-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

1771 Tafasitamab and Lenalidomide in Relapsed/Refractory B-Cell Lymphoma: A Multicenter Retrospective Real-World-Study of Patients from Germany and Austria

Program: Oral and Poster Abstracts
Session: 627. Aggressive Lymphomas: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Lymphomas, B Cell lymphoma, Combination therapy, Diseases, Therapies, Lymphoid Malignancies, Adverse Events
Saturday, December 9, 2023, 5:30 PM-7:30 PM

Anna Ruckdeschel, MD1*, Koemm Sabrina1*, Max S. Topp, MD1*, Richard Greil, MD2, Thomas Melchardt, MD2*, Georg Lenz3, Andrea Kerkhoff, MD4*, Evgenii Shumilov, MD4*, Georg Hess5*, Marta Baumgaertner5*, Lorenz Thurner, MD6, Igor Age Kos7*, Stephanie Mayer8*, Francis A. Ayuk, MD9*, Rolf Krause9*, Marco Herling10*, Vladan Vucinic, M.D.11*, Claudia Chapuy12*, Gerald Illerhaus, MD13, Markus Knott, MD13*, Andreas Viardot, MD PhD14, Alexander Grunenberg14*, Sascha Dietrich, MD15*, Leandra Caille15*, Mareike C. Tometten16*, Hyunyee Rosa Cho16*, Julia Scholz17*, Fabian Mueller, MD17*, Katharina Prochazka18*, Bjoern Chapuy, MD19, David Böckle19*, Bastian von Tresckow, MD20, Natalie Schub21*, Götz Gelbrich22*, Hermann Einsele, MD, PhD23* and Johannes Duell, MD1*

1Department of Internal Medicine II, Hematology and Oncology, University Hospital Wuerzburg, Wuerzburg, Germany
2Paracelsus Medical University, Department of Internal Medicine III with Hematology, Medical Oncology, Hemostaseology, Infectiology and Rheumatology, Oncologic Center, Salzburg Cancer Research Institute - Laboratory for Immunological and Molecular Cancer Research (SCRI-LIMCR), Salzburg, Austria
3Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital Muenster, Muenster, Germany
4Medical Department A for Hematology, Oncology, and Pneumology, University Hospital Muenster, Muenster, Germany
5University Clinic Mainz, Mainz, Germany
6Department of Internal Medicine 1, Oncology, Hematology, Clinical Immunology, and Rheumatology, Saarland University Medical Center, Homburg/Saar, Germany
7Department of Internal Medicine 1, Oncology, Hematology, Clinical Immunology, and Rheumatology, Saarland University Medical Center, Homburg, Germany
8Universitätsklinikum Regensburg, Regensburg, DEU
9Department of Stem Cell Transplantation with Research Department Cell and Gene Therapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
10Department of Hematology, Cellular Therapy, Hemostaseology and Infectious Diseases, University Leipzig Medical Center, Leipzig, Germany
11Department of Hematology, Cellular Therapy, Hemostaseology and Infectious Diseases, University of Leipzig, Leipzig, Germany
12University Medical Center Göttingen, Georg-August-Universität Göttingen, Göttingen, Germany
13Department of Hematology/Oncology and Palliative Care, Klinikum Stuttgart, Stuttgart, Germany
14Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany
15Heidelberg University Hospital, Heidelberg, DEU
16RWTH Aachen University, Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty, Aachen, Germany
17Department of Internal Medicine 5, Hematology and Oncology, University Hospital of Erlangen, Erlangen, Germany
18Medical University of Graz, Graz, AUT
19Department of Hematology, Oncology and Tumor Immunology, Charité - University Medical Center Berlin, Campus Benjamin Franklin, Berlin, Germany
20Department of Hematology and Stem Cell Transplantation, West German Cancer Center Essen, Essen, Germany
21University Hospital Schleswig-Holstein, Campus Kiel, Division For Stem Cell Transplantation and Immunotherapy, 2nd Department of Medicine, Kiel, Germany
22Institute of Clinical Epidemiology and Biometry, University of Wuerzburg, Würzburg, DEU
23Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany

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. 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: Amgen: Honoraria, Other: Consulting or advisory role, Travel support, Research Funding; Takeda: Honoraria, Other: Consulting or advisory role, Travel support, Research Funding; GlaxoSmithKline: Honoraria, Other: Consulting or advisory role, Travel support, Research Funding; Sanofi: Honoraria, Other: Consulting or advisory role, Travel support, Research Funding; Janssen: 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.

*signifies non-member of ASH