Incidence of second primary malignancies in patients with multiple myeloma receiving anti-CD38 monoclonal antibodies: A systematic review and meta-analysis.

Anti-CD38 monoclonal antibodies (mAbs) are commonly used for treating newly diagnosed and relapsed/refractory (r/r) multiple myeloma (MM). However, concerns have been raised about the occurrence of second primary malignancies (SPMs) in patients receiving anti-CD38 mAbs. Assessing the safety data for rare adverse events like SPMs is challenging because individual clinical trials are typically focused on the primary endpoint. Therefore, we conducted a meta-analysis of randomized controlled trials (RCTs) published between January 2005 and April 2022, including patients with newly diagnosed or r/r MM. Our aim was to compare SPM rate with the use of anti-CD38 mAb-based regimens with other anti-myeloma regimens. After a median follow-up of 35.3 months (range: 8.2-56.2), we found that exposure to anti-CD38 mAbs was associated with an increased risk of developing SPMs compared to the control group (6.8% vs. 5.2%; Peto odds ratio [OR]: 1.53 [95% confidence interval (CI): 1.20-1.95]; I2= 0%, p-value for heterogeneity= 0.44). This increased risk was primarily driven by non-melanoma cutaneous cancers (92 vs. 47; Peto OR: 1.77 [95% CI: 1.25-2.51]; I2 = 0%, p-value for heterogeneity = 0.54). However, there was no significant difference in the incidence of solid tumors (including malignant melanoma) (OR: 1.28 [95% CI: 0.85-1.95]) or hematologic SPMs (OR: 1.86; [95% CI: 0.81-4.27]). In conclusion, the use of anti-CD38 mAb-based combination regimens is associated with a higher risk of non-invasive cutaneous SPMs, but not solid tumors or hematologic SPMs. The increased occurrence of non-invasive cutaneous SPMs may be due to enhanced monitoring resulting from longer treatment duration with anti-CD38 mAbs.

Bladder cancer: shedding light on the most promising investigational drugs in clinical trials.

Introduction: Urothelial cancers (UC) include tumors of the bladder, upper tract, and proximal urethra. Bladder cancer (BC) arises from urothelial cells lining the bladder and accounts for 90-95% of UC. BC is responsible for approximately 500,000 new cases and has a dismal prognosis with 200,000 deaths annually globally. However, immune checkpoint inhibitors (ICIs) and antibody-drug conjugates are rapidly changing the treatment landscape. Novel therapies are building on this success and are being intensively investigated in clinical trials.Areas Covered: This paper examines the clinical trial data by searching Medline through January 2021 and clinicaltrials.gov and conference proceedings from the latest ASCO and ESMO meetings. We summarize the emerging data from clinical trials and offer insights into mechanisms of novel agents, nuances in clinical trial designs, and future directions.Expert Opinion: Approval of multiple ICIs, Enfortumab Vedotin (EV), Erdatfitinib and switch maintenance strategy with Avelumab, represent major advances in metastatic disease. ICI agents and EV are well poised to move forward for treating the early stages of bladder cancer. Finally, molecular characterization of the tumor offers hope for personalized treatment approaches.

Venous thromboembolism risk with contemporary lenalidomide-based regimens despite thromboprophylaxis in multiple myeloma: A systematic review and meta-analysis.

BACKGROUND: Thromboprophylaxis is routinely used with lenalidomide-based regimens in multiple myeloma because of a substantial risk of venous thromboembolism (VTE). However, little is known about the incidence of VTE with contemporary lenalidomide-based regimens. The objective of the current study was to estimate the incidence of VTE despite thromboprophylaxis with currently used lenalidomide-based regimens in patients with myeloma. METHODS: The Ovid MEDLINE, Embase, and Cochrane databases were queried from study inception to January 2019 for keywords to cover the following concepts: "lenalidomide," "venous thromboembolism," and "multiple myeloma." Phase 1, 2, and 3 clinical trials evaluating lenalidomide-based regimens with thromboprophylaxis were included. The pooled incidence rate of VTE was estimated using a random-effects model. RESULTS: The search generated 1372 citations, with 51 clinical trials and 9069 patients included for analysis. The most common thromboprophylaxis agents were aspirin, low-molecular-weight heparin or warfarin, administered either per risk-stratification or at investigators' discretion. The pooled incidence of VTE in trials of patients who had newly diagnosed and relapsed/refractory myeloma was 6.2% (95% CI, 5.4%-7.1%) over median treatment durations ranging from 2 to 34 cycles, which translated into 1.2 VTE events per 100 patient-cycles (95% CI, 0.9-1.7 VTE events per 100 patient-cycles). Among contemporary regimens, the risk of VTE was low with combined lenalidomide and low-dose dexamethasone (0.2 [95% CI, 0.1-0.6] events/100 patient-cycles) and lenalidomide maintenance (0.0 [95% CI, 0.0-0.7] events per 100 patient-cycles). VTE risk was higher with combined lenalidomide and low-dose dexamethasone plus proteasome inhibitors (1.3 [95% CI, 0.7-2.3] events per 100 patient-cycles). CONCLUSIONS: Despite adequate thromboprophylaxis, lenalidomide-based regimens have a substantial risk of VTE in controlled clinical trial settings. Further studies are needed on new thromboprophylaxis strategies with regimens that have a high VTE risk.

Male breast cancer in the United States: Treatment patterns and prognostic factors in the 21st century.

BACKGROUND: Male breast cancer (MBC) is a rare disease for which there is limited understanding of treatment patterns and prognostic factors. METHODS: Men with TNM stage I to stage III breast cancer diagnosed between 2004 and 2014 in the National Cancer Data Base were included. Trends in treatment modalities were described using the average annual percentage change (AAPC) and estimated using Joinpoint software for the analysis of trends. Kaplan-Meier curves and the multivariate Cox proportional hazards regression model were used to compare survival between subgroups and to identify prognostic factors. RESULTS: A total of 10,873 MBC cases were included, with a median age at diagnosis of 64 years. Breast-conserving surgery was performed in 24% of patients, and 70% of patients undergoing breast conservation received radiotherapy. Approximately 44% of patients received chemotherapy, and 62% of patients with estrogen receptor-positive disease received endocrine therapy. Oncotype DX was ordered in 35% of patients with lymph node-negative, estrogen receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative tumors. During the study period, there was a significant increase in the rates of total mastectomy, contralateral prophylactic mastectomy, radiotherapy after breast conservation, ordering of Oncotype DX, and the use of endocrine therapy (P < .05). On multivariate analysis, factors found to be associated with worse overall survival were older age, black race, higher Charlson Comorbidity Index, high tumor grade and stage of disease, and undergoing total mastectomy. Residing in a higher income area; having progesterone receptor-positive tumors; and receipt of chemotherapy, radiotherapy, and endocrine therapy were associated with better overall survival. CONCLUSIONS: Despite the lack of prospective randomized trials in patients with MBC, the results of the current study demonstrated that the treatment of this disease has evolved over the years. These findings further the understanding of the modern treatment and prognosis of MBC, and identify several areas for further research.

Neoadjuvant vs. adjuvant chemotherapy for cholangiocarcinoma: A propensity score matched analysis.

BACKGROUND: Chemotherapy is frequently used in cholangiocarcinoma as an adjunct to surgical resection, but the appropriate sequence of chemotherapy with surgery is unclear. PATIENTS AND METHODS: Using the National Cancer Database, we identified patients who underwent surgery and chemotherapy for stage I-III cholangiocarcinoma between 2006 and 2014. The propensity score reflecting the probability of receiving neoadjuvant chemotherapy was estimated by multivariate logistic regression method. Patients in the neoadjuvant and adjuvant chemotherapy study arms were then propensity-matched in 1:3 ratios using the nearest neighbor method. Overall Survival (OS) in the matched data set was estimated using the Kaplan-Meier method. Hazard ratios (HRs) were calculated using Cox proportional hazard regression model. RESULTS: Of the 1450 patients who met our inclusion criteria, 299 (20.6%) received neoadjuvant chemotherapy while 1151 (79.3%) received adjuvant chemotherapy. The median age at diagnosis was 63 years. 278 patients in the neoadjuvant group were matched to 700 patients in the adjuvant group. In the matched cohort, patients who received neoadjuvant chemotherapy had a superior OS compared to those who received adjuvant chemotherapy (Median OS: 40.3 vs. 32.8 months; HR: 0.78; 95% CI: 0.64-0.94, p = 0.01). The 1- and 5-year OS rates for the neoadjuvant chemotherapy group were 85.8% and 42.5% respectively compared to 84.6% and 31.7% for the adjuvant chemotherapy group. CONCLUSION: In this large national database study, neoadjuvant chemotherapy was associated with a longer OS in a select group of patients with cholangiocarcinoma compared to those who underwent upfront surgical resection followed by adjuvant chemotherapy.

Bortezomib, lenalidomide, and dexamethasone (VRd) followed by autologous stem cell transplant for multiple myeloma.

We retrospectively reviewed all patients (n = 243) receiving bortezomib, lenalidomide, and dexamethasone (VRd) induction followed by autologous stem cell transplantation (ASCT) for multiple myeloma at the Mayo Clinic between January 2010 and April of 2017. Median age was 61 (interquartile range, 55-67) with 62% of patients being male. High-risk cytogenetic abnormalities (HRA) were present in 34% of patients. A total of 166 (68%) patients received some form of maintenance/other therapy post transplant (no maintenance (NM, n = 77), lenalidomide maintenance (LM, n = 108), bortezomib maintenance (BM, n = 39), and other therapy (OT, n = 19)). Overall response rate at day 100 post ASCT was 99% (CR 42%) with CR rate increasing to 62% at time of best response post transplant. Two year and 5 year overall survival rates were 90% and 67%, respectively, with an estimated median overall survival (OS) and progression-free survival (PFS) of 96 and 28 months, respectively. HRA was associated with a worse OS but not PFS (median OS: not reached for standard risk vs 60 months for HRA, P = 0.0006; median PFS: 27 months for standard risk vs 22 months for HRA, P = 0.70). The combination of VRd followed by ASCT is a highly effective regimen producing deep and durable responses in many patients.

Disease Milestones through Bibliometric Analysis of the Top 100 Cited Articles in Multiple Myeloma.

Multiple myeloma (MM) accounts for 1.6% of all cancers and 5%-10% of all hematologic malignancies in the United States (US). Despite marked progress in disease management, it remains incurable with high rates of relapse. We conducted a bibliographic analysis on the Web of Science (WOS) from July 25, 2017 and July 29, 2017. Among the top 100 most-cited articles (1901-2012), the most cited article received 2404 citations and least cited article received 336 citations. Forty-four of 100 articles were published in journals with impact factors greater than 20. We observed that over the years, the focus of research has shifted from diagnosis, staging, and pathogenesis to better treatment outcomes. A subgroup analysis of the top 100 cited articles published in the last five years (2012-2017) demonstrated that several landmark studies, which will likely change the landscape of treating multiple myeloma, were not included in the top 100 list. Interestingly, most of these articles were focused on novel therapeutic agents. This bibliographic analysis provides a list of the 100 top-cited articles in multiple myeloma along with the captivating comprehension of the history and development in various aspects of disease processes. The landscape of this disease is rapidly evolving, and bibliometric studies such as the one presented provide a valuable tool that can highlight the important transitions in the field.

Role of one, two and three doses of high-dose chemotherapy with autologous transplantation in the treatment of high-risk or relapsed testicular cancer: a systematic review.

Approximately 20-30% of patients with metastatic germ cell cancers (GCCs) can develop relapsed or refractory (RR) disease, about 40-50% of patients who relapse after salvage chemotherapy may reach long-term remission. The goal of this review was to identify patients who appear to benefit from high-dose chemotherapy (HDCT) and autologous stem cell transplant (ASCT). To access this, we performed a systematic medical literature review to evaluate the effectiveness of HDCT in the frontline setting, as well as in patients with RR testicular cancer. We searched databases for interventional clinical studies and identified 5883 studies. We selected 49 studies for inclusion, which included a total of 5985 patients. Seventeen studies reported results of newly diagnosed poor-risk GCC patients and 32 studies reported results of RR patients. For newly diagnosed patients with poor prognostic predictors, a risk adjusted strategy using unfavorable tumor marker decline with initial standard chemotherapy regimen and upfront HDCT demonstrated improved outcomes. Our data suggest a minimum of two HDCT cycles with ASCT should be standard of care for patients with RR GCC. Failure of HDCT results in a poor prognosis with only 10% of patients achieving lasting remission with salvage therapy.

Brentuximab vedotin for treatment of non-Hodgkin lymphomas: A systematic review.

BACKGROUND: Brentuximab vedotin (BV) is an antibody-drug conjucate (ADC) comprising a CD30-directed antibody, conjugated to the microtubule-disrupting agent MMAE via a protease cleavable linker. BV is FDA approved for use in relapsed classical Hodgkin lymphoma (HL) and relapsed systemic anaplastic large cell lymphoma (sALCL). There are multiple publications for its utility in other malignancies such as diffuse large B-cell lymphoma (DLBCL), mycosis fungoides (MF), Sézary syndrome (SS), T-cell lymphomas (TCL), primary mediastinal lymphoma (PMBL), and post-transplant lymphoproliferative disorders (PTLD). We believe that BV could potentially provide a strong additional treatment option for patients suffering from NHL. OBJECTIVE: Perform a systematic review on the use of BV in non-Hodgkin lymphoma (NHL) and other CD30+ malignancies in humans. DATA SOURCES: We searched various databases including PubMed (1946-2015), EMBASE (1947-2015), and Cochrane Central Register of Controlled Trials (1898-2015). ELIGIBILITY CRITERIA: Inclusion criteria specified all studies and case reports of NHLs in which BV therapy was administered. INCLUDED STUDIES: A total of 28 articles met these criteria and are summarized in this manuscript. CONCLUSION: Our findings indicate that BV induces a variety of responses, largely positive in nature and variable between NHL subtypes. With additional, properly powered prospective studies, BV may prove to be a strong candidate in the treatment of various CD30+ malignancies.

Robotic Left Ventricular Assist Device Implantation Using Left Thoracotomy Approach in Patients with Previous Sternotomies.

Left ventricular assist devices (LVADs) are commonly used as either a bridge-to-transplant or a destination therapy. The traditional approach for LVAD implantation is via median sternotomy, but many candidates for this procedure have a history of failed cardiac surgeries and previous sternotomy. Redo sternotomy increases the risk of heart surgery, particularly in the setting of advanced heart failure. Robotics facilitates a less invasive approach to LVAD implantation that circumvents some of the morbidity associated with a redo sternotomy. We compared the outcomes of all patients at our institution who underwent LVAD implantation via either a traditional sternotomy or using robotic assistance. The robotic cohort showed reduced resource utilization including length of hospital stay and use of blood products. As the appropriate candidates become elucidated, robotic assistance may improve the safety and cost-effectiveness of reoperative LVAD surgery.