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Tafasitamab With or Without Lenalidomide and R-CHOP Tolerable for Patients With DLBCL
A phase 1B study shared at the 2021 Annual American Society of Hematology (ASH) Meeting reported on the safety and tolerability of tafasitamab in newly diagnosed diffuse large B-cell lymphoma (DLBCL).
Tafasitamab is an anti-CD19 monoclonal antibody that enhances antibody-depedent cellular cytotoxicity and phagocytosis. In July 2020, it was approved by the FDA in combination with lenalidomide for the treatment of patients with relapsed/refractory (R/R) DLBCL who are ineligible for autologous stem cell transplant.
Thus, David Belada, MUDr, PhD, 4th Department of Internal Medicine – Hematology, University Hospital and Faculty of Medicine, Hradec Králové, Czech Republic, and co-investigators, aimed to evaluate the safety and tolerability of tafasitamab alone or tafasitamab plus lenalidomide in addition to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with newly diagnosed DLBCL.
Between December 2019 and August 2020, 83 patients with treatment-naïve DLBCL, who had an international prognostic index (IPI) 2–5, and an Eastern Cooperative Oncology Group performance status (ECOG PS) 0–2, were screened in 9 countries across 34 sites in Europe and the United States were enrolled.
Out of 83 total patients (median age 64.5), 66 were randomized to receive either 6 21-day cycles of R-CHOP plus tafasitamab (Arm A, n=33), or tafasitamab plus lenalidomide and R-CHOP (Arm B, n=33). Patients were excluded from the study if they had known double- or triple-hit transformed lymphoma, and it was mandatory for franulocyte colony-stimulating factor and venous thromboembolism prophylaxis. The data cutoff was March 13, 2021. Many patients had high-risk disease, including IPI 2 in 24 (36.4%) patients, IPI 3 in 29 (43.9%), IPI 4 in 11 (16.7%), IPI 5 in 2 (3%), and ECOG PS ≥2 in 6 (9.1%). Out of the 66 randomized patients, 62 (93.9%) had Stage III/IV disease, and 29 (43.9%) had bulky disease.
The primary safety endpoint was incidence of treatment-emergent adverse events (TEAEs). The secondary endpoints included overall response rate (ORR), positron emission tomography (PET) complete response (CR) rate, and partial response (PR) at the end of treatment (EOT). Tumor measurements by PET/CT or PET/MRI at EOT were performed according to Lugano 2014 criteria within 6±2 weeks after day 21 of the patient’s last treatment cycle.
Every patient in the study experienced at least 1 TEAE. The most common grade ≥3 TEAEs by stem organ class were blood and lymphatic disorders (81.8% patients overall) experienced by 24 (72.2%) patients in Arm A and 30 (90.9%) patients in Arm B. Grade ≥3 neutropenia and thrombocytopenia were seen in 19 (57.6%) and 4 (12.1%) patients in Arm A, and 28 (84.8%) and 12 (36.4%) patients in Arm B, respectively. Grade ≥3 febrile neutropenia was experienced by 6 (18.2%) patients in both arms. Grade ≥3 infusion-related reactions to both rituximab and tafasitamab occurred in just 1 (3%) patient in Arm B. Seven (21.2%) patients in Arm A and 9 (27.3%) patients in Arm B had a grade ≥3 infection and/or infestation. Serious TEAEs occurred in 14 (42.4%) patients in Arm A and 17 (51.5%) patients in Arm B. In Arm A and Arm B, 2 patients and 1 patient discontinued the treatment due to TEAEs, respectively. There were 4 deaths unrelated to tafasitamab and/or lenalidomide. The ORR at EOT was seen in 25 patients (75.8%, 95% CI, 57.7-88.9) in Arm A, and 27 patients (81.8%, 95% CI, 64.5-93) in Arm B.
“These data suggest that both regimens are tolerable and do not impair dosing and scheduling of R-CHOP. Toxicities were similar to those expected with R-CHOP with or without lenalidomide. With tumor follow-up still ongoing, the ORR at EOT suggests that patients with treatment-naïve DLBCL may achieve clinically meaningful efficacy (with) tafasitamab and lenalidomide in addition to standard treatment,” concluded Dr Belada and co-investigators.
A phase 3, multicenter, randomized, double-blind, placebo-controlled trial is currently recruiting high-intermediate or high-risk DLBCL patients to assess the efficacy and safety of R-CHOP plus tafasitamab and lenalidomide versus R-CHOP alone.—Emily Bader
Belada D, Kopeckova K, Burgues JMB, et al. First-mind: Primary analysis from a phase IB, open-label, randomized study to assess safety of tafasitamab or tafasitamab + lenalidomide in addition to R-CHOP in patients with newly diagnosed diffuse large B-cell lymphoma. Presented at: the 2021 ASH Annual Meeting; Dec. 11-14; 2021; Abstract 3556.
