Citations 2
Randomized trial of 10 days of decitabine ± bortezomib in untreated older patients with AML: CALGB 11002 (Alliance)
Mandrekar, Sumithra J. , Laumann, Kristina, Walker, Alison R. , Wang, Eunice S. , Kolitz, Jonathan E. , Powell, Bayard L., Attar, Eyal C. , Bloomfield, Clara D. , Kohlschmidt, Jessica, Mrózek, Krzysztof , Garraway, Levi A. , Jané‐Valbuena, Judit , Baltay, Michele , Tracy, Adam , Marcucci, Guido , Stone, Richard M. , Wang, Eunice S. , Roboz, Gail J. , Desai, Pinkal , Stock, Wendy , Hassane, Duane C. , Larson, Richard A.
Blood Advances | December 19, 2018 | Volume: 2 | Issue: 24 | Pages: 3608-3617
10.1182/bloodadvances.2018023689
Abstract Novel treatment strategies are needed for older patients with acute myeloid leukemia (AML). This randomized phase 2 trial compared the efficacy and safety of 20 mg/m2 of IV decitabine on days 1 to 10 alone (arm A) with those of 1.3 mg/m2 of subcutaneous bortezomib (arm B) on days 1, 4, 8, and 11 for up to 4 10-day cycles followed by monthly 5-day cycles. Previously untreated AML patients age ≥60 years (excluding those with FLT3 mutations and favorable-risk cytogenetics) without restrictions in performance status (PS) or organ function were eligible. Median age was 72.4 years (range, 60.5-92.3 years); 31 patients (19%) had baseline PS ≥2, 35 (22%) had an antecedent hematological disorder, 58 had (39%) adverse cytogenetics, and 7 (5%) and 23 (14%) had abnormal cardiac or renal function. There were no statistically significant differences in overall survival (OS) or responses between the 2 treatment arms. The overall response rate (complete remission + complete remission with incomplete blood count recovery) was 39% (n = 64), with median OS of 9.3 months. Nineteen responders (31%) underwent allogeneic stem cell transplantation. The most common adverse event was febrile neutropenia, and there were no unexpected toxicities. Adding bortezomib to decitabine did not improve outcomes, but responses were better than those in previous trials using 5-day decitabine cycles. This trial was registered at www.clinicaltrials.gov as #NCT01420926.
Genomic correlates of response to immune checkpoint therapies in clear cell renal cell carcinoma
Miao, Diana , Margolis, Claire A. , Gao, Wenhua , Voss, Martin H. , Li, Wei , Martini, Dylan J. , Norton, Craig, Bossé, Dominick , Wankowicz, Stephanie A. , Cullen, Dana, Horak, Christine E., Wind‐Rotolo, Megan , Tracy, Adam , Giannakis, Marios , Hodi, F. Stephen , Drake, Charles G. , Ball, Mark W. , Hellmann, Matthew D. , Ho, Thai H. , Kaelin, William G. , Choueiri, Toni K. , Hodi, Frank Stephen , Allaf, Mohamad E , Snyder, Alexandra , Hellmann, Matthew D , Ho, Thai , Motzer, Robert J , Signoretti, Sabina , Kaelin, William G , Choueiri, Toni K , Van Allen, Eliezer M , Voss, Martin H , Motzer, Robert J.
Science | January 4, 2018 | Volume: 359 | Issue: 6377 | Pages: 801-806
SNF'ing out antitumor immunity Immune checkpoint inhibitors induce durable tumor regressions in some, but not all, cancer patients. Understanding the mechanisms that determine tumor sensitivity to these drugs could potentially expand the number of patients who benefit (see the Perspective by Ghorani and Quezada). Pan et al. discovered that tumor cells in which a specific SWI/SNF chromatin remodeling complex had been experimentally inactivated were more sensitive to T cell–mediated killing. The cells were more responsive to interferon-γ, leading to increased secretion of cytokines that promote antitumor immunity. Miao et al. examined the genomic features of tumors from patients with metastatic renal cell carcinoma who had been treated with immune checkpoint inhibitors. Tumors harboring inactivating mutations in PBRM1 , which encodes a subunit of the same SWI/SNF complex, were more likely to respond to the drugs. Science , this issue p. 770 , p. 801 ; see also p. 745