Sequencing of cellular therapy and bispecific antibodies for the management of diffuse large B-cell lymphoma.

Historically, management of relapsed or refractory (R/R) Diffuse large B-cell (DLBCL) following first-line chemoimmunotherapy has been second-line chemotherapy, followed by high-dose chemotherapy and consolidative autologous hematopoietic stem cell transplantation (auto-HSCT), resulting in durable remissions in approximately 40% of patients. In 2017, chimeric antigen receptor (CAR) T-cell therapy changed the landscape of treatment for patients with R/R DLBCL, with complete response rates ranging from 40-58% and long-term disease-free survival of >40% in the highest risk subgroups, including patients who relapsed after auto-HSCT. Since that time further studies have demonstrated improved overall response rates (ORRs) and survival outcomes in patients with primary refractory or early-relapse (relapse 50% of patients will relapse in the post-CAR T-cell setting. In the past two years, two CD20 x CD3 bispecific antibodies (BsAbs) were FDA approved for the treatment of R/R DLBCL after two or more lines of systemic therapy. These BsAbs have demonstrated ORRs exceeding 50% and durable remissions at > 2yrs of follow-up. Additionally, a notable treatment advantage of BsAbs is their ability to be administered in the community setting, making treatment more accessible for patients. The development and advancement of these novel therapies raise questions regarding the ongoing role of HSCT in the management of relapsed and refractory DLBCL and how to best sequence cellular and Bi-specific therapies to optimize patient outcomes.

Checkpoint inhibitor myocarditis with preceding immunosuppression and tolerance of sequential anthracycline therapy.

A man in his 50s with no known cardiac history and diffuse large B-cell lymphoma on nivolumab presented with acute dyspnoea and swelling. Physical examination revealed volume overload. Work-up noted new elevation of B-type natriuretic peptide and troponin, with new lateral T-wave inversions on ECG. He was admitted to cardiac intensive care for decompensated heart failure. Echocardiography showed ejection fraction 51% with diffuse hypokinesis and reduction of global longitudinal strain. Cardiac MRI demonstrated diffuse myocardial fibrosis with oedema suggesting acute injury. Endomyocardial biopsy revealed lymphocytic and macrophagic infiltrate with cardiomyocyte damage, compatible with immune checkpoint inhibitor (ICI) myocarditis. Immunotherapy was discontinued and he was treated with diuresis, steroids and initiation of goal-directed medical therapy for heart failure. He required additional treatment with anthracyclines. He was monitored with cardio-oncology follow-up after every cycle of anthracycline and tolerated a cumulative 312 mg/m2 therapy. The safety of anthracycline administration after ICI-myocarditis has not been described.

Impact of race and social determinants of health on outcomes in patients with aggressive B-cell NHL treated with CAR-T therapy.

ABSTRACT: Chimeric antigen receptor (CAR) T-cell (CAR-T) immunotherapy is an effective therapy for relapsed/refractory B-cell non-Hodgkin lymphoma (r/r B-NHL). However, data are limited on the impact of the convergence of race and social determinants of health on outcomes for patients treated with CAR-T therapy. We examined the impact of interactions between race and insurance type on health care use and outcomes in patients treated with CAR-T therapy for aggressive B-NHL. Adult patients with r/r B-NHL treated with CD19 CAR-Ts were identified between 2015 and 2021 across 13 US academic centers. Insurance type, demographic, and clinical data were collected and analyzed. In total, 466 adult patients were included in our analysis. Median follow-up after CAR-T therapy was 12.7 months. Median progression-free survival (mPFS) was longer for Caucasians (11.5 months) than for African Americans (3.5 months; hazard ratio [HR], 1.56 [1.03-2.4]; P = .04) or Asians (2.7 months; HR, 1.7 [1.02-2.67]; P = .04). Differences in median overall survival (mOS) were not significant. For Medicare (n = 206) vs Medicaid (n = 33) vs private insurance (n = 219) vs self-pay (n = 7): mPFS was 15.9 vs 4.2 vs 6.0 vs 0.9 months (P < .001), respectively; and mOS was 31.2 vs 12.8 vs 21.5 vs 3.2 months (P < .001), respectively. Our multicenter retrospective analysis showed that race and insurance status can affect outcomes for patients treated with CAR-T therapy.