Myeloablative versus Reduced-Intensity Conditioning for Hematopoietic Cell Transplantation in Acute Myelogenous Leukemia and Myelodysplastic Syndromes-Long-Term Follow-Up of the BMT CTN 0901 Clinical Trial.

Several prospective randomized trials comparing conditioning intensity before allogeneic hematopoietic cell transplantation (HCT) have been performed, with conflicting results. Although reduced-intensity conditioning (RIC) leads to lower treatment-related mortality (TRM), this is offset by higher rates of relapse. Long-term follow-up of randomized comparative trials are limited.

Older adults with newly diagnosed high-risk/secondary AML who achieved remission with CPX-351: phase 3 post hoc analyses.

CPX-351, a dual-drug liposomal encapsulation of daunorubicin/cytarabine in a synergistic 1:5 molar ratio, is approved for the treatment of adults with newly diagnosed, therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC). In a pivotal phase 3 study, patients aged 60 to 75 years with newly diagnosed, high-risk/secondary AML were randomized to receive CPX-351 or conventional 7+3 chemotherapy. In the primary endpoint analysis, CPX-351 demonstrated significantly prolonged median overall survival (OS) vs 7+3.

Atezolizumab Plus Chemotherapy for First-Line Treatment of Nonsquamous NSCLC: Results From the Randomized Phase 3 IMpower132 Trial.

Introduction: We report the final results of the phase 3 IMpower132 study evaluating atezolizumab plus carboplatin or cisplatin plus pemetrexed (APP) in patients with nonsquamous NSCLC.

Methods: Chemotherapy-naive patients with stage IV nonsquamous NSCLC without sensitizing EGFR or ALK genetic alterations were randomized in a one-to-one ratio to receive four or six cycles of carboplatin or cisplatin plus pemetrexed (PP) or APP every 3 weeks, followed by maintenance therapy with atezolizumab plus pemetrexed or pemetrexed alone. Co-primary end points were overall survival (OS) and investigator-assessed progression-free survival (PFS).

Class II HLA mismatch improves outcomes following haploidentical transplantation with posttransplant cyclophosphamide.

HLA disparity is the major predictor of outcome following unrelated donor (UD) transplantation, where a single mismatch (mm) at the HLA-A, HLA-B, HLA-C, or HLA-DRB1 locus leads to increased mortality, and mismatching at multiple loci compounds this effect. In contrast, HLA disparity has not been shown to increase mortality in the context of haploidentical transplant using posttransplant cyclophosphamide (PTCy). To better define the consequences of loci-specific HLA mm, we analyzed 208 consecutive patients undergoing haploidentical transplantation for hematologic malignancy using PTCy at our institution (median age, 52 years [range, 19-75 years]; peripheral blood stem cell, 66%; reduced-intensity conditioning, 59%).

Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study.

Background: Lisocabtagene maraleucel (liso-cel) is an autologous, CD19-directed, chimeric antigen receptor (CAR) T-cell product. We aimed to assess the activity and safety of liso-cel in patients with relapsed or refractory large B-cell lymphomas.

Methods: We did a seamless design study at 14 cancer centres in the USA.

Prospective phase 2 trial of ixazomib after nonmyeloablative haploidentical peripheral blood stem cell transplant.

Proteasome inhibition results in extensive immunomodulatory effects that augment natural killer cell cytotoxicity and inhibit aspects of T-cell, B-cell, and dendritic cell function. We performed a phase 2 study that examined the effects of ixazomib for graft-versus-host disease (GVHD) prophylaxis (up to 12 cycles) with posttransplant cyclophosphamide and tacrolimus after standard nonmyeloablative haploidentical donor transplantation (HIDT). Ixazomib was started on day +5 (4 mg on days 1, 8, and 15 of a 28-day cycle), with dose reductions allowed in future cycles for toxicity.

Spinocerebellar Ataxia Patient Perceptions Regarding Reproductive Options.

Background: In vitro fertilization with preimplantation genetic testing is a growing reproductive option for people who want to avoid passing a single-gene condition on to their offspring. The spinocerebellar ataxias are a group of rare, autosomal-dominant neurodegenerative disorders which are strong candidates for the use of this technology.

Objectives: This study aimed to assess knowledge of genetic risk and perceptions of reproductive options in individuals with a diagnosis of spinocerebellar ataxia.

Health-Related Quality of Life With Carboplatin-Paclitaxel or nab-Paclitaxel With or Without Pembrolizumab in Patients With Metastatic Squamous Non-Small-Cell Lung Cancer.

Purpose: In the phase 3 KEYNOTE-407 study, the addition of pembrolizumab to carboplatin-paclitaxel/nab-paclitaxel significantly improved overall survival, progression-free survival, and objective response rate in patients with previously untreated metastatic squamous non-small-cell lung cancer (NSCLC), with little impact on severe toxicity. We present patient-reported outcomes (PROs) from KEYNOTE-407.

Methods: Patients were randomly assigned to receive 4 cycles of pembrolizumab 200 mg or placebo once every 3 weeks plus carboplatin plus paclitaxel or nab-paclitaxel, followed by pembrolizumab or placebo for an additional 31 cycles.

Real-world outcomes of unselected elderly acute myeloid leukemia patients referred to a leukemia/hematopoietic cell transplant program.

Due to perceived intolerance, many elderly AML patients do not receive therapy, and few are considered for hematopoietic cell transplantation (HCT). To better understand "real-world" outcomes, 323 consecutive AML patients ≥ 60 years referred from 2009 to 2017 were evaluated (median age 70 [60-88] years); favorable (fav) in 48 (15%), intermediate (int) in 112 (35%) and poor risk in 161 (50%). Remission induction therapy, either intensive chemotherapy (IC, n = 205) or hypomethylating agents (HMA, n = 57), was given to all but 61 (19%) patients.

Prognostic Role of Androgen Receptor in Triple Negative Breast Cancer: A Multi-Institutional Study.

Background: The androgen receptor (AR) has emerged as a potential therapeutic target for AR-positive triple-negative breast cancer (TNBC). However, conflicting reports regarding AR's prognostic role in TNBC are putting its usefulness in question. Some studies conclude that AR positivity indicates a good prognosis in TNBC, whereas others suggest the opposite, and some show that AR status has no significant bearing on the patients' prognosis.

Accuracy of estimated total liver volume formulas before liver resection.

Background: Future remnant liver volume is used to predict the risk for liver failure in patients who will undergo major liver resection. Formulas to estimate total liver volume based on biometric data are widely used to calculate future remnant liver volume; however, it remains unclear which formula is most accurate. This study evaluated published estimate total liver volume formulas to determine which formula best predicts the actual future remnant liver volume based on measurements in a large number of patients who underwent associating liver partition and portal vein ligation for staged hepatectomy surgery.

Overall survival and histology-specific subgroup analyses from a phase 3, randomized controlled study of trabectedin or dacarbazine in patients with advanced liposarcoma or leiomyosarcoma.

Background: We performed a randomized phase 3 study of trabectedin versus dacarbazine in previously-treated patients with liposarcoma/leiomyosarcoma (LPS/LMS).

Methods: Patients were randomized 2:1 to trabectedin (n = 384) or dacarbazine (n = 193) administered intravenously every 3 weeks. The primary objective was overall survival (OS).

Efficacy and Safety of Ribociclib With Letrozole in US Patients Enrolled in the MONALEESA-2 Study.

Background: In the Mammary Oncology Assessment of LEE011's (Ribociclib's) Efficacy and Safety (MONALEESA-2) study, combination treatment with the selective inhibitor of cyclin-dependent kinases 4/6 ribociclib with letrozole significantly improved progression-free survival (PFS) versus letrozole alone in postmenopausal women with hormone receptor-positive HR/HER2 advanced breast cancer (ABC). Herein we present results from the subset of US patients enrolled in MONALEESA-2.

Patients And Methods: Postmenopausal women with HR/HER2 ABC without previous treatment for advanced disease were randomized (1:1) to ribociclib 600 mg/d (3 weeks on/1 week off) with letrozole 2.

Chimeric Antigen Receptor T-Cells: The Future is Now.

The immune system acting via cancer immune-surveillance is considered a potential target for improving outcomes among some malignancies. The ability to harness immune cells, engineer them and educate them to target cancer cells has changed the paradigm for treating non-Hodgkin's lymphomas (NHL) and acute lymphoblastic leukemia (ALL). Chimeric antigen receptor (CAR) T-cell therapy has shown remarkable anti-tumor activity against refractory B cell malignancies.

A phase 2 study of glembatumumab vedotin, an antibody-drug conjugate targeting glycoprotein NMB, in patients with advanced melanoma.

Background: Glembatumumab vedotin is an antibody-drug conjugate that produced preliminary clinical activity against advanced melanoma in a phase 1 dose-escalation trial. The objective of the current study was to investigate further the antitumor activity of glembatumumab vedotin at the recommended phase 2 dose in heavily pretreated patients with melanoma.

Methods: This single-arm, phase 2 study enrolled patients with stage IV melanoma who were refractory to checkpoint inhibition and to B-raf proto-oncogene, serine/threonine kinase (BRAF)/mitogen-activated protein kinase kinase (MEK) inhibition (in the presence of a BRAF valine mutation at codon 600).

Long-term survival in patients with advanced non-small-cell lung cancer treated with atezolizumab versus docetaxel: Results from the randomised phase III OAK study.

Background: Atezolizumab (anti-programmed death-ligand 1 [PD-L1]) received approval from the US Food and Drug Administration and European Medicines Agency for previously treated advanced non-small-cell lung cancer based on OAK-a randomised, phase III trial that showed significantly improved survival with atezolizumab versus docetaxel regardless of PD-L1 expression. With longer follow-up, we summarised the characteristics of long-term survivors (LTSs).

Methods: In OAK (NCT02008227), patients were randomised 1:1 to receive atezolizumab or docetaxel until loss of clinical benefit or disease progression, respectively.

The Effect of Body Weight Support on Energy Expenditure in an Individual With High-Level Lower Extremity Amputation.

Background: High-level lower extremity amputation (HLLEA) has significant impact on an individual's ability to ambulate and maintain cardiovascular fitness for extended periods of time.

Objective: The purpose of this study was to evaluate whether body weight support (BWS) would improve energy efficiency in an individual with HLLEA to achieve appropriate target cardiovascular intensity for aerobic training.

Design: This was an exploratory single-subject study.

Patient-Reported Outcomes in OAK: A Phase III Study of Atezolizumab Versus Docetaxel in Advanced Non-Small-cell Lung Cancer.

Background: The randomized phase III OAK (a study of atezolizumab compared with docetaxel in participants with locally advanced or metastatic non-small-cell lung cancer [NSCLC] who have failed platinum-containing therapy) trial investigated the anti-programmed cell death ligand 1 (PD-L1) antibody atezolizumab for advanced or metastatic, previously treated, NSCLC. Atezolizumab significantly improved overall survival (OS) compared with docetaxel (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.

Delineating a new feature of constitutional mismatch repair deficiency (CMMRD) syndrome: breast cancer.

Constitutional mismatch repair deficiency (CMMRD) syndrome is a rare autosomal recessive hereditary cancer condition, characterized by an exceptionally high risk of cancer, a propensity for childhood malignancies, and cutaneous features reminiscent of neurofibromatosis type 1 (NF1). We report on two sisters originally suspected of having CMMRD syndrome due to their history of colonic polyps and NF1 associated skin findings, both were subsequently found to have biallelic MSH6 mutations. After years of CMMRD syndrome follow-up, the proband was diagnosed with breast cancer at age 29, while her sister was diagnosed with a glioblastoma at age 27.

Amplified centrosomes and mitotic index display poor concordance between patient tumors and cultured cancer cells.

Centrosome aberrations (CA) and abnormal mitoses are considered beacons of malignancy. Cancer cell doubling times in patient tumors are longer than in cultures, but differences in CA between tumors and cultured cells are uncharacterized. We compare mitoses and CA in patient tumors, xenografts, and tumor cell lines.