Loncastuximab tesirine in relapsed/refractory diffuse large B-cell lymphoma: Long-term efficacy and safety from the phase II LOTIS-2 study

Therapies that demonstrate durable, long-term responses with manageable safety and tolerability are needed for patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). Loncastuximab tesirine (loncastuximab tesirine-lpyl [Lonca]), an anti-CD19 antibody conjugated to a potent pyrrolobenzodiazepine dimer, demonstrated single-agent antitumor activity in the pivotal phase II LOTIS-2 study in heavily pretreated patients with R/R DLBCL. Here we present updated efficacy and safety analyses from LOTIS-2, performed for all patients and in subsets of patients with a complete response (CR), including patients with CR who were event-free (no progressive disease or death) for ≥1 year and ≥2 years from cycle 1, day 1 of treatment. Lonca was administered every 3 weeks (0.15 mg/kg for 2 cycles; 0.075 mg/kg for subsequent cycles). As of the final data cutoff (September 15, 2022; median follow-up: 7.8 months [range, 0.3-42.6]), 70 of 145 (48.3%) patients achieved an overall response. Thirty-six (24.8%) patients achieved CR, of which 16 (44%) and 11 (31%) were event-free for ≥1 year and ≥2 years, respectively. In the all-treated population, the median overall survival was 9.5 months; the median progression-free survival was 4.9 months. Among patients with CR, median overall survival and progression-free survival were not reached, with 24-month overall and progression-free survival rates of 68.2% (95% CI: 50.0-81.0) and 72.5% (95% CI: 48.2-86.8), respectively. No new safety concerns were detected. With additional follow-up, Lonca continued to demonstrate durable, long-term responses with manageable safety and tolerability in patients with CR (clinicaltrials gov. Identifier: NCT03589469)

Assessment of Regional Variability in COVID-19 Outcomes Among Patients With Cancer in the United States.

Importance: The COVID-19 pandemic has had a distinct spatiotemporal pattern in the United States. Patients with cancer are at higher risk of severe complications from COVID-19, but it is not well known whether COVID-19 outcomes in this patient population were associated with geography. Objective: To quantify spatiotemporal variation in COVID-19 outcomes among patients with cancer. Design, Setting, and Participants: This registry-based retrospective cohort study included patients with a historical diagnosis of invasive malignant neoplasm and laboratory-confirmed SARS-CoV-2 infection between March and November 2020. Data were collected from cancer care delivery centers in the United States. Exposures: Patient residence was categorized into 9 US census divisions. Cancer center characteristics included academic or community classification, rural-urban continuum code (RUCC), and social vulnerability index. Main Outcomes and Measures: The primary outcome was 30-day all-cause mortality. The secondary composite outcome consisted of receipt of mechanical ventilation, intensive care unit admission, and all-cause death. Multilevel mixed-effects models estimated associations of center-level and census division-level exposures with outcomes after adjustment for patient-level risk factors and quantified variation in adjusted outcomes across centers, census divisions, and calendar time. Results: Data for 4749 patients (median [IQR] age, 66 [56-76] years; 2439 [51.4%] female individuals, 1079 [22.7%] non-Hispanic Black individuals, and 690 [14.5%] Hispanic individuals) were reported from 83 centers in the Northeast (1564 patients [32.9%]), Midwest (1638 [34.5%]), South (894 [18.8%]), and West (653 [13.8%]). After adjustment for patient characteristics, including month of COVID-19 diagnosis, estimated 30-day mortality rates ranged from 5.2% to 26.6% across centers. Patients from centers located in metropolitan areas with population less than 250 000 (RUCC 3) had lower odds of 30-day mortality compared with patients from centers in metropolitan areas with population at least 1 million (RUCC 1) (adjusted odds ratio [aOR], 0.31; 95% CI, 0.11-0.84). The type of center was not significantly associated with primary or secondary outcomes. There were no statistically significant differences in outcome rates across the 9 census divisions, but adjusted mortality rates significantly improved over time (eg, September to November vs March to May: aOR, 0.32; 95% CI, 0.17-0.58). Conclusions and Relevance: In this registry-based cohort study, significant differences in COVID-19 outcomes across US census divisions were not observed. However, substantial heterogeneity in COVID-19 outcomes across cancer care delivery centers was found. Attention to implementing standardized guidelines for the care of patients with cancer and COVID-19 could improve outcomes for these vulnerable patients

Neoplastic and non‐neoplastic complications of solid organ transplantation in patients with preexisting monoclonal gammopathy of undetermined significance

Monoclonal gammopathy of undetermined significance (MGUS) occurs in 3–7% of the elderly population, with higher prevalence in renal failure patients, and is associated with a 25‐fold increased lifetime risk for plasma cell myeloma (PCM), also known as multiple myeloma. Using the California State Inpatient, Emergency Department, and Ambulatory Surgery Databases components of the Healthcare Cost and Utilization Project (HCUP), we sought to determine whether patients with MGUS who undergo solid organ allograft (n = 22 062) are at increased adjusted relative risk (aRR) for hematologic malignancy and other complications. Among solid organ transplant patients, patients with preexisting MGUS had higher aRR of PCM (aRR 19.46; 95% CI 7.05, 53.73; p < 0.001), venous thromboembolic events (aRR 1.66; 95% CI 1.15, 2.41; p = 0.007), and infection (aRR 1.24; 95% CI 1.06, 1.45; p = 0.007). However, when comparing MGUS patients with and without solid organ transplant, there was decreased aRR for PCM with transplant (aRR 0.34; 95% CI 0.13, 0.88; p = 0.027), and increased venous thromboembolic events (aRR 2.33; 95% CI 1.58, 3.44; p < 0.001) and infectious risks (aRR 1.44; 95% CI 1.23, 1.70; p < 0.001). While MGUS increased the risk of PCM overall following solid organ transplantation, there was lower risk of PCM development compared to MGUS patients who did not receive a transplant. MGUS should not preclude solid organ transplant.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/113779/1/ctr12595_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/113779/2/ctr12595.pd

Clinical, Imaging Findings, Responses, and Outcomes of Patients With Classical Hodgkin Lymphoma and Non-Hodgkin Lymphoma Undergoing Immune Checkpoint Inhibitor Therapy: A Single-Institution Experience

WOS: 000559758400024PubMed: 32558769Objective the aim of the study was to study clinical, imaging findings, response patterns, and immune-related adverse events in classical Hodgkin lymphoma (cHL) and non-Hodgkin lymphoma (NHL) patients treated with immune checkpoint inhibitors (ICIs). Methods A retrospective search was performed to identify patients with relapsed/refractory cHL and NHL treated with ICIs from 2015 to 2019. Clinical and laboratory data were collected. Imaging studies were reviewed for treatment response and immune-related adverse events. Results Ten patients with relapsed/refractory cHL (median age, 41 years) and 14 patients with relapsed/refractory NHL (median age, 61 years) were identified. Overall response rate was 70% for cHL patients. None of the NHL patients demonstrated complete or partial response. One case of hyperprogression and one case with atypical response were radiologically detected in cHL patients. Hypothyroidism requiring treatment occurred in 2 (20%) of 10 cHL patients, one of which had imaging correlate. of 14 NHL patients, 1 (7%) had radiologic evidence of pneumonitis and 1 (7%) had colitis. Conclusions This single-institution observational study demonstrated that overall response rate was higher in patients with cHL undergoing ICI. Immune checkpoint inhibitor therapy has unique response patterns and toxicities in both cHL and NHL patients that radiologists should keep in mind