High risk of relapse with intermediate dose cytarabine for consolidation in young favourable-risk acute myeloid leukaemia patients following induction with 7+3: a retrospective multicentre analysis and critical review of the literature.

Following the 2017 European LeukemiaNet (ELN) guidelines, we changed our practice from using high-dose cytarabine (HIDAC-3 g/m2 q12h-D1,3,5) to intermediate-dose cytarabine (IDAC-1·5 g/m2 q12h-D1,3,5/D1-3) for consolidation in young(<60 years) favourable-risk acute myeloid leukaemia (AML) patients. We assessed the clinical impact of this practice change. Of 80 patients, 51 received HIDAC prior to the protocol change, and subsequently, 29 received IDAC. The three-year risk of relapse was significantly higher with IDAC [61%; 95% confidence interval (CI) 40-82] compared with HIDAC (22%; 10-34), P < 0·01. Our findings suggest HIDAC, rather than IDAC, is the preferred dose for single-agent cytarabine consolidation in young, favourable-risk AML following 7+3 induction.

Intensive induction regimens after deferring initial therapy for mantle cell lymphoma are not associated with improved survival.

INTRODUCTION: While most patients with mantle cell lymphoma (MCL) receive therapy shortly after diagnosis, a subset of patients with indolent-behaving disease can safely defer treatment. In this subgroup, we evaluated the importance of treatment intensity in patients with MCL who defer initial therapy. METHODS: Out of 1134 patients with MCL from 12 academic centers, we analyzed 219 patients who initiated therapy at least 90 days after diagnosis. Patients who received induction with high-dose cytarabine and/or autologous stem cell transplantation (ASCT) in first remission were considered to have received intensive therapy (n = 88) while all other approaches were non-intensive (n = 131). RESULTS: There was no difference in progression-free (PFS; P = .224) or overall survival (OS; P = .167) in deferred patients who received non-intensive vs. intensive therapy. Additionally, univariate and multivariate Cox proportional hazards models were performed for PFS and OS. Treatment at an academic center (HR 0.43, P = .015) was associated with improved OS in both univariate and multivariate models, while intensity of treatment was not associated with improved OS in either model. CONCLUSIONS: These results indicate that intensified initial treatment is not associated with improved survival after deferring initial therapy, although prospective studies are needed to determine which of these patients with MCL may benefit from intensive therapy.

Multi-center analysis of practice patterns and outcomes of younger and older patients with mantle cell lymphoma in the rituximab era.

Clinical outcomes and predictors of survival in patients with newly diagnosed mantle cell lymphoma (MCL) treated in the rituximab era (2000-2015) at 12 US academic centers were assessed to identify determinants of survival across age groups. Objectives were to characterize and compare practice patterns, outcomes and prognostic factors for survival in younger patients (age < 65) and older patients (age ≥ 65 years). Among 1162 patients included, 697 were younger and 465 were older. In younger patients, 2-year progression free survival (PFS) and overall survival (OS) rates were 79% and 92% respectively; blastoid histology, ECOG ≥ 2, and lack of maintenance rituximab (MR) remained statistically relevant to poor OS on univariate analysis (UVA) and multivariate analysis (MVA). In older patients, 2-year PFS and OS rates were 67% and 86% respectively; lack of maintenance rituximab remained significantly associated with inferior PFS and OS on UVA and MVA (p < 0.001). Two-year PFS rates were 79%, and 67% and 2-year OS rates were 92% and 86% for ages < 65 and ≥ 65 respectively (p < 0.001). First-line high-dose cytarabine exposure and/or MR lessened the negative impact of age on survival. Taken collectively, survival outcomes for older patients remain inferior to those of younger patients in the rituximab era. However, maintenance rituximab and potentially high-dose cytarabine-based induction can mitigate the negative impact of age on survival.

Outcomes of patients with blastoid and pleomorphic variant mantle cell lymphoma.

Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma; data indicate that blastoid and pleomorphic variants have a poor prognosis. We report characteristics and outcomes of patients with blastoid/pleomorphic variants of MCL. We retrospectively studied adults with newly diagnosed MCL treated from 2000 to 2015. Primary objectives were to describe progression-free survival (PFS) and overall survival (OS). Secondary objectives included characterization of patient characteristics and treatments. Of the 1029 patients with MCL studied, a total of 207 neoplasms were blastoid or pleomorphic variants. Median follow-up period was 82 months (range, 0.1-174 months); median PFS was 38 months (95% confidence interval [CI], 28-66) and OS was 68 months (95% CI, 45-96). Factors associated with PFS were receipt of consolidative autologous hematopoietic transplantation (auto-HCT; hazard ratio [HR], 0.52; 95% CI, 0.31-0.80; P < .05), MCL International Prognostic Index (MIPI) intermediate (HR, 2.3; 95% CI, 1.2-4.3; P < .02) and high (HR, 3.8; 95% CI, 2.0-7.4; P < .01) scores, and complete response to induction (HR, 0.29 (95% CI, 0.17-0.51). Receipt of auto-HCT was not associated with OS (HR, 0.69; 95% CI, 0.41-1.16; P = .16) but was associated with MIPI intermediate (HR, 5.7; 95% CI, 2.5-13.2; P < .01) and high (HR, 10.8; 95% CI, 4.7-24.9; P < .01) scores. We report outcomes in a large cohort of patients with blastoid/pleomorphic variant MCL. For eligible patients, receipt of auto-HCT after induction was associated with improved PFS but not OS. Higher MIPI score and auto-HCT ineligibility were associated with worse survival.

Early relapse identifies MCL patients with inferior survival after intensive or less intensive frontline therapy.

Although an expanding array of effective treatments has resulted in recent improvement in survival of patients with mantle cell lymphoma (MCL), outcomes remain heterogeneous, and identification of prognostic factors remains a priority. We assessed the prognostic impact of time to progression of disease (POD) after first-line therapy among 455 patients with relapsed MCL. Patients were categorized by duration of first remission as PRF/POD6, defined as progressive disease during induction or POD within 6 months of diagnosis (n = 65; 14%); POD6-24, defined as POD between 6 and 24 months after diagnosis (n = 153; 34%); and POD>24, defined as POD >24 months after diagnosis (n = 237; 53%). The median overall survival from POD (OS2) was 1.3 years (95% confidence interval [CI], 0.9-2.4) for patients with PRF/POD6, 3 years (95% CI, 2-6.8) for those with POD6-24, and 8 years (95% CI, 6.2-NR) for those with POD>24. Median OS2 was inferior in patients with early POD (defined as PRF/POD6 or POD6-24) after both intensive and less intensive frontline treatment. The prognostic performance of time until POD was replicated in an independent cohort of 245 patients with relapsed MCL, with median OS2 of 0.3 years (95% CI, 0.1-0.5) for PRF/POD6, 0.8 years (95% CI, 0.6-0.9) for POD6-24, and 2.4 years (95% CI 2.1-2.7) for POD>24. Early POD is associated with inferior OS2 in patients with relapsed MCL, identifying a high-risk population for future prospective studies.

Deep and Prolonged Response to Aurora A Kinase Inhibitor and Subsequently to Nivolumab in MYCL1-Driven Small-Cell Lung Cancer: Case Report and Literature Review.

Small-cell lung carcinoma (SCLC) is one of the most aggressive solid tumors, and the prognosis has not improved significantly in 25 years. Despite a recent understanding of the genomic aberrations seen in SCLC, these insights have not led to any breakthroughs in treatment. We present a patient with SCLC harboring a novel MYCL1 fusion protein who experienced a prolonged disease course due to the use of Aurora A kinase inhibitor and subsequently nivolumab. MYC family genes are master regulators of several cellular pathways including proliferation, differentiation, and apoptosis and recently have been shown to be involved in tumor immune evasion. Large studies have shown that a significant proportion of patients with SCLC have amplification or overexpression of MYC family genes. Preclinical data have exposed vulnerability of MYC-driven tumors to Aurora kinase inhibitors, bromodomain and extraterminal domain inhibitors, and recently to immune checkpoint blockers. Further studies using these agents with selective enrolling of patients with MYC-altered tumors are warranted to exploit these vulnerabilities.

Impact of adjuvant chemotherapy on outcomes in appendiceal cancer.

BACKGROUND: The impact of using adjuvant chemotherapy following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with appendiceal adenocarcinoma is not known. The aim of this study was to assess the impact of adjuvant chemotherapy following complete cytoreduction in patients with appendiceal adenocarcinoma. METHODS: Retrospective medical record review of all patients with appendiceal adenocarcinoma treated at our institution between 2006 and 2015. Kaplan-Meier plots were used to summarize overall survival (OS) and relapse-free survival over time, and log-rank tests and Cox proportional hazards models were used to test for differences in survival between groups. RESULTS: A total of 103 patients with appendiceal adenocarcinoma received care at our institution during the study period. Complete cytoreduction (cytoreductive score 0-1) was achieved in 68 patients (66%). Of these 68 patients, 26 received adjuvant chemotherapy. The most common regimens were capecitabine (n = 11), capecitabine plus oxaliplatin (n = 7), and 5-FU plus oxaliplatin (n = 6). Tumor histopathology and grade, and the ability to achieve complete cytoreduction were significant predictors of overall survival. The median OS for non-low-grade and well-differentiated tumor patients who received adjuvant chemotherapy following complete cytoreduction was 9.03 years, compared to 2.88 years for patients who did not receive adjuvant chemotherapy (P = .02). Among low-grade and well-differentiated tumor patients who underwent complete cytoreduction, there was no statistically significant difference in OS between those who received adjuvant chemotherapy and those who did not. CONCLUSION: Adjuvant chemotherapy seems to have benefit in appendiceal cancer patients with non-low-grade or well-differentiated tumor type but not in low-grade or well-differentiated tumors.

Survival Outcomes of Younger Patients With Mantle Cell Lymphoma Treated in the Rituximab Era.

PURPOSE: Mantle cell lymphoma (MCL) is a B-cell lymphoma characterized by cyclin D1 expression. Autologous hematopoietic cell transplantation (AHCT) consolidation after induction chemotherapy is often used for eligible patients; however, the benefit remains uncertain in the rituximab era. Herein we retrospectively assessed the impact of AHCT consolidation on survival in a large cohort of transplantation-eligible patients age 65 years or younger. PATIENTS AND METHODS: We retrospectively studied transplantation-eligible adults age 65 years or younger with newly diagnosed MCL treated between 2000 and 2015. The primary objective was to assess for improved progression-free survival (PFS) with AHCT consolidation and secondarily to assess for improved overall survival (OS). Cox multivariable regression analysis and propensity score-weighted (PSW) analysis were performed. RESULTS: Data were collected from 25 medical centers for 1,254 patients; 1,029 met inclusion criteria. Median follow-up for the cohort was 76 months. Median PFS and OS were 62 and 139 months, respectively. On unadjusted analysis, AHCT was associated with improved PFS (75 v 44 months with v without AHCT, respectively; P < .01) and OS (147 v 115 months with v without AHCT, respectively; P < .05). On multivariable regression analysis, AHCT was associated with improved PFS (hazard ratio [HR], 0.54; 95% CI, 0.44 to 0.66; P < .01) and a trend toward improved OS (HR, 0.77; 95% CI, 0.59 to 1.01; P = .06). After PSW analysis, AHCT remained associated with improved PFS (HR, 0.70; 95% CI, 0.59 to 0.84; P < .05) but not improved OS (HR, 0.87; 95% CI, 0.69 to 1.1; P = .2). CONCLUSION: In this large cohort of younger, transplantation-eligible patients with MCL, AHCT consolidation after induction was associated with significantly improved PFS but not OS after PSW analysis. Within the limitations of a retrospective analysis, our findings suggest that in younger, fit patients, AHCT consolidation may improve PFS.

Cardiac Imaging Methods for Chemotherapy-related Cardiotoxicity Screening and Related Radiation Exposure: Current Practice and Trends.

BACKGROUND: Radiation exposure is a serious concern with usage of serial multigated acquisition (MUGA) scans (7.8mSv/study) for chemotherapy-related cardiotoxicity (CRC) screening. The current practice with respect to the imaging modalities chosen for cardiotoxicity screening and related radiation exposure has not been studied. MATERIALS AND METHODS: We performed a serial cross-sectional study from 2011 to 2014, evaluating the relative usage of the three imaging modalities for CRC screening. RESULTS: MUGA scan usage decreased from 30.4% to 16.7%, echocardiogram (Echo) utilization increased from 68.7% to 80.4% and cardiac magnetic resonance (CMR) usage increased from 0.9% to 2.9% in the 4-year period. Estimated total radiation exposure and secondary cancer risk can increase significantly in certain subgroups when MUGA scan is employed for serial cardiac imaging. CONCLUSION: Increased awareness of radiation risks from MUGA, as well as increasing focus on early detection of cardiotoxicity using Echo and CMR, are possible reasons behind the observed trends.

Recurrent pleural effusions and cardiac tamponade as possible manifestations of pseudoprogression associated with nivolumab therapy- a report of two cases.

BACKGROUND: Checkpoint inhibitors are a class of agents that employ host's adaptive immune defenses in fighting cancer. With many new indications and several ongoing clinical trials in a variety of malignancies, the usage of these agents is set to increase significantly. One of the key challenges patients and physicians face while using these drugs is with the appropriate assessment of response to therapy. CASE PRESENTATION: We are reporting two patients with lung cancer who were treated with nivolumab and experienced rapidly accumulating recurrent pleural effusions requiring multiple thoracenteses (6 and 4 times each for patient 1 and 2 respectively) with in the first few weeks of initiation of therapy and also developed pericardial effusion with cardiac tamponade requiring pericardiocentesis. Both patients had prior history of malignant spread to pleural and pericardial space in their disease course. Therapy was continued in the first patient with spontaneous resolution of effusions after 8 weeks and the disease showed near complete response to treatment on imaging at 16 weeks. Second patient declined to continue further treatment with nivolumab after 3 cycles due to recurrent effusions and cardiac tamponade, although there was some evidence of clinical response at discontinuation. CONCLUSIONS: Patients with history of malignant involvement of visceral spaces should be monitored closely for rapidly accumulating effusions and particularly for cardiac tamponade, after initiation of therapy with nivolumab. This presentation could represent pseudoprogression, and continuation of therapy with close monitoring is prudent as long as effusions are manageable and there is no definitive evidence of progression elsewhere.