PURPOSE Patients with non-Hodgkin lymphoma including chronic lymphocytic leukemia (NHL/CLL) are at higher risk of severe SARS-CoV-2 infection. We investigated vaccine-induced antibody responses in patients with NHL/CLL against the original SARS-CoV-2 strain and variants of concern including B.1.167.2 (Delta) and B.1.1.529 (Omicron). MATERIALS AND METHODS Blood from 121 patients with NHL/CLL receiving two doses of vaccine were collected longitudinally. Antibody binding against the full-length spike protein, the receptor-binding, and N-terminal domains of the original strain and of variants was measured using a multiplex assay. Live-virus neutralization against Delta, Omicron, and the early WA1/2020 strains was measured using a focus reduction neutralization test. B cells were measured by flow cytometry. Correlation between vaccine response and clinical factors was determined. RESULTS Mean anti-SARS-CoV-2 spike immunoglobulin G–binding titers were 85-fold lower in patients with NHL/CLL compared with healthy controls, with seroconversion occurring in only 67% of patients. Neutralization titers were also lower and correlated with binding titers ( P < .0001). Treatment with anti-CD20-directed therapies within 1 year resulted in 136-fold lower binding titers. Peripheral blood B-cell count also correlated with vaccine response. At 3 months from last anti-CD20-directed therapy, B-cell count ≥ 4.31/μL blood around the time of vaccination predicted response (OR 7.46, P = .04). Antibody responses also correlated with age. Importantly, neutralization titers against Delta and Omicron were reduced six- and 42-fold, respectively, with 67% of patients seropositive for WA1/2020 exhibiting seronegativity for Omicron. CONCLUSION Antibody binding and live-virus neutralization against SARS-CoV-2 and its variants of concern including Delta and Omicron were substantially lower in patients with NHL/CLL compared with healthy vaccinees. Anti-CD20-directed therapy < 1 year before vaccination and number of circulating B cells strongly predict vaccine response.

Prophylaxis is commonly used to prevent central nervous system (CNS) relapse in diffuse large B cell lymphoma, with no clear standard of care. We retrospectively evaluated 1162 adult patients across 21 US academic centers with DLBCL or similar histologies who received single-route CNS prophylaxis as part of frontline therapy between 2013-2019. Prophylaxis was administered intrathecally (IT) in 894 (77%) and using systemic high-dose methotrexate (HD-MTX) in 236 (20%); 32 patients (3%) switched route due to toxicity and were assessed separately. By CNS-International Prognostic Index (IPI), 18% were considered low-risk, 51% moderate, and 30% high. Double-hit lymphoma (DHL) was confirmed in 243 of 866 evaluable patients (21%). Sixty-four patients (5.7 %) had CNS relapse, after median 7.1 months from diagnosis, including 15 of 64 (23%) within the first 6 months. There was no significant difference in CNS relapse between IT and HD-MTX recipients (5.4 vs 6.8%, p=0.4), including after propensity score matching to account for differences between respective recipient groups. Weighting by CNS-IPI, expected versus observed CNS relapse rates were nearly identical (5.8 vs 5.7%). Testicular involvement was associated with high risk of CNS relapse (11.3%) despite most having lower CNS-IPI scores. DHL did not significantly predict for CNS relapse after single-route prophylaxis, including with adjustment for treatment regimen and other factors. This large study of CNS prophylaxis recipients with DLBCL found no significant difference in CNS relapse rates between routes of administration. Relapse rates among high-risk subgroups remain elevated and reconsideration of prophylaxis strategies in DLBCL is of critical need.

A qualitative study of lymphoma survivors living in rural Georgia was conducted using 12 individual semistructured telephone interviews. The travel distance was the greatest barrier to care, with other issues including communication and navigating between local clinics and larger cancer centers. The participants saw technology as an important solution and detailed their research priorities. Background: We gathered rural patient perspectives on lymphoma care and unmet needs throughout the treatment course to better understand their attitudes toward treatment and their barriers to participating in clinical research studies. Patients and Methods: We conducted 12 individual semi-structured telephone interviews in the spring of 2018 with lymphoma survivors from rural counties in Georgia. Patients were identified by a residential address in counties classified as rural according to the Rural-Urban Commuting Areas codes. Participants were recruited from regional patient education conferences and from current research participants at a university research hospital in Georgia. The interviews were recorded and transcribed verbatim. Thematic analysis and MAXQDA, version 18.0.8, were used to facilitate a constant comparative coding process during theme development. Results: The greatest barrier to care was the travel distance. The participants described difficulty navigating between local clinics and larger cancer centers. The lack of communication between the local and specialized clinics complicated the process, and participants had difficulty contacting or seeking advice from the team at the larger cancer centers. Seeking treatment from specialized clinics farther away introduced additional barriers. Most participants agreed that the use of technology was important for improved communication. Participants described lymphoma etiology, subtype-specific studies, alternative therapies, and quality of life as key research priorities. Conclusion: These findings suggest that targeted research and interventions are necessary to address the specific needs of rural patients with and survivors of lymphoma. To address the disparity in health outcomes within rural populations, healthcare professionals and investigators can use these data to engage rural patients in treatment decision-making and research planning.

Polatuzumab vedotin (PV) is an antibody-drug conjugate targeting CD79b that is approved for patients with relapsed/refractory (r/r) large B-cell lymphoma (LBCL). Patients who relapse after CAR T-cell therapy were not included in the registration study, and reports of PV use after CAR T-cells are limited. This is a multi-center retrospective analysis of patients with LBCL who relapsed or progressed after CAR T-cell therapy and subsequently received PV with or without rituximab and bendamustine, between 07/2019 and 05/2021. Response to treatment and progression were assessed based on 2014 Lugano criteria. Fifty-seven patients were included in the study: 18 (32%) patients were primary refractory to CAR T-cell therapy, and 34 (60%) patients received PV-based therapy immediately after CAR T cell therapy. PV was combined with rituximab in 54 (95%) patients and administered with bendamustine in 35 (61%). A response was achieved in 25 (44%) patients, including complete remission in 8 (14%) patients. No significant association between baseline characteristics and response was observed. After a median follow up of 47 weeks (95% confidence interval [CI], 40-54 weeks), 46 (81%) patients had progressed or died, and the median PFS was 10 weeks (95% CI, 5-15 weeks). On a multivariate analysis, bone marrow involvement (hazard ratio [HR] 5.2; 95% CI 1.8-15, p=0.003) and elevated LDH (HR 5.0; 95% CI 1.4-16, p=0.01) were associated with shorter PFS. Studies aimed at better characterizing intrinsic mechanism of resistance and to identify optimal consolidation strategies for these patients are warranted.