Immune signatures associated with improved progression-free and overall survival for myeloma patients treated with AHSCT.

Multiple therapeutic options exist for multiple myeloma (MM), including autologous hematopoietic stem cell transplantation (AHSCT). Measurement of minimal residual disease (MRD) and immune reconstitution is rapidly becoming an integral part of the care of MM patients. We investigated comprehensive immune profiling (IP) associated with progression-free survival (PFS) and overall survival (OS). From August 2007 to January 2014, 101 consecutive MM patients underwent peripheral blood IP and marrow MRD testing before and approximately 100 days after AHSCT. Higher pre-AHSCT CD19+ B-cell counts correlated with improved 2-year PFS (83% [highest quartile] vs 53% [lowest quartile]; P = .01) and OS (93% [highest quartile] vs 63% [lowest quartile]; P = .0003). This effect was seen primarily in patients with MRD-positive marrow tests. Higher γδ T-cell counts post-AHSCT correlated with improved 2-year PFS (65% [highest quartile] vs 45% [lowest quartile]; P = .02) and OS (89% [highest quartile] vs 65% [lowest quartile]; P = .01). Higher CD4+ central memory (CM) cell counts post-AHSCT were associated with improved 2-year OS (95% [upper quartile] vs 47% [lowest quartile]; P = .0003) but not PFS. The higher γδ T-cell and CD4+ CM-cell count associations were primarily observed in MRD-negative patients post-AHSCT and in patients not receiving maintenance therapy. This proof-of-concept study demonstrates that IP before and after AHSCT can be of complementary prognostic value for depth of response. Maintenance therapy seems to overcome negative IP. IP and MRD should be measured in clinical trials of maintenance therapy with novel agents post-AHSCT for MM to confirm their utility for prognosis and management.

A phase II study of high-dose cetuximab plus irinotecan in colorectal cancer patients with KRAS wild-type tumors who progressed after standard dose of cetuximab plus irinotecan.

OBJECTIVES: We conducted a phase II clinical trial of high-dose cetuximab plus irinotecan in KRAS wild-type patients who progressed on standard-dose cetuximab plus irinotecan. METHODS: Patients who progressed within 4 weeks from receiving a minimum of 6 weeks of standard-dose cetuximab plus irinotecan were included in this study. Cetuximab was administered at 500 mg/m(2)/week and irinotecan was administered at the same dose/schedule on which each individual patient had previously progressed. The study was closed early after having met its primary end point. RESULTS: Twenty patients were treated. The regimen was found to be efficacious, with 9 patients achieving disease control lasting more than 12 weeks. The median progression-free survival and overall survival were 2.8 and 6.6 months, respectively. The toxicity profile was favorable, with the exception of grade 3-4 hypomagnesemia which was noted in 25% of patients. CONCLUSIONS: High-dose cetuximab plus irinotecan rechallenge can re-elicit clinical benefits in patients who have previously failed cetuximab plus irinotecan treatment. The clinical benefits are modest and may be related to cetuximab rechallenge rather than cetuximab dose escalation.

Intensive radiographic and biomarker surveillance in stage II and III colorectal cancer.

OBJECTIVE: The objective of this study was to determine the rate of salvage resections in patients with stage II and III colorectal cancer following intensive surveillance in a comprehensive cancer center. METHODS: Patients with stage II and III colorectal cancer with a minimum follow-up of 3 years were included. Carcinoembryonic antigen was obtained every 3 months for 2 years and then every 6 months for years 3-5. CT scans of the chest, abdomen and pelvis were performed every 6 months for 2 years and then yearly for years 3-5. Colonoscopy was performed at year 1 and then every 3 years. RESULTS: One hundred and seventy-seven patients were followed for a median of 60 months; 44 patients were diagnosed with recurrent disease. CT was the first sign of recurrence in 68% of patients. Carcinoembryonic antigen test was normal in 20 patients (45%) at the time of disease recurrence. Twenty-five patients (57%) with recurrent disease underwent curative-intent resection, 12 of whom are still cancer free at a median follow-up of 81 months. CONCLUSIONS: In this retrospective study, intensive radiographic screening was associated with a high salvage resection rate, which led to favorable clinical outcomes. Randomized clinical trials are urgently needed to define the optimal duration and schedule of radiographic screening in stage II and III colorectal cancer.

Quantitative methodology using CT for predicting survival in patients with metastatic colorectal carcinoma: a pilot study.

OBJECTIVE: To develop a methodology which quantifies multiple changing lesion features resulting in an optimized computed tomography (CT) response score (CRS) for prediction of overall survival (OS) in response to treatment for metastatic colorectal carcinoma (MCRC). SUBJECTS AND METHODS: This Health Insurance Portability and Accountability Act-compliant, institutional review board-approved retrospective study evaluated multiple changing imaging findings and their correlation with OS with a new methodology comparing the baseline and first post-treatment CT scans in 38 MCRC patients on last-line chemotherapy (cetuximab and irinotecan). Tumor size/enhancement changes and interval development of new lesions were quantified with either Likert-type scales (all parameters) or Response Evaluation Criteria in Solid Tumors (RECIST) (size change only). The most predictive parameters for OS were used to generate the CRS with an overall range of -3 (complete disappearance) to +2 (definite tumor increase). The Cox Hazard Ratio was used to assess prediction of survival. Reader agreement was evaluated by the kappa statistic. RESULTS: Tumor size was the best predictor of OS using the Likert-type scale or RECIST. The CRS was not improved combining size change with other parameters. Use of the Likert-type scale resulted in predicting OS with a Cox hazard ratio of 1.697 (P=.0004) and good agreement (kappa=0.73, 95% CI=0.41-1.10) between observers with no significant difference using RECIST. CONCLUSION: The methodology produces a CRS for MCRC predicting OS resulting from therapy which expands standard RECIST guidelines to allow critical evaluation of multiple additional imaging parameters. Size change alone was found to be the best parameter of those considered in terms of maximizing agreement and prediction of OS.

A case of 5-fluorouracil-induced acute psychosis.

5-Fluorouracil (5-FU) is a chemotherapeutic agent commonly used in a number of solid malignancies, including colorectal cancer. Herein, we report the first case of 5-FU-induced psychosis. Psychosis occurred after the first 2 cycles of 5-FU, oxaliplatin, leucovorin, plus bevacizumab and recurred upon rechallenge with further 5-FU and leucovorin.

Spontaneous regression of colorectal cancer metastatic to retroperitoneal lymph nodes.

Spontaneous remissions have been reported in solid tumors such as melanoma and renal cell cancer. However, spontaneous remissions in colon cancer have not been previously radiographically confirmed. A case of colon cancer metastatic to the retroperitoneal lymph nodes that exhibited a durable spontaneous regression is reported. The exact trigger of this phenomenon has not been elucidated; however, an antitumor immune response is the most likely explanation. The identification and characterization of similar cases would probably result in defining a patient population that can be followed by observation and may result in the development of novel therapeutic strategies.