A Phase 3 Study of Tafasitamab Plus Lenalidomide in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (firmMIND)
Bibliographic record
Abstract
Background: Diffuse large B-cell lymphoma (DLBCL) is an aggressive form of lymphoma and the most common subtype of non-Hodgkin's lymphoma representing ~31% of all cases (Thandra KC, et al. Med Sci. 2021;9:5). Treatment with the anti-CD20 monoclonal antibody (mAb) rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone is the standard first-line therapy; however, 30-40% of patients experience relapsed or refractory (R/R) disease (Harris LJ, et al. Int J Mol Sci. 2020;21:8553). High-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) improve outcomes for patients with R/R disease; however, many patients are ineligible for HDC/ASCT owing to age, comorbidities, or frailty. Therapies targeting CD19, which is expressed on normal and malignant B cells and regulates proliferation, have also shown promising results in the treatment of R/R DLBCL. Tafasitamab is a humanized mAb targeting CD19, and Fc-engineered for increased affinity to Fcγ receptors on immune effector cells. Preclinical data showed that tafasitamab acts synergistically with the immune modulator lenalidomide. The phase 2 L-MIND study (NCT02399085) evaluated tafasitamab plus lenalidomide in patients with R/R DLBCL who were ineligible for HDC/ASCT. The objective response rate (ORR) was 57.5% (n=46/80), including a complete response in 40.0% (n=32/80) of patients. Responses were durable, with a median duration of response of 43.9 months at ≥35 months of median follow-up. Based on the results of L-MIND, tafasitamab plus lenalidomide was approved in the United States (accelerated approval), Canada and European Union (conditional approval), and other countries for adult patients with R/R DLBCL who are not eligible for ASCT. The firmMIND study (NCT05429268) is a post-authorization commitment study to confirm the efficacy, safety, and overall benefit/risk of the combination of tafasitamab plus lenalidomide in R/R DLBCL. Study Design and Methods: In this single-arm, multicenter, open-label, phase 3 study, patients will receive tafasitamab (12 mg/kg IV on days 1, 8, 15, and 22 of a 28-day cycle [cycles 1-3] with an additional loading dose on cycle 1 day 4, then days 1 and 15 [cycles 4-12]) plus lenalidomide (25 mg orally once daily, days 1-21/cycle) for 12 cycles, followed by tafasitamab monotherapy (in patients with stable disease or better) until progressive disease, withdrawal of consent, or unacceptable toxicity. Radiologic assessments will be performed at baseline, cycles 3, 5, 7, 10, 13, 16, 19, 22, 25, and then every 12 months until end of treatment (EOT). Positron emission tomography will be performed at baseline and then throughout treatment to EOT. Eligible patients are ≥18 years of age with a histologically confirmed diagnosis of DLBCL, T-cell/histiocyte-rich large BCL, Epstein-Barr virus-positive DLBCL of the elderly, grade 3b follicular lymphoma, composite lymphoma with a DLBCL component and subsequent DLBCL relapse, or histological transformation of a low-grade lymphoma into DLBCL. Patients must have measurable R/R disease; received at least 1 but no more than 3 previous systemic regimens for DLBCL, one of which must have been an anti-CD20-targeted therapy; be ineligible for intensive salvage therapy including ASCT; ECOG performance status of 0-2; and adequate organ function. Patients with any other lymphoid neoplasm including primary mediastinal large B-cell lymphoma, Burkitt lymphoma, DLBCL with simultaneous MYC2, BCL2, and/or BCL6 translocations, or prior central nervous system lymphoma, prior treatment with CD19-targeted therapy or an immunomodulator, ASCT ≤3 months before study start, primary refractory DLBCL (disease progressing <6 months of first-line treatment), or prior allogenic stem cell transplantation are excluded. The primary endpoint is ORR assessed by an independent review committee (IRC) based on the Lugano criteria (Cheson BD, et al. J Clin Oncol. 2014;32:3059-3068). Secondary endpoints include safety, IRC-assessed progression-free survival, and overall survival. It is planned to enroll 81 patients into the study.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.004 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".