Real-World Outcomes in Relapsed/Refractory DLBCL Patients Who Received Polatuzumab Vedotin PLUS Bendamustine and Rituximab or Tafasitamab Plus Lenalidomide By Line of Therapy

BACKGROUND: Polatuzumab vedotin (Pola) combined with bendamustine and rituximab (BR) and tafasitamab (Tafa) combined with lenalidomide (Len) are approved for patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). Notably, Pola and Tafa trials included a significant proportion of second-line patients (49% in L-MIND and 27% in the GO29365 trial). The efficacy of these treatments in more heavily pretreated patients in the real world remains uncertain. The objective of this study was to examine the effectiveness of Pola-BR and Tafa-Len by line of therapy.

METHODS: Adult patients diagnosed with DLBCL between January 1, 2014 and March 31, 2022 who were treated with either Pola or Tafa were retrospectively identified from COTA EMR data. COTA represents over 200 sites of care (50% academic/50% community) in the United States. Outcomes were analyzed for patients who received Pola-BR or Tafa-Len, with the initiation of respective treatment assigned as the index date. Patient characteristics, complete response rate (among those with a documented response), progression-free survival (PFS) and overall survival (OS) were reported by line of therapy (2L vs 3L+). Overall survival (OS) was defined as the time from index date to death, and PFS as the time from index date to disease progression, next line of therapy not due to adverse event or death. Descriptive analyses included means, medians, and standard deviations (SD) for continuous variables, and frequencies and proportions for categorical variables. Median PFS and OS were estimated using Kaplan-Meier curves and unadjusted hazard ratios (HR) were estimated using Cox proportional hazard model with 95% confidence interval (CI) reported.

RESULTS: Among 3960 DLBCL patients identified from COTA, 96 patients were treated with Pola-containing therapy, and 30 patients were treated with Tafa-containing therapy.

Analysis was limited to patients receiving Pola-BR (N=60). Patients receiving Pola-B or Pola-R (N=21), Pola-monotherapy (N=14), or Pola in combination with other therapies were excluded. Pola-BR patients were on average 69 years old, 58% male, and 13% had high-grade lymphoma. Over 70% (N=43) of patients received Pola-BR in the 3L+ setting (vs 28% in 2L). Within a median follow-up of 15 months (2L: 9.8 mo, 3L+: 21 mo), the median treatment duration of Pola-BR was 2.4 months (2L: 1.5 mo, 3L+: 2.6 mo), a complete response was observed in 27% of patients (2L: 40%, 3L+: 22%). Median PFS was 4.6 months (2L: 5.5 mo, 3L: 4.6 mo; unadjusted HR of 3L+ vs. 2L: 0.75, 95% CI: 0.39-1.4) and median OS was 7.3 months (2L: 7.1 mo, 3L+: 7.3 mo; unadjusted HR of 3L+ vs. 2L: 1.3, 95% CI: 0.58-3.0). There were 9 patients (15%) who subsequently underwent CD19-directed CAR T-cell therapy. Upon censoring at CAR-T initiation, OS was 7.3 months. (2L: 7.1 mo, 3L+: 7.3 mo). (Table 1).

Twenty-five patients received Tafa-Len. Tafa-Len patients were on average 72 years old, 52% male, and 12% had high-grade lymphoma. Over 75% of patients received Tafa-Len in the 3L+ setting (vs 24% in 2L). Within a median follow-up of 12 months (2L: 5.4 mo, 3L+: 12 mo), the median treatment duration was 1.7 months (2L: 3.3 mo, 3L: 1.6 mo), a complete response was observed in 8.7% of patients (2L: 20%, 3L+: 5.6%). A shorter median PFS was observed in 3L+ than in 2L (2L: Not reached, 3L+: 2.0 mo; unadjusted HR of 3L+ vs. 2L: 9.0, 95% CI: 1.2-68). Median OS was 6.6 months (2L: 6.3 mo, 3L+: 6.2 mo; unadjusted HR of 3L+ vs. 2L: 3.3, 95% CI: 0.42-26). No patients received CAR T-cell therapy in a subsequent line of therapy. Hence, OS remained unchanged after censoring at CAR-T initiation. (Table 2).

CONCLUSIONS: This real world analysis examined the outcomes of Pola-BR and Tafa-Len in patients with R/R DLBCL treated in 2L and 3L+ separately and suggested a trend of lower CR rates and PFS in 3L+ relative to 2L, particularly for the Tafa-Len combination. The study was limited by small sample size and short follow up. Future study is needed to confirm the findings with larger samples and a longer follow-up.

Hamadani:Legend Biotech: Consultancy; Sanofi Genzyme: Speakers Bureau; Genmab: Consultancy; SeaGen: Consultancy; Gamida Cell: Consultancy; Novartis: Consultancy; AstraZeneca: Speakers Bureau; Astellas Pharma: Research Funding; Spectrum Pharmaceuticals: Research Funding; Takeda: Research Funding; Abbvie: Consultancy; Omeros: Consultancy; ADC Therapeutics: Consultancy, Research Funding, Speakers Bureau; Kadmon: Consultancy; Kite: Consultancy; MorphoSys: Consultancy; Incyte Corporation: Consultancy; Medical University of Wisconsin: Current Employment; BioGene: Speakers Bureau. Liao:ADC Therapeutics: Current Employment, Current equity holder in private company, Current holder of stock options in a privately-held company. Wilson:ADC Therapeutics: Consultancy; Genesis Research: Current Employment. Howarth:ADC Therapeutics: Consultancy; Genesis Research: Current Employment. Flores:Genesis Research: Current Employment; ADC Therapeutics: Consultancy. Chen:ADC Therapeutics: Current Employment, Current equity holder in private company, Current holder of stock options in a privately-held company.