Background: In the LOTIS-2 study, patients (pts) with relapsed/refractory (R/R) DLBCL treated with loncastuximab-tesirine (lonca), a CD19 directed antibody-drug conjugate, demonstrated an overall response rate (ORR) and complete response rate (CRR) of 48.3 % and 24.1%. However, there is a paucity of data evaluating outcomes with lonca in the real-world setting (RWS). Hence, we performed a multicenter retrospective study to describe pt characteristics and clinical outcomes in R/R DLBCL pts receiving lonca in this setting.

Methods: This retrospective study included pts with R/R DLBCL treated with commercial lonca at 21 academic centers in USA. Clinicopathologic data, treatment outcomes and adverse event (AE) data were collected. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier method and characteristics associated with survival and CR calculated using Cox proportional hazards model and logistic regression. Response was assessed per institutional standards.

Results: 187 pts were analyzed with a median follow-up of 12.5 months (mo). Median age was 68 years (range 22-95), 64% male, and 85% white ( Table 1). Most common histology was DLBCL (55% de novo, 22% transformed from low-grade) and 19% were double hit (DH). Thirty-two percent (n=59) had primary refractory disease, 17% (n=31) prior autologous transplant, and 60% (n=112) prior CAR T-cell therapy (CART). Median number of treatment lines before lonca was 4 (1-11) with 81% (n=151) receiving lonca in 4 th line (4L) or later and 8 pts treated off-label in 2 nd line. More pts receiving lonca in ≥4L had prior CART (72% vs 8%, p <0.001). CD19 status was confirmed prior to lonca in 128 pts (68%) with 109 (58%) confirmed CD19+.

The ORR/CRR were 33% and 14%, respectively. Median PFS was 2.1 mo (95%CI=1.8-2.6) and median OS 4.6 mo (95%CI=3.7-5.8). 12-month PFS and OS were 12% and 20%. The CRR in 2L/3L, 4L, and >4L were 15%, 13%, and 15% with ORR of 44%, 26%, and 33%, respectively. Figure 1 shows PFS stratified by response with median PFS not reached in those achieving CR. Patients with a CR to last therapy prior to lonca had superior median PFS (8.8 vs 2.0 mo, p<0.01) and OS (10.8 vs 4.5 mo, p =0.01). Factors associated with achieving CR to lonca included CR to last prior therapy (OR 8.3, p<0.01) and nonGCB subtype (OR 3.9, p=0.02). No pts with bulky disease (>10 cm) had objective response. In multivariable analysis (MVA) including factors in Table 1, elevated LDH (HR 1.8, p=0.02; 95%CI=1.1-2.9) and bulky disease (HR 1.7, p=0.03; 95%CI=1.1-2.6) were associated with inferior PFS while CR to last therapy was associated with superior PFS (HR 0.2, p=0.02; 95%CI=0.05-0.76). Bulky disease (HR 2.3, p<0.01; 95%CI=1.4-3.5), HGBL histology (HR 6.1, p<0.01; 95%CI=2.6-14.5), and elevated LDH (HR 2.0, p<0.01; 95%CI=1.2-3.3) were associated with inferior OS, while CR to last therapy (HR 0.4, p=0.05; 95%CI=0.13-0.98) was associated with superior OS in MVA.

Neither CD19 status nor prior CART were associated with PFS, OS, or CR. In pts receiving lonca after CART, ORR/CRR were 31% and 15%, respectively, and median PFS/OS were 2.0mo (95%CI=1.6-2.7) and 4.6mo (95%CI=3.2-6.1). In pts who received tafasitamab (n=15) and CART (n=7) after lonca, CR was 13% and 29%, respectively.

The most commonly documented AE was cytopenias (45%), followed by peripheral edema, and rash (27% and 27% respectively). Infection was seen in 5% and AEs led to lonca discontinuation in 14%, including peripheral edema (24%) and rash (28%).

Conclusions: In this heavily pre-treated population enriched with prior CART exposure, HGBL, and DHL, ORR and CRR to lonca were lower than previously reported. Nonetheless, we found that pts who achieve a CR to lonca have favorable outcomes and factors associated with achieving a CR include lack of bulky disease, nonGCB subtype, and achieving a CR to most recent therapy prior to lonca. Receipt of prior CART did not negatively impact outcomes to lonca. Furthermore, responses were seen with CD19-directed therapies following lonca failure, suggesting sequencing of CD19 therapy pre and post lonca was successful.

Ayers:ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees. Sawalha:Beigene: Research Funding; TG Therapeutics: Research Funding; Celgene/BMS: Research Funding. Dong:EUSA Pharma, a Recordati Group company.: Research Funding; Robert A. Winn Diversity in Clinical Trials Career Development Award, funded by Gilead Sciences: Research Funding. Baird:Kite Pharma-Gilead: Research Funding, Speakers Bureau; Genentech-Roche: Research Funding; Regeneron Pharmaceuticals: Research Funding; Cellular Biomedicine Group: Research Funding. Huntington:Janssen Pharmaceuticals: Consultancy; Genentech: Consultancy; Epizyme, Inc.: Consultancy; Seagen Inc.: Consultancy; Pharmacyclics LLC, An AbbVie Company: Consultancy; Lilly USA, LLC: Consultancy; Merck: Consultancy; TG Therapeutics: Consultancy; Arvinas: Consultancy; Novartis: Consultancy; AstraZeneca: Consultancy; Bayer Healthcare: Consultancy; BeiGene USA, Inc.: Consultancy; Servier Pharmaceuticals LLC: Consultancy; Tyme Inc: Consultancy; ADC Therapeutics: Consultancy; AbbVie: Consultancy. Narkhede:Genentech-Roche: Honoraria, Research Funding, Speakers Bureau; Kite: Honoraria, Research Funding; ADC Therapeutics: Honoraria, Research Funding; AbbVie: Honoraria; Gilead: Research Funding; TG Therapeutics: Research Funding; BeiGene: Research Funding; EUSA: Research Funding; Adaptive: Research Funding. Frosch:Seagen: Membership on an entity's Board of Directors or advisory committees; Abbvie: Research Funding; Roche: Research Funding; AstraZenica: Research Funding. Smith:BeiGene: Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics, AstraZeneca, Ayala (spouse), Bayer, BeiGene, Bristol Myers Squibb (spouse), De Novo Biopharma, Enterome, Genentech, Inc., Ignyta (spouse), Incyte Corporation, Kymera Therapeutics, Merck Sharp and Dohme Corp., MorphoSys, Nanjing Pharmaceu: Research Funding; ADC Therapeutics, AstraZeneca, BeiGene, Epizyme, Karyopharm, KITE pharma, Incyte, Numab Therapeutics AG, Abbvie, Coherus Biosciences, advisory board (spouse) Genentech, Inc.: Consultancy. Winter:BeiGene: Consultancy; AstraZeneca: Consultancy; Seattle Genetics: Consultancy; Janssen: Consultancy; ADC Therapeutics: Consultancy. Landsburg:Epizyme: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Travel funding; Curis: Research Funding; Calithera: Membership on an entity's Board of Directors or advisory committees, Research Funding; ADCT: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Morphosys: Membership on an entity's Board of Directors or advisory committees. Hamadani:Takeda: Research Funding; Genentech: Honoraria; Myeloid Therapeutics: Honoraria; Spectrum Pharmaceuticals: Research Funding; Astellas: Research Funding; Bristol Myers Squibb: Consultancy; Astra Zeneca: Speakers Bureau; Novartis: Consultancy; SeaGen: Consultancy; MorphoSys: Consultancy; Legend Biotech: Consultancy; Kadmon: Consultancy; Incyte: Consultancy; Genmab: Consultancy; Gamida Cell: Consultancy; BeiGene: Speakers Bureau; Kite, a Gilead Company: Consultancy, Speakers Bureau; AstraZeneca: Speakers Bureau; Caribou: Consultancy; Genmab: Consultancy; BeiGene: Speakers Bureau; Sanofi Genzyme: Speakers Bureau; ADC therapeutics: Consultancy, Honoraria, Research Funding, Speakers Bureau; CRISPR: Consultancy; Abbvie: Consultancy; Omeros: Consultancy. Romancik:Astra Zeneca: Consultancy; KITE: Consultancy. Advani:Epizyme: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees; Regeneron: Research Funding; Beigene: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; ADCT: Membership on an entity's Board of Directors or advisory committees, Research Funding; Cyteir: Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees; Merck: Research Funding; Gilead: Research Funding; Seagen: Research Funding. Johnson:Seagen: Consultancy; AstraZeneca: Consultancy, Research Funding; Abbvie: Consultancy; Medically Home: Research Funding; ADC Therapeutics: Consultancy; Incyte: Consultancy, Research Funding. Grover:ADC Therapeutics: Consultancy, Honoraria; Sangamo: Current holder of stock options in a privately-held company; Novartis: Honoraria; Tessa Therapeutics: Research Funding; Caribou Biosciences: Honoraria; Seagen: Honoraria; Genentech: Honoraria; Kite: Honoraria; Seattle Genetics: Consultancy. Crombie:ADC therapeutics: Consultancy; Genmab: Consultancy; Roche: Research Funding; Merck: Research Funding; Abbvie: Research Funding; Bayer: Research Funding; Karyopharm: Consultancy; Incyte: Consultancy; Kite: Consultancy; Seagen: Consultancy. Nastoupil:Gilead Sciences/Kite Pharma: Honoraria, Research Funding; Regeneron: Honoraria; Genentech, Inc., Genmab, Gilead/Kite, Janssen, Merck, Novartis, Takeda: Honoraria, Research Funding; Daiichi Sankyo: Honoraria, Research Funding; DeNovo: Honoraria; AstraZeneca: Honoraria; Caribou Biosciences: Honoraria, Research Funding; Bristol Myers Squibb/Celgene: Honoraria, Research Funding; ADC Therapeutics: Honoraria; AbbVie: Honoraria. Epperla:ADC Therapeutics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Lilly: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Speakers Bureau; Beigene: Research Funding, Speakers Bureau.

Figure 1
Figure 1
View largeDownload slide
This content is only available as a PDF.
2023
Sign in via your Institution