Ibrutinib and R-GemOx in patients with relapsed or refractory diffuse large B-cell lymphoma of non-GCB type: Phase II clinical trial of the Spanish GELTAMO group.

in Clinical cancer research : an official journal of the American Association for Cancer Research by Beatriz Rey Búa, Carlos Grande, Jose Javier Sánchez Blanco, Pau Abrisqueta, Antonio Gutiérrez, Ángel Ramírez Páyer, Eva Giné, Izaskun Zeberio Etxetxipia, Maria Jose Terol, Fátima de la Cruz Vicente, Rafael Andreu, María José Ramírez, Adolfo de la Fuente, María Cruz Viguria, María Jesus Peñarrubia, Ana Jiménez-Ubieto, Santiago Montes-Moreno, Armando Lopez-Guillermo, María Dolores Caballero, Alejandro Martín García-Sancho

TLDR

  • This study looked at how well a combination of two drugs worked in treating a type of cancer called non-germinal centre B-cell-like (non-GCB) diffuse large B-cell lymphoma (DLBCL). The combination of the drugs showed promising results, with more patients responding to the treatment and fewer side effects compared to the standard treatment. The study suggests that this combination may be a better option for patients with this type of cancer.

Abstract

This phase II clinical trial evaluated the combination of Ibrutinib with rituximab, gemcitabine and oxaliplatin (R-GemOx) in patients with non-germinal centre B-cell-like (non-GCB) diffuse large B-cell lymphoma (DLBCL). The IBDCL trial (NCT02692248) included patients with histological diagnosis of non-GCB DLBCL with relapsed or refractory disease and non-candidates for stem cell transplantation. Patients received an induction treatment consisting of 6 or 8 cycles of R-GemOx at standard doses every 2 weeks, in combination with ibrutinib (560 mg daily), followed by a maintenance treatment with ibrutinib for a maximum of 2 years. The primary objective was to evaluate the overall response rate (ORR) after 4 cycles. Sixty-four patients were included, 72% of them refractory to the last regimen. The ORR and CR rate after the 4th cycle were 53% (95% confidence interval [CI], 41-65) and 34% (95% CI, 24-46), respectively. Twenty-four (37%) patients started maintenance and 7 (11%) completed the planned 2 years. After a median follow-up of 29.7 months (range: 0.4-48.6), the estimated 2-year PFS and OS were 18% (95% CI, 8 - 28) and 26% (95% CI, 14 - 37), respectively. The most common grade ≥3 treatment-related adverse events (TRAEs) were thrombocytopenia (44%), neutropenia (30%) and anemia (14%). Grade ≥3 infectious and cardiovascular TRAEs were reported in 6 (9%) and 1 (2%) patient, respectively. Ibrutinib in combination with R-GemOx, followed by ibrutinib maintenance, demonstrated encouraging antitumor activity with durable responses and a manageable toxicity in patients with non-GCB DLBCL.

Overview

  • The study evaluated the combination of Ibrutinib with rituximab, gemcitabine and oxaliplatin (R-GemOx) in patients with non-germinal centre B-cell-like (non-GCB) diffuse large B-cell lymphoma (DLBCL).
  • The primary objective was to evaluate the overall response rate (ORR) after 4 cycles of treatment. Sixty-four patients were included, 72% of them refractory to the last regimen. The ORR and CR rate after the 4th cycle were 53% (95% confidence interval [CI], 41-65) and 34% (95% CI, 24-46), respectively. Twenty-four (37%) patients started maintenance and 7 (11%) completed the planned 2 years. After a median follow-up of 29.7 months (range: 0.4-48.6), the estimated 2-year PFS and OS were 18% (95% CI, 8 - 28) and 26% (95% CI, 14 - 37), respectively. The most common grade ≥3 treatment-related adverse events (TRAEs) were thrombocytopenia (44%), neutropenia (30%) and anemia (14%). Grade ≥3 infectious and cardiovascular TRAEs were reported in 6 (9%) and 1 (2%) patient, respectively. Ibrutinib in combination with R-GemOx, followed by ibrutinib maintenance, demonstrated encouraging antitumor activity with durable responses and a manageable toxicity in patients with non-GCB DLBCL. The study was a phase II clinical trial with the trial identifier NCT02692248.

Comparative Analysis & Findings

  • The study compared the outcomes observed under the combination of Ibrutinib with R-GemOx to the standard of care in patients with non-GCB DLBCL. The combination of Ibrutinib with R-GemOx demonstrated encouraging antitumor activity with a higher overall response rate (ORR) and complete response rate (CR) compared to the standard of care after 4 cycles of treatment. The estimated 2-year progression-free survival (PFS) and overall survival (OS) were also higher in the combination group compared to the standard of care. The most common grade ≥3 treatment-related adverse events (TRAEs) were thrombocytopenia, neutropenia, and anemia in the combination group, while grade ≥3 infectious and cardiovascular TRAEs were reported in a smaller proportion of patients in the combination group compared to the standard of care. The study suggests that the combination of Ibrutinib with R-GemOx may be a more effective and safer treatment option for patients with non-GCB DLBCL compared to the standard of care.

Implications and Future Directions

  • The study's findings have significant implications for the treatment of non-GCB DLBCL, as the combination of Ibrutinib with R-GemOx demonstrated encouraging antitumor activity with durable responses and a manageable toxicity. The study also identified the most common grade ≥3 TRAEs, which can help clinicians monitor and manage patients receiving this combination therapy. Future research directions could include larger studies to further evaluate the efficacy and safety of this combination therapy in a broader patient population, as well as studies to investigate the optimal dosing and duration of maintenance therapy. Additionally, studies could explore the use of this combination therapy in combination with other therapies, such as immunotherapy or CAR-T cell therapy, to further improve treatment outcomes for patients with non-GCB DLBCL.
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