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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.)

Introduction: The American Joint Committee on Cancer (AJCC) eighth staging classification system for non-small-cell lung cancer was based on data from a multinational study consisting of 94,708 patients. African Americans were not included in this large database., Materials and Methods: The authors aimed to compare the performance of the AJCC eighth staging system with that of the seventh in predicting overall survival among African Americans utilizing the National Cancer Database. Cases with T- and M- categories were classified into 2 groups based on the AJCC seventh and eighth edition staging systems. Kaplan-Meier curves for overall survival were then constructed for each subgroup. Concordance index was computed using Uno's methodology to assess the overall performance between the 2 staging systems in predicting the mortality. Time-dependent area under the curve was calculated at each follow-up event for the seventh and eighth edition clinical and pathologic staging using an inverse probability of censoring weighted methodology. A 2-sided P-value < .05 was considered to show statistical significance., Results: The database identified a total of 70,606 African American patients in the study period of 2004 through 2014. Area under the curve values were consistently higher for the eighth edition scheme compared with the seventh edition (concordance 0.630 vs. 0.624, respectively; P < .0001 for clinical staging scheme and 0.596 vs. 0.591, respectively; P = .01 for pathologic staging scheme)., Conclusion: The AJCC eighth edition staging system showed better prognostic value in predicting overall survival when compared with the AJCC seventh edition staging scheme among African American patients with non-small-cell lung cancer., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Targeting of somatic MET mutations using crizotinib has led to strong clinical responses, most frequently in patients with lung cancer, raising the possibility of adopting similar treatment strategies in patients with MET alterations in other cancer types., Patient and Methods: We describe a patient with advanced triple-negative breast cancer with a 30-fold amplification of MET. Next-generation sequencing of pre- and postprogression biopsies was performed to identify the resistance mechanism emerging after an initial exceptional response to crizotinib. The response of the resistance mutant to type I and II MET inhibitors was assessed in cultured cells., Results: After progressing on crizotinib, a MET-D1228N mutation was detected, which is located in the crizotinib-binding region of the MET kinase domain. Experimental studies demonstrated that this mutation confers complete resistance to crizotinib yet retains cabozantinib sensitivity. Treatment of the patient with cabozantinib led to a subjective improvement in clinical symptoms, but the patient progressed after 7 weeks., Conclusion: Although MET mutations are rare in breast cancer, these patients may experience substantial clinical benefit from crizotinib treatment. Nevertheless, drug resistance owing to on-target MET mutations will likely be frequently encountered and comprehensive mechanistic studies to assess sensitivity of these mutants to a series of potential second-line therapies may help guide subsequent treatment for these patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: For patients with T1 or T2 N0 M0 small-cell lung cancer (SCLC), lobectomy followed by chemotherapy is the standard of care. However, because of its tendency for early dissemination, patients are often treated with concurrent chemo-radiation without surgery. This study was conducted to evaluate the utilization of surgery and its impact on survival in patients with early stage SCLC., Materials and Methods: The National Cancer Database was queried to identify patients with T1 or T2 N0 M0 SCLC diagnosed from 2004 to 2013. Multivariate logistic regression modeling was utilized to identify factors associated with receipt of surgery. Patients were stratified into 3 groups: chemo-radiation, surgery followed by chemotherapy, and surgery followed by chemotherapy and prophylactic cranial irradiation (PCI). Kaplan-Meier estimators and Cox proportional-hazards regression were used to compare overall survival. Patients were matched on the propensity score., Results: A total of 3879 SCLC cases were identified. Of those cases, 80.7% received chemo-radiation. Surgery followed by chemotherapy with or without PCI was associated with better median overall survival (93.0 months [lower 95% confidence interval (CI), 72.5] and 61.7 months [95% CI, 51.8-76.5], respectively) compared with chemo-radiation (31.2 months [95% CI, 26.3-37.0]). PCI offered survival benefit in addition to surgery and chemotherapy (hazard ratio, 0.75)., Conclusions: Our study showed a significant survival benefit with surgery (lobectomy or more), adjuvant chemotherapy, and PCI in patients with T1-T2 N0 M0 SCLC., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Although the treatment of metastatic melanoma has been significantly improved by both anti-BRAF/MEK and checkpoint immunotherapies, resistance to these treatment modalities remains a substantial clinical problem. Multiple clinical studies are addressing the optimal sequencing of these agents in larger patient cohorts, but successful long-term individualized treatment will likely require the elucidation of resistance mechanisms from post-progression samples. Here, we describe a patient with BRAF-V600E-positive metastatic melanoma who was sequentially treated with BRAF/MEK inhibitors (dabrafenib/trametinib) and checkpoint inhibitor immunotherapy (nivolumab, followed by pembrolizumab). After the emergence of resistance, whole exome sequencing was performed, implicating MAP2K2 and B2M mutations in loss of response to anti-BRAF/MEK and anti-PD1 therapies, respectively., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Recent observational studies are concerning because they document rising mastectomy rates coinciding with more than a dozen reports that lumpectomy has better overall survival (OS) than mastectomy. Our aim was to determine if there were differences in OS of matched breast cancer patients undergoing lumpectomy versus mastectomy in the National Cancer Database (NCDB)., Patients and Methods: A retrospective cohort of patients with stage I-III breast cancer in the NCDB (2004-2013) was identified. Propensity score matching (PSM), Kaplan-Meier, and multivariate Cox proportional hazards models were used to examine OS by type of surgery., Results: Of 845,136 patients, 464,052 (54.9%) underwent lumpectomy and 381,084 (45.1%) underwent mastectomy. After PSM, the hazard ratio (HR) and confidence interval (CI) for OS in all patients comparing lumpectomy with mastectomy was 1.02 (CI, 1.00-1.04; P = .002). In patients with stage I, II, and III, they were HR 1.27 (CI, 1.23-1.36; P < .001), HR 0.98 (CI, 0.95-1.01; P = .21), and HR 0.83 (CI, 0.80-0.86; P < .001), respectively. In subgroup analyses of all patients by estrogen receptor (ER) status, they were HR 1.05 (CI, 1.03-1.07; P < .001) and HR 1.00 (CI, 0.96-1.03; P = .65) in ER+ and ER- patients., Conclusion: In our primary model of all stage I-III matched patients, using the most recent NCDB data and the largest observational sample size to date, the OS after mastectomy was not inferior to lumpectomy. This finding can be reassuring to patients and providers. In subgroup analyses, the association between type of surgery and OS differed by cancer stage and hormone receptor status., (Copyright © 2019 Elsevier Inc. All rights reserved.)

We investigated a recent (January 1999 to December 2009) cohort of 95 elderly Hodgkin lymphoma subjects. At diagnosis, median age was 67 years (range, 60-89 years), whereas 61% had significant comorbidity, 26% were unfit, 17% had a geriatric syndrome, and 13% had loss of activities of daily living. Overall response rate to therapy was 85%, whereas incidence of bleomycin lung toxicity was 32% (with associated mortality rate, 25%). With 66-month median follow-up, 2-year and 5-year overall survival were 73% and 58%, respectively (advanced-stage, 63% and 46%, respectively). Most International Prognostic Score factors were not prognostic on univariate analyses, whereas Cox multivariate regression identified 2 risk factors associated with inferior overall survival: (1) age more than 70 years (2.24; 95% CI, 1.16-4.33, P = .02) and (2) loss of activities of daily living (2.71; 95% CI, 1.07-6.84, P = .04). Furthermore, a novel survival model based on number of these risk factors (0, 1, or 2) showed differential 2-year OS of 83%, 70%, and 13%, respectively (P < .0001) and 5-year OS of 73%, 51%, and 0%, respectively (P < .0001).