Alliance researchers to Present Novel Data at 2016 ASH Meeting

The Alliance for Clinical Trials in Oncology presented an array of novel data from many of its hematology studies during the 58th American Society of Hematology (ASH) Annual Meeting and Exposition held in San Diego, CA. Many of these data will help change the delivery of hematologic cancer care or help elucidate the underlying cause and effect relationships seen in this field.

Here is a summary of the Alliance trials.

Alliance A151611*
Toxicities and Related Outcomes of Elderly Patients (pts) (≥65 Years) with Hematologic Malignancies in the Contemporary Era (Alliance A151611)
Tallarico M, Foster J, Seisler D, Lafky J, Hurria A, Jatoi A, Cohen HJ, Muss H, Bartlett NL, Cheson B, Jung SH, Byrd JC, Leonard JP, Nabhan C
Blood 128:536; 2016
Synopsis: In 65-year-old patients with chronic lymphocytic leukemia or non-Hodgkin lymphoma, Alliance researchers identified several clinical and disease-related factors as potential predictors of developing grade 3 and/or 4 hematologic and non-hematologic toxicities. A prognostic model is being constructed to predict toxicities in these patients to guide management and monitoring. The impact of these toxicities on outcomes is being analyzed.
*Dr. Tallarico has received the 2016 ASH Abstract Achievement Award and Outstanding Abstract Achievement Award for this abstract. Each year, ASH offers merit-based awards in the amount of $500 to trainees with high-scoring annual meeting abstracts. Abstract Achievement Awards (formerly Travel Awards) are intended for those trainees who are chosen to present an abstract, of which they are the first or senior author and presenter, at the ASH annual meeting. Outstanding Abstract Achievement Awards (formerly Merit Awards) are provided to abstract presenters with the highest scoring abstracts of which they are the first author in each of the following categories: undergraduate student, medical student, graduate student, resident physician, and post-doctoral fellow (MD or PhD). In addition to the $500 honorarium, Outstanding Abstract Achievement Award winners receive annual meeting travel reimbursement.

Alliance 151614
Impact of the Timing of Complete Remission and Transplantation on Estimates of Event-Free Survival in Acute Myeloid Leukemia
Yin J, Laplant BR, Uy GL, Marcucci G, Blum W, Larson RA, Stone RM, Mandrekar S
Blood 128:214, 2016
Synopsis: Although relapse and death are firm endpoints, the determination of failure to achieve complete remission (CR) is not consistent across studies. While there is minimal impact of censoring at hematopoietic cell transplantation (HCT) on event-free survival (EFS) estimates, the median EFS estimates differed considerably based on the timing of CR used to define induction failure, with the magnitude of difference being large enough in most cases (observed range: 14% to >100%) to lead to incorrect conclusions about efficacy in a single-arm trial if the trial definition was not consistent with the definition used for the historical control. The timing of CR should be carefully examined in the historical control data used to guide the design of the next trial.

CALGB (Alliance) 10701
A Phase II Study of Dasatinib and Dexamethasone As Primary Therapy Followed By Hematopoietic Cell Transplantation for Adults with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: CALGB Study 10701 (Alliance)
Wieduwilt MJ, Yin J, Wetzler M, Uy GL, Powell BL, Kolitz JE, Liedtke M, Stock W, Beumer JH, Mattison RJ, Halvorson A, Devine SM, Smith S, Stone RM, Larson RA
Blood 128:2782, 2016
Synopsis: Dasatinib with dexamethasone yields complete remission (CR) rates comparable to those reported with tyrosine kinase inhibitors combined with conventional chemotherapy. Post-remission therapy with reduced-intensity allogeneic hematopoietic cell transplantation (HCT), autologous HCT, or chemotherapy followed by dasatinib maintenance is feasible. Survival follow up is maturing. For more information about the trial, visit https://clinicaltrials.gov/ct2/show/NCT01256398

CALGB (Alliance) 50303
Phase III Randomized Study of R-CHOP Versus DA-EPOCH-R and Molecular Analysis of Untreated Diffuse Large B-Cell Lymphoma: CALGB/Alliance 50303
Wilson WH, Sin-Ho J, Pitcher BN, Hsi ED, Friedberg J, Cheson B, Bartlett NL, Smith S, Johnston NW, Kahl BS, Staudt LM, Blum K, Abramson J, Press OW, Fisher RI, Richards KL, Schoder H, Chang JE, Zelenetz AD, Leonard JP
Blood 128:469, 2016
Synopsis: There was no difference in event-free survival or overall survival between chemotherapy regimens R-CHOP and DA-EPOCH-R when considering all patients. DA-EPOCH-R showed increased toxicity consistent with higher dose-intensity but not increased grade 5 toxicity. Compared to R-CHOP, more patients on DA-EPOCH-R did not complete treatment, which may reflect patterns of care or toxicity. Due to the clinical and genetic diversity of diffuse large b-cell lymphoma (DLBCL), subset analyses are necessary to determine the effect of central nervous system (CNS) relapse, germinal center B-cell (GCB) and activated B-cell (ABC) subtypes, age and International Prognostic Index (IPI) on outcomes of the two arms. These data do not address the efficacy of these regimens in primary mediastinal B-cell lymphoma (PMBL) or MYC+ DLBCL due to their low frequency, and where more dose-intense regimens appear to be important. Full molecular analyses are ongoing. For more information about the trial, visit https://clinicaltrials.gov/ct2/show/NCT00118209

CALGB (Alliance) 50402, 50701, 50803
Early Relapse of Follicular Lymphoma after Rituximab-Based Biologic Doublet Upfront Therapy Is Associated with Increased Risk of Death: A Combined Analysis from CALGB Studies 50402, 50701 and 50803 (Alliance)
Lansigan F, Barak I, Pitcher BN, Jung SH, Cheson B, Czuczman MS, Grant BW, Martin P, Hsi ED, Schoder H, Smith SE, Bartlett NL, Leonard JP, Blum K
Blood 128:2953, 2016
Synopsis: Early relapse within two years after diagnosis in patients receiving front-line rituximab-based biologic non-cytotoxic therapy is associated with an increased risk of death. These data are similar to previous findings in patients treated with the chemotherapy regimen R-CHOP from the National LymphoCare study, suggesting that the adverse survival of patients with early progression of disease may be independent of systemic treatment modality. Novel clinicopathological approaches are needed at diagnosis to identify patients who are likely to have unfavorable outcomes, and for whom biologic doublets are efficacious.

 

For other articles in the December issue of the Alliance E-News newsletter, see below.