 566). CNS relapse was most frequently observed in patients with peripheral T-cell lymphoma, not otherwise specified (25%). Median time to CNS relapse and median overall survival after CNS relapse were 8.0 and 4.7 months, respectively. We calculated unique CITI risk scores for individual training set patients and stratified them into risk terciles. Validation set patients with low-risk (n = 158) and high-risk (n = 188) CITI scores had a 10-year cumulative risk of CNS relapse of 2.2% and 13.4%, respectively (hazard ratio, 5.24; 95% confidence interval, 1.50-18.26; P = .018). We developed an open-access web-based CITI calculator (https://redcap.link/citicalc) to provide an easy tool for clinical practice. The CITI score is a validated model to predict patients with MTNKN at the highest risk of developing CNS relapse.

Evolving Landscape of Antibody Drug Conjugates in Lymphoma.

ABSTRACT: Despite the curative potential of autologous transplantation and chimeric antigen receptor T cells in lymphoma, many patients are ineligible, or their disease progresses after these treatments. In this context, antibody drug conjugates (ADCs) have demonstrated very promising efficacy in lymphomas. Antibody drug conjugates are monoclonal antibodies covalently linked to a cytotoxic drug. Because of its highly specific targeting abilities and powerful killing effects, it has become a promising technology for developing anticancer drugs in recent years. The US Food and Drug Administration has approved 14 ADCs since Mylotarg (gemtuzumab ozogamicin) entered the market in 2000. With advances in the design of ADCs, their efficacy and safety have moved in tandem, and many novel ADCs have gained growing interest. Three ADCs, brentuximab vedotin, polatuzumab vedotin, and loncastuximab tesirine, have been approved for treating lymphoma. The rapidly evolving ADC arsenal for treating relapsed or refractory lymphoma offers many choices. The article reviews the history and general mechanism of action of ADCs. This is followed by a discussion of the molecular aspects of their key components and their mechanisms of influence on their design and function. Finally, we review up-to-date clinical data of the approved and emerging targets of ADCs in lymphoma.