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442 Polatuzumab Vedotin Combined with R-ICE (PolaR-ICE) As Second-Line Therapy in Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Program: Oral and Poster Abstracts
Type: Oral
Session: 626. Aggressive Lymphomas: Prospective Therapeutic Trials: Immune Based and Targeted Therapies in Relapsed/Refractory Large B-Cell Lymphoma
Hematology Disease Topics & Pathways:
Research, clinical trials, Biological therapies, Antibody Therapy, Lymphomas, non-Hodgkin lymphoma, Clinical Research, B Cell lymphoma, Combination therapy, Diseases, aggressive lymphoma, Therapies, Lymphoid Malignancies
Sunday, December 11, 2022: 10:15 AM

Alex F. Herrera, MD1, Lu Chen, PhD2*, Jennifer L. Crombie, MD3*, Jonathon B. Cohen, MD, MS4, Ranjana H. Advani, MD5, Ann S. LaCasce, MD6, Leslie L. Popplewell, MD, FACP, MPH7, Sandrine Puverel, PhD1*, Lacolle Peters8*, Shari Daniels1*, James Godfrey, MD9, Geoffrey Shouse, PhD, DO10, Matthew Mei, MD11, Swetha Kambhampati, MD12, Elizabeth L. Budde, MD, PhD13, Liana Nikolaenko, MD11, Steven T. Rosen, MD14, Larry W. Kwak, MD, PhD15, Stephen J Forman, MD10 and Matthew J. Matasar, MD, MS16

1City of Hope, Duarte, CA
2Department of Information Sciences, City of Hope, Duarte
3Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
4Department of Hematology and Medical Oncology, Emory University, Atlanta, GA
5Department of Medicine, Division of Oncology, Stanford University, Stanford, CA
6Division of Hematologic Malignancies, Dana-Farber Cancer Inst., Boston, MA
7Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA
8City of Hope National Medical Center, Duarte, CA
9City of Hope Comprehensive Cancer Center, Duarte, CA
10Department of Hematology/HCT, City of Hope National Medical Center, Duarte, CA
11Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA
12City of Hope National Medical Center, DUARTE, CA
13Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA
14Department of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA
15Deputy Director, City of Hope Comprehensive Cancer Center, Duarte, CA
16215 West 90th St, 14E, Memorial Sloan Kettering Cancer Center, New York, NY

Introduction: Currently, the standard of care for patients (pts) with relapsed/refractory (RR) diffuse large B-cell lymphoma (DLBCL) who relapse > 1 year after frontline treatment is salvage chemoimmunotherapy followed by autologous stem cell transplantation (ASCT) in appropriately selected, chemosensitive pts. Following first-line therapy (tx) with a rituximab-containing anthracycline-based regimen in the modern era, response rates to platinum-based chemoimmunotherapy are suboptimal. More effective salvage regimens for RR DLBCL remain an unmet need. Polatuzumab vedotin (Pola) is an antibody-drug conjugate directed against CD79b that is safe and effective when combined with chemotherapy in frontline and relapsed, transplant-ineligible DLBCL pts [Tilly NEJM 2022, Sehn, JCO 2020]. We evaluated the safety and efficacy of Pola combined with rituximab, ifosfamide, carboplatin, and etoposide (RICE) as second-line tx in RR DLBCL in a multicenter phase 2 study.

Methods: Adult transplant-eligible pts with ECOG ≤ 2 who had biopsy-proven RR DLBCL following frontline CD20-directed anthracycline-based chemoimmunotherapy were eligible. Pts with DLBCL not otherwise specified (NOS), transformed indolent lymphoma, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma (HGBCL) NOS, and HGBCL with MYC and BCL2 rearrangements were eligible. Pts with central nervous system lymphoma, peripheral neuropathy (PN) ≥ grade (gr) 2 or prior tx of RR DLBCL were excluded. Participants received PolaR-ICE: 1.8mg/kg Pola day (d) 1, rituximab 375mg/m2 d1, etoposide 100 mg/m2 IV d1-3, carboplatin AUC 5 (750 mg max) IV d2, ifosfamide IV 5000 mg/m2 d2 (inpatient) or divided between d1-3 (outpatient) every 21d for 2 cycles followed by PET-CT. G-CSF prophylaxis was mandatory. Pts in CR were eligible to proceed directly to ASCT or could receive a 3rd cycle of PolaR-ICE at investigator’s discretion. Pts with partial response (PR) [or stable disease, MD discretion] received a 3rd cycle of PolaR-ICE. After ASCT, pts in ongoing response who had recovered from ASCT toxicities were eligible to receive Pola consolidation (1.8mg/kg) in 21d cycles starting d+30-60 to complete a cumulative 6 doses of Pola. A safety lead-in of up to 8 pts were enrolled according to the IQ rolling 6 design, with a de-escalation dose available (Pola 1.4mg/kg). Following the lead-in, a 2-stage design was employed with 20 pts enrolled (including lead-in) and since 8+ CRs were observed, the study proceeded to enroll a total of 40 pts. The co-primary endpoints were safety and CR rate according to 2014 Lugano classification. ORR, PFS and overall survival were secondary endpoints.

Results: 41 pts were enrolled; baseline characteristics are shown in Table 1. 37 pts were evaluable for response: 1 pt died prior to response assessment, 1 pt was inevaluable for response and replaced, 1 pt had clinical progressive disease (PD) and counted in ORR evaluation as PD, and 1 pt is pending response evaluation. 40 pts have toxicity data available, including 22 pts who received 3 cycles of PolaR-ICE, 16 treated with 2 cycles to date, and 2 pts who received 1 cycle to date. Of 38 pts (37 evaluable + 1 clinical PD), 35 had an objective response after 2 cycles of PolaR-ICE for an ORR of 92%, 21 (55%) had a CR, 14 (37%) had a PR, 1 had stable disease and 2 had PD. The end of salvage (PolaR-ICE x 2 or 3) ORR was 89% and CR rate 61% (1 PR became PD and 2 PR converted to CR with a 3rd cycle). To date, 21 pts proceeded to ASCT and 13 pts received consolidation Pola. The most common treatment-emergent adverse events (TEAE, all gr) related to PolaR-ICE were anemia (78%), nausea (70%), thrombocytopenia (70%), leukopenia (50%), fatigue (48%), neutropenia (48%), lymphopenia (38%), constipation (35%), hypertension (30%), and hypophosphatemia (28%). The most common gr ≥ 3 TEAEs were anemia (43%), thrombocytopenia (43%), neutropenia (43%), and no other non-hematologic TEAE occurred in more than 2 (5%) pts. 1 pt underwent Pola dose reduction due to gr 4 cytopenias, gr 2 nausea. Gr ≥ 3 infection/febrile neutropenia/sepsis occurred in 3 (8%) pts. 1 pt had a study treatment-related gr 5 AE due to sepsis. PN occurred in 10 (25%) pts, all gr 1 except one gr 2 event.

Conclusion: PolaR-ICE produced a high ORR with CR in a majority of pts and the safety profile was similar to RICE, without added toxicity due to Pola. Longer follow-up is needed to assess the durability of responses and outcomes following ASCT/Pola consolidation.

Disclosures: Herrera: KiTE Pharma: Research Funding; ADC Therapeutics: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Takeda: Consultancy; Tubulis: Consultancy; Adicet Bio: Consultancy; Regeneron: Consultancy; Genmab: Consultancy; Pfizer: Consultancy; Caribou: Consultancy; Genentech: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Gilead: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Karyopharm: Consultancy. Crombie: Kite: Consultancy; Roche: Research Funding; Bayer: Research Funding; Merck: Research Funding; Abbvie: Research Funding; Karyopharm: Consultancy; Incyte: Consultancy. Cohen: Aptitude Health: Consultancy; Janssen: Consultancy; Novartis: Research Funding; Kite Pharma/Gilead: Consultancy; Lilly Oncology/Eli Lilly: Consultancy, Research Funding; Takeda: Research Funding; Astrazeneca: Consultancy, Research Funding; HutchMed: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Genentech: Research Funding; BMS/Celgene: Research Funding. Advani: ADC Therapeutics, Cyteir, Daiichi Sankyo, Gilead, Merck, Regeneron, Roche, Seattle Genetics: Research Funding; ADC Therapeutics, BMS, Daiichi Sankyo, Epizyme, Gilead, Incyte, Merck, Roche, Sanofi: Consultancy. LaCasce: Research to Practice: Consultancy; Seattle Genetics: Consultancy. Godfrey: Secura Bio: Research Funding; Merck: Research Funding. Shouse: Kite Pharma: Speakers Bureau; Beigene Inc USA: Honoraria. Mei: Incyte/Morphosys: Research Funding, Speakers Bureau; Novartis: Honoraria; CTI: Honoraria; BMS: Research Funding; Beigene: Research Funding; EUSA: Honoraria. Budde: Mustang Therapeutics: Research Funding; AstraZeneca: Research Funding; Amgen: Research Funding; Amgen: Research Funding; Merck: Research Funding; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Ziopharm: Other: DMSC member for a phase 1 clinical; BeiGene: Membership on an entity's Board of Directors or advisory committees. Rosen: Pheromone Bio, Inc: Consultancy; Exicure: Consultancy; Apobiologix/Apotex Inc: Consultancy; PharmaGene, LLC: Consultancy; Trillium Therapeutics, Inc: Consultancy; Verastem, Inc: Consultancy; NeoGenomics: Membership on an entity's Board of Directors or advisory committees; Pepromene Bio, Inc: Membership on an entity's Board of Directors or advisory committees; Pepromene Bio, Inc: Current holder of stock options in a privately-held company; Exicure: Current holder of stock options in a privately-held company; January Biotech: Current holder of stock options in a privately-held company; Trillium Therapeutics: Current holder of stock options in a privately-held company. Matasar: ADC Therapeutics: Consultancy, Honoraria; Juno Therapeutics: Consultancy; F. Hoffmann-La Roche Ltd.: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Consultancy; ImmunoVaccine Technologies: Honoraria, Research Funding; GlaxoSmithKline: Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Rocket Medical: Consultancy, Research Funding; Merck: Consultancy, Current equity holder in private company; AstraZeneca: Consultancy; TG Therapeutics: Consultancy; IMV Therapeutics: Consultancy, Honoraria; Epizyme: Consultancy, Honoraria; Pharmacyclics: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Bayer: Consultancy, Honoraria, Research Funding; Genentech, Inc.: Consultancy, Honoraria, Research Funding; Teva: Consultancy; IGM Biosciences: Research Funding; Karyopharm: Consultancy.

OffLabel Disclosure: Polatuzumab vedotin is approved after 2 prior therapies in the US, is approved as frontline therapy for DLBCL in Europe.

*signifies non-member of ASH