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1620 Canadian Cancer Trials Group (CCTG) LY.17: A Randomized Phase II Study Evaluating Novel Salvage Therapy Pre-Autologous Stem Cell Transplant (ASCT) in Relapsed/Refractory Diffuse Large B-Cell Lymphoma (RR-DLBCL) - Outcome of Rituximab-Dose-Intensive Cyclophosphamide, Etoposide, Cisplatin (R-DICEP) Versus R-GDP

Program: Oral and Poster Abstracts
Session: 626. Aggressive Lymphomas: Prospective Therapeutic Trials: Poster I
Hematology Disease Topics & Pathways:
Research, clinical trials, Lymphomas, Non-Biological therapies, Clinical Research, B Cell lymphoma, Chemotherapy, Diseases, aggressive lymphoma, Therapies, Lymphoid Malignancies
Saturday, December 10, 2022, 5:30 PM-7:30 PM

Douglas A. Stewart, MD1, Lois E. Shepherd2, Jill J. Dudebout, MD3*, Jean-François Larouche, MD4, Neil Chua, MD5*, Tara Baetz, MD6*, Michael Crump7, Mona Shafey, MD8, Nizar Abdel-Samad, MD9, Sue Robinson, MD10*, Isabelle Fleury, MD11, Deborah Marcellus, MD12*, Pamela Skrabek, MD, FRCPC13, Jesse Kelly14*, Annette E. Hay15, Bingshu Chen16* and John Kuruvilla, MD17

1Tom Baker Cancer Centre, Calgary, AB, Canada
2Canadian Cancer Trials Group, Queen's University, Kingston, ON, Canada
3Queens University, Kingston, ON, CAN
4Hôpital Enfant-Jésus, Centre Hospitalier Universitaire de Quebec, Quebec City, QC, Canada
5Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada
6Queen's University, Kingston, ON, Canada
7Princess Margaret Hospital, Toronto, ON, Canada
8Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada
9The Moncton Hospital, Moncton, NB, Canada
10Queen Elizabeth II Health Science Center, Halifax, NS, Canada
11Maisonneuve-Rosemont Hospital, Institute of Hematology, Oncology and Cell Therapy, Montreal University, Montreal, QC, Canada
12Hamilton Regional Cancer Center, Hamilton, ON, CAN
13Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada
14Canadian Cancer Trials Group, Kingston, ON, Canada
15Canadian Cancer Trials Group, Cancer Research Institute, Kingston, ON, Canada
16Queen's University, Kingston, ON, CAN
17University Health Network, Princess Margaret Cancer Center, Toronto, ON, Canada

Introduction: The CCTG LY.12 trial established rituximab combined with gemcitabine, dexamethasone and cisplatin (R‐GDP) as a standard salvage chemotherapy option prior to ASCT for patients (pts) with relapsed/refractory (RR) DLBCL (Crump JCO 2014). CCTG LY.17 is an ongoing multi‐arm randomized phase II “pick a winner” trial evaluating novel salvage therapy compared with R‐GDP in ASCT-eligible RR‐DLBCL pts.

Methods: The primary endpoint of the study is overall response rate (ORR) using CT imaging. According to the protocol futility rule, any treatment arm with an ORR lower than the R-GDP control arm at the first interim analysis (n = 16), or less than 10% higher at the second interim analysis (n=32) would not continue to full target accrual of 64 pts per treatment arm. Encouraging results could then be pursued in a larger phase III trial designed to detect differences in progression-free survival (PFS). This report involves the component of the trial that randomly allocated pts to either 1 cycle of inpatient R-DICEP (Rituximab 375mg/m2 IV or 1400mg sc days 1 and 5 plus dose-intensive Cyclophosphamide 5.25g/m2, Etoposide 1050mg/m2, Cisplatin 105mg/m2 divided over days 2-4, with daily filgrastim starting day 15 until apheresis of blood stem cells approximately between days 20-22) or to 3 cycles of outpatient R-GDP. This report is the result of the protocol-specified second interim analysis.

Results: A total of 67 pts were randomized to R-DICEP (n=32) or to R-GDP (n=35) between April 2016 and April 2021. Table 1 lists baseline pt characteristics. Four pts (R-DICEP=2, R-GDP=2) were not evaluable for response. The ORR was 65.6% for R-DICEP (70.0% for evaluable pts), which was 17% greater than the ORR of 48.6% for R-GDP (51.5% for evaluable pts). Additionally, only 1 (3.1%) R-DICEP pts versus (vs) 11 (31.4%) R-GDP pts experienced progressive disease as best response to salvage therapy. Of interest, the ORR to salvage was 40% (14/35) for pts primary refractory to RCHOP (no response to RCHOP or progressive disease during or <3mo post RCHOP) vs 75% (24/32) for those who relapsed >3mo post RCHOP (p=0.006), with ORR to R-DICEP of 50% vs 81.3% and ORR to R-GDP of 31.6% vs 68.8% for primary refractory vs relapse >3mo, respectively. The ORR based on PET-CT scan was 50.0% vs 31.4% for the R-DICEP (n=26) vs R-GDP (n=25) arms, respectively. Overall, 23 (71.9%) R-DICEP pts and 19 (54.3%) R-GDP pts underwent ASCT. In total, 26 out of 27 (96.3%) R-DICEP, and 18 out of 20 (90%) R-GDP pts underwent successful autologous blood stem cell collection (requiring >1 attempt in 0 R-DICEP and 2 R-GDP pts). The median time to neutrophil engraftment post-ASCT was 13 (1-32) and 12 (1-22) days, and to platelet engraftment was 12 (1-50) and 16 (7-22) days for R-DICEP and R-GDP pts, respectively. Regarding adverse events (AEs) of salvage therapy and subsequent ASCT, R-DICEP pts had higher rates of culture positive infection (84% vs 40%), platelet (96.6% vs 60.0%) and red cell (75.0% vs 42.9%) transfusions, diarrhea (44% vs 14%), serious adverse events (50% vs 34.3%), and treatment-related mortality (3.1% vs 0%) but similar rates of other AEs including arrhythmia (6% vs 9%), bleeding (0 vs 0), fungal infections (0 vs 0) and pneumonitis (0 vs 0). At a median duration of follow-up of 26.9 months (R-DICEP 26.4 months and R-GDP 27.4 months), the 1-year PFS rate was 42% for R-DICEP and 32% for R-GDP (HR 0.59, 95%CI: 0.32-1.09, logrank p=0.09), and 1-year OS rate was 65% for R-DICEP and 55% for R-GDP (HR 0.675, 95%CI: 0.333-1.369, logrank p=0.27).

Conclusions: Although the 17% improvement in ORR for R-DICEP vs R-GDP in the second interim analysis exceeded the pre-specified 10% threshold required proceed to full accrual of 64 pts in the R-DICEP arm, we decided to stop accrual to the R-DICEP arm of the LY.17 trial due to slow accrual, higher AE rates, and greater utilization of healthcare resources including hospitalization needed to administer treatment, which limits feasibility of R-DICEP at several Canadian centres. The LY.17 trial continues testing other salvage regimens.

Disclosures: Stewart: Seagen: Honoraria; Roche: Honoraria; Janssen: Honoraria; Beigene: Honoraria; Novartis: Honoraria; Gilead: Honoraria; Apobiologix: Honoraria. Chua: Seagen: Honoraria; Abbvie: Honoraria; Incyte: Honoraria; Amgen: Honoraria; Merck: Honoraria; Gilead: Honoraria; Bayer: Honoraria; Pfizer: Honoraria. Baetz: Servier: Honoraria; Roche: Honoraria; Gilead: Honoraria; Astrazeneca: Honoraria; BeiGene: Honoraria. Crump: Kyte-Gilead, Novartis: Honoraria; Roche: Research Funding. Shafey: BeiGene: Honoraria; Janssen: Honoraria; Astrazeneca: Honoraria; Novartis: Honoraria; BMS: Honoraria; Kite/Gilead: Honoraria; Incyte: Honoraria. Robinson: Roche: Honoraria; Janssen: Honoraria; Astrazeneca: Honoraria; BeiGene: Honoraria; AbbVie: Honoraria; Novartis: Honoraria. Fleury: Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Kite-Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees, Research Funding; Seagen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Beigene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Incyte: Membership on an entity's Board of Directors or advisory committees, Other: Grant during the conduct of the study , Research Funding, Speakers Bureau. Hay: Merck: Research Funding; Seagen: Research Funding; Karyopharm: Research Funding; Roche: Research Funding; AbbVie: Research Funding. Kuruvilla: Gilead: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria, Other: DSMB; Merck: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria; Medison Ventures: Consultancy; Antengene: Consultancy; Novartis: Honoraria; Janssen: Honoraria; Amgen: Honoraria; Astra Zeneca: Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; Inctye: Honoraria; Seattle Genetics: Consultancy, Honoraria; Pfizer: Honoraria; Lymphoma Canada: Membership on an entity's Board of Directors or advisory committees.

*signifies non-member of ASH