Tafasitamab-containing regimens in relapsed/refractory diffuse large B-cell lymphoma: A real-world retrospective case series Free

Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (Br J Haematol 2024;205(6):2163-2174). Although first-line treatment with R-CHOP achieves remission in a substantial proportion of patients, many ultimately develop relapsed or refractory (R/R) disease. Currently, therapeutic options for these patients remain limited, particularly for those who are ineligible for stem cell transplantation (J Clin Oncol 2014;32(10):1066-73; Blood 2022;140 Suppl:12089). Tafasitamab is a humanized, Fc-enhanced monoclonal antibody targeting CD19 (Blood 2024;143(3):258-271); it has been approved in combination with lenalidomide for the treatment of adults with R/R DLBCL, representing the first second-line therapy approved for this patient population (Drugs 2020;80(16):1731-1737). However, real-world evidence regarding the effectiveness and safety of tafasitamab-containing regimens, particularly with novel combinations incorporating radiotherapy (RT) or PD-1 inhibitors, is scarce in the Chinese population. This case series characterizes the clinical outcomes of tafasitamab-containing therapies in routine clinical practice.

Methods: We retrospectively analyzed five consecutive R/R DLBCL patients (median age 81 years, range 50-87) with poor baseline PS (ECOG ≥2: 3/5 patients; ECOG 3: 1 patient) and high tumor burden treated between Jan 2024-Jul 2025. All were heavily pretreated (median prior lines: 4; range 2-7) and transplant-ineligible. Tafa combinations included RT (n=1) or PD-1 inhibitors (tislelizumab, n=2). Outcomes included clinical response (Lugano 2014) and safety (CTCAE v5.0).

Results: Cohort Vulnerability:

Patients exhibited high-risk features: advanced age (≥80 years: n=3), ECOG ≥2 (n=3), high IPI (≥3: n=2), double-expressor lymphoma (n=2), bone marrow involvement (n=2), and pre-existing infection (n=1). Five patients (P1-P5) were included, with details as follows:

P1: 81-year-old female with stage IVA germinal center B-cell (GCB) DLBCL (ECOG 2). After 4 prior therapies with partial response (PR), she achieved stable disease with tafasitamab + lenalidomide after 2 cycles, with only grade 1 leukopenia and grade 2 thrombocytopenia.

P2: 87-year-old female with stage IIB non-GCB DLBCL (ECOG 2, IPI 3, MYC/BCL2 double expression). Uncontrolled after 4 prior regimens, she achieved PR with tafasitamab + lenalidomide + radiotherapy + zanubrutinib (maintained through cycle 3), but she had pre-existing pulmonary infection, recurrent infections, and grade 4 neutropenia. Subsequent treatment consisted of a regimen combining tafasitamab and adoptive NK cell-based immunotherapy, and progressed in cycle 4 after switching regimens.

P3: 68-year-old male with stage IVB non-GCB DLBCL (ECOG 0, IPI 2). After partial metabolic response to first-line therapy, he achieved a complete response (CR) with tafasitamab + lenalidomide after 1 cycle, with no treatment-related adverse events (TRAEs).

P4: 82-year-old female with stage IVB non-GCB DLBCL (ECOG 3, IPI 5, MYC/BCL2 double expression). Previously treated with ZRD, she received tafasitamab with no TRAEs; treatment was ongoing at analysis, with response unassessed.

P5: 50-year-old female with stage IVB non-GCB DLBCL (transformed from mucosa-associated lymphoid tissue lymphoma; ECOG 0, IPI 2). She achieved CR with tafasitamab + lenalidomide + tislelizumab after 2 cycles, maintaining remission for 6 additional cycles with no TRAEs over 8 total cycles.

These patients had an advanced average age of 81 years (range: 50-87), with 80% at stage IV and generally poor baseline status. However, in real-world practice, flexible tafa-len-based combinations (including PD-1 inhibitors, radiotherapy, or BTK inhibitors) yielded favorable outcomes (best ORR: 75%, CR rate: 50%), with good overall safety. Progression-free survival was maintained in 80% (4/5) of patients during the follow-up period.

Conclusion: This real-world series demonstrates that tafa-containing regimens exhibit clinically meaningful activity in extremely frail, heavily pretreated R/R DLBCL patients with poor baseline PS (ECOG ≥2 in 80%). Critically, combinations incorporating radiotherapy or PD-1 inhibition (tislelizumab) yielded significant responses. These novel combinations warrant prospective investigation in high-risk, poor-PS R/R DLBCL populations where effective, tolerable therapies are urgently needed.