The oncology community will soon be seeing the much-anticipated data being presented at the 2018 ASCO Annual Meeting. More than 5000 submitted abstracts will showcase findings across tumor types, which include practice-changing research in screening, immunotherapy, targeted agents, chimeric antigen receptor (CAR) T-cell therapy, and more.
Key opinion leaders spoke with OncLive
ahead of the conference to share the top abstracts they believe could have the greatest impact on clinical practice and patient outcomes across lymphomas, gastrointestinal cancers, genitourinary cancers, and lung cancer.
Anas Younes, MD, PhD, medical oncologist, chief, Lymphoma Service, Memorial Sloan Kettering Cancer CenterActivity and tolerability of the first-in-class anti-CD47 antibody Hu5F9-G4 with rituximab (Rituxan) tolerated in relapsed/refractory non-Hodgkin lymphoma (NHL): Initial phase Ib/II results (Abstract 7504)
Anas Younes, MD, PhD
In a 3+3 dose-escalation design, heavily pretreated patients with diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) were treated with Hu5F9-G4, a first-in-class humanized CD47-targeted antibody and maintenance rituximab (NCT02953509). The combination was found to be well tolerated and the maximum-tolerated dose of Hu5F9-G4 was not reached up to 30 mg/kg weekly in the phase Ib portion.
Results with the recommended phase II dose showed that the overall response rate (ORR) was 50%, and the complete response (CR) rate was 32%. As of the data cutoff in January 2018, 90% of patients who responded continued to be in response. Phase II cohorts are ongoing for patients with indolent lymphoma and DLBCL.
“This is a small study but provides promising data on the potential therapeutic value of CD47-targeted therapy. Recently, the FDA granted Hu5F9-G4 fast track designation for relapsed DLBCL and FL.”Updated safety and long-term clinical outcomes in TRANSCEND NHL 001, pivotal trial of lisocabtagene maraleucel (liso-cel; JCAR017) in relapsed/refractory aggressive NHL (Abstract 7505)
Phase I results of this study previously showed that treatment with the CAR T-cell product JCAR017 demonstrated a CR rate of 59% and an ORR of 86% for patients with relapsed/refractory DLBCL (NCT02631044). In the findings to be presented at this meeting, researchers reported data from all patients in the DLBCL cohort, the FULL cohort, which includes DLBCL NOS (de novo or transformed from FL); primary mediastinal B-cell lymphoma; and follicular lymphoma grade 3B treated with liso-cel at various doses. Data from a CORE cohort comprises patients meeting inclusion criteria for the pivotal cohort, including those with DLBCL NOS and high-grade lymphoma.
Results showed that the best ORR in the FULL and CORE cohorts was 74% and 80%, respectively, and the best CR was 52% in FULL and 55% in CORE. There was an increase in durability of response at the second dose level (DL2; 108 CAR T cells) in the CORE population; the 6-month ORR and CR rate was 50% and 50% with DL2 versus 40% and 30% at dose level 1. Long-term efficacy will be reported at the meeting, as well.
Among 91 patients across the study evaluable for safety, 35% of patients had cytokine release syndrome (CRS); however only 1 patients had grade 3/4 CRS. Nineteen percent of patients had neurotoxicty of any grade, with 12% having grade 3/4. However, at the data cutoff all except one event had been resolved.
"This study demonstrates that the safety profile of different CD19 CAR T-cell therapies may vary among different products. In this case, the incidence of grade 3/4 cytokine release syndrome and neurotoxicity seems to be lower than what has been previously reported with other products. If confirmed, outpatient CAR T-cell therapy may become reality for selected patients."RELEVANCE: Phase III randomized study of lenalidomide (Revlimid) plus rituximab (R2) versus chemotherapy plus rituximab, followed by rituximab maintenance, in patients with previously untreated follicular lymphoma (Abstract 7500)
Following promising phase II data with lenalidomide and rituximab, the global phase III RELEVANCE trial examined R2
compared with rituximab plus chemotherapy followed by rituximab in previously untreated grade 1 to 3A patients with follicular lymphoma (NCT01650701). Findings showed that neither coprimary endpoint of progression-free survival (PFS) or CR/unconfirmed CR favored R2
; the efficacy was similar in both arms. However, the safety data differed; grade 3/4 laboratory abnormalities and febrile neutropenia were higher with rituximab/chemotherapy at 34% versus 50%, and 2% versus 6%, respectively. Meanwhile, there were higher grade 3/4 cutaneous events with R2
at 7% vs 1%.