Background
Publication of the L-MIND-study led to the approval of tafasitamab/lenalidomide (TL) for patients with relapsed oder refractory diffuse large B-cell lymphoma (r/r DLBCL), who were ineligible for autologous stem-cell transplantation (ASCT). The findings of the L-MIND-study showed an overall response rate (ORR) of 60%, complete response rate (CRR) of 43%, median progression free survival (PFS) of 12.1 months, and median overall survival (OS) of 33.5 months. To analyze the real-world characteristics of patients treated with TL, we performed a multicenter retrospective study with patients who were teated with TL since the implementation of the Expanded Access Program (EAP) from 03/2020 until 07/2023.
Methods
We retrospectively analyzed the outcomes, demographics, data on diagnosis, prior therapies, adverse events (AEs), and treatment after TL of 127 patients with r/r DLBCL treated with TL in Germany and Austria in 18 institutions. OS and PFS are displayed by Kaplan-Meier graphs. Relationships with multiple covariables were calculated by Cox regression. We performed subgroup analyses with prior anti-CD19 therapy, primary refractory disease vs. relapsed disease, IPI, number of prior therapies, treatment after TL, age, and sex. The study was approved by the local Research Ethics Committees.
Results
Overall, only 37% of our patients met the L-MIND study eligibility criteria; most frequent reasons for ineligibility were more than 3 prior lines of therapy (52%), prior therapy with anti-CD19/IMiDs (19% prior CAR T-cell therapy and Bispecific Antibodies, 7% prior IMiDs), High-Grade-BCL/Follicular Lymphoma Grade 3A/CNS involvement/primary refractory lymphomas/Primary-Mediastinal-BCL/B-ALL (23%), or patients who had lymphoma-specific-therapy within 14 days prior to day 1 dosing with TL (8%). Patient characteristics are stated in Table 1. ORR for the entire cohort (n=127) was 33.1%, CRR 11.8%. Median PFS was 4.7 months (95% CI 6.9 - 11.6), or even 2.9 months (95% CI 2.2 - 3.2) including all causes of death as progression, and median OS 8.9 months (95% CI 5.0 - 11.0) for the whole cohort; see Figure 1. Compared to refractory disease (n=55, 43%), relapsed disease (n=72, 57%) was associated with better ORR (43% vs. 20%, P=0.008). PFS and OS were worse in the primary refractory compared to the relapsed group (median PFS 1.7 vs. 5.3 months, HR 2.79, 95% CI 1.82-4.28, P<0.001; median OS 4.5 vs. 12.9 months, HR 2.72, 95% CI 1.53-4.33, P<0.001). 36% of the patients had a low IPI (0-2, low risk), 55% had a higher IPI (3-5, high risk) at primary diagnosis. ORR (40% vs. 30%) and OS (median OS 9.1 vs. 5.6 months HR 1.76, 95% CI 1.04-2.99) were higher in the lower risk group than in the higher risk group. Fewer prior lines of therapy (1-2 vs. ≥3) were associated with longer median PFS (median 3.3 vs. 1.9 months HR 1.13 per additional line, 95% CI 1.00-1.28, P=0.057) and longer median OS (median 12.5 vs. 5.2 months HR 1.18, 95% CI 1.01-1.37, P=0.039). Median time between the administration of the last prior therapy and TL were 6.4 months. No significant relationships were found for age, sex, and preceding CAR-T treatment. Prior CAR T-cell therapy (24 of 127 patients, post-CAR T-cohort) showed only small differences in ORR (37.5%), PFS (7.9 months with CAR T vs. 12 months without CAR T) or OS (9.2 months with CAR T vs. 12.4 months without CAR T); CRR was higher than in patients not treated with CAR T prior to TL (21% vs. 9.7%). 10 of the analyzed 127 patients received CAR T-cell therapy after TL. Within this subgroup, ORR was 50%. In 2 of these 10 patients TL was used as bridging therapy to CAR T; 1 of 2 patients reached a PR, the other one died before CAR T-cell therapy. The most common hematological AE was neutropenia (67%), the most common non-hematological AEs included infections (31%) and rash and itching (9%).
Conclusions
We show that the outcomes including ORR, PFS and OS in the real-world setting were lower than observed in the preceding phase II clinical trial (L-MIND). TL seems to be less feasible for patients that show high-risk features; comorbidities, age, dose reductions and the number of pretreatment lines may add to this. The data suggests that TL can still be used after CAR T-cell therapy or as a bridge to CAR T-cell therapy. Our findings on the frequency of observed AEs are consistent with the L-MIND-study.
Disclosures
Topp:Roche: Consultancy, Research Funding; Takeda: Research Funding; GenMab: Consultancy; AstraZeneca: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Other: Travel support, Research Funding; Regeneron Pharmaceuticals, Inc.: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; AbbVie: Consultancy; Janssen: Consultancy, Other: Travel support. Greil:Roche: Honoraria, Research Funding. Melchardt:Roche: Honoraria. Lenz:Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Morphosys: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Genmab: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Constellation: 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; Miltenyi: Consultancy, Membership on an entity's Board of Directors or advisory committees; PentixPharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sobi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Immagene: Consultancy; Genase: Consultancy; Hexal/Sandoz: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Lilly: Consultancy; University Hospital Munster: Current Employment; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; NanoString: Membership on an entity's Board of Directors or advisory committees; BeiGene: Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Kerkhoff:Roche,Sobi: Honoraria; BeiGene, BMS, pharma: Honoraria; AbbVie, Amgen, Zeneca: Honoraria; Takeda: Honoraria. Hess:Kite/Gilead: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; BMS: Consultancy; Incyte: Consultancy, Honoraria, Research Funding; Morphosys: Research Funding; Astra: Consultancy, Honoraria; Lilly: Consultancy, Honoraria; ADC Therapeutics: Consultancy, Honoraria; Miltenyi: Consultancy; Roche: Consultancy, Honoraria; Novartis: Consultancy. Age Kos:Pfizer: Other: Travel funds. Mayer:Amgen, Abbvie: Other: travel grants; Amgen, Novartis Roche: Honoraria. Herling:Mundipharma EDO, Janpix, Novartis, Roche: Research Funding; Abbvie, Beigene, Janssen, Stemline, Takeda: Consultancy. Vucinic:MSD: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Sobi: Honoraria, Other: Travel/Accommodations/Expenses; Amgen: Honoraria; AstraZeneca: Honoraria; Janssen: Honoraria; Gilead/Kite: Consultancy, Honoraria; BMS/Celgene: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses; Novartis: Consultancy, Honoraria; Abbvie: Honoraria. Illerhaus:Roche: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Gilead Sciences: Honoraria; GlaxoSmithKline: Other: Travel, accommodations and expenses; BMS: Other: Travel, accommodations and expenses. Viardot:F. Hoffmann-La Roche Ltd, Abbvie, Kite/Gilead, BMS: Honoraria; BMS: Research Funding; F. Hoffmann-La Roche Ltd, Abbvie, Kite/Gilead, BMS: Consultancy. Mueller:AstraZeneca, BMS, Gilead, Janssen, Miltenyi biomedicine, Novartis: Consultancy; Miltenyi, BMS, Novartis, Gilead, Janssen, Incyte, AstraZeneca, Abbvie, Sobi, Beigene: Honoraria; BMS, AstraZeneca, Gilead: Research Funding. Chapuy:BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sobi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Ars tempi: Honoraria; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Regeneron: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; ADC: Consultancy, Membership on an entity's Board of Directors or advisory committees; Ono: Honoraria; Sandoz: Honoraria; KML: Honoraria; AstraZeneca: Honoraria; Kite/Gilead: Honoraria, Research Funding. von Tresckow:Pentixapharm: Consultancy; Novartis: Consultancy, Honoraria, Other: Travel Support, Research Funding; MSD: Consultancy, Honoraria, Other: Travel Support, Research Funding; Pfizer: Consultancy; Takeda: Consultancy, Honoraria, Other: Travel Support, Research Funding; Noscendo: Consultancy; BMS/Celgene: Consultancy, Honoraria; Cerus: Consultancy; Incyte: Consultancy, Honoraria; Allogene: Consultancy; IQVIA: Consultancy; Gilead Kite: Consultancy, Other: Travel Support; Miltenyi: Consultancy; Amgen: Consultancy; Pierre Fabre: Other: Travel support; Roche: Consultancy, Honoraria, Other: Travel Support; AbbVie: Other: Travel Support; AstraZeneca: Honoraria, Other: Travel Support; Lilly: Consultancy, Honoraria, Other: Travel Support. Einsele:Janssen: Honoraria, Other: Consulting or advisory role, Travel support, Research Funding; Amgen: Honoraria, Other: Consulting or advisory role, Travel support, Research Funding; Takeda: Honoraria, Other: Consulting or advisory role, Travel support; GlaxoSmithKline: Honoraria, Other: Consulting or advisory role, Travel support, Research Funding; Sanofi: Honoraria, Other: Consulting or advisory role, Travel support, Research Funding; Novartis: Honoraria, Other: Consulting or advisory role, Travel support; Bristol Myers Squibb/Celgene: Honoraria, Other: Consulting or advisory role, Travel support, Research Funding. Duell:MorphoSys AG, Regeneron: Research Funding.
