Portuguese real-world experience with ibrutinib for the treatment of relapsed/refractory mantle cell lymphoma

Catarina Fernandes^1*Rita Costa e Sousa²Pedro Santos¹Cátia Almeida²Adriana Roque²Ana Luísa Pinto³Joaquim Monteiro³Anabela Neves⁴Maria João Ramos⁵Rita Coutinho^5,6,7Filipa Mousinho⁸Mariana Leal Fernandes⁹Margarida Badior¹⁰Cristina João^11,12Sónia Leocádio¹¹Ana Tomé¹³Margarida Carrolo¹⁴Sara Simões Dias¹²Maria Gomes da Silva¹João Paulo Fernandes¹⁴

• ¹Hematology Department, Instituto Portugues de Oncologia de Lisboa Francisco Gentil EPE, Lisbon, Portugal
• ²Clinical Hematology Department, Unidade Local de Saude de Coimbra, Coimbra, Portugal
• ³Hematology Department, Unidade Local de Saude de Sao Joao, Porto, Portugal
• ⁴Hematology Department, Unidade Local de Saude da Arrabida, Setúbal Municipality, Portugal
• ⁵Hematology Department, Unidade Local de Saude de Santo Antonio EPE, Porto, Portugal
• ⁶Department of Hematology and Bone Marrow Transplantation, Instituto Portugues de Oncologia do Porto Francisco Gentil EPE, Porto, Portugal
• ⁷Universidade do Porto Instituto de Ciencias Biomedicas Abel Salazar, Porto, Portugal
• ⁸Hematology Department, Unidade Local de Saude de Lisboa Ocidental, Lisbon, Portugal
• ⁹Hematology Department, Unidade Local de Saude Sao Jose, Lisbon, Portugal
• ¹⁰Hematology Department, Unidade Local de Saude de Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Portugal
• ¹¹Hemato-Oncology Unit, Fundacao Champalimaud, Lisbon, Portugal
• ¹²Universidade Nova de Lisboa Medical School, Lisbon, Portugal
• ¹³Hemato-Oncology Department, Unidade Local de Saude de Almada-Seixal, Almada, Portugal
• ¹⁴Hemato-Oncology Unit, Hospital CUF Descobertas, Lisbon, Portugal

Background: Mantle cell lymphoma is usually characterized by an aggressive and recurrent course. Clinical trials and real-world series have demonstrated clinical benefits with the use of ibrutinib as a second-line treatment, compared to later relapses. Objective: To evaluate the Portuguese experience with the use of ibrutinib in patients with relapsed or refractory mantle cell lymphoma since its approval in the country. Methods: A multicenter retrospective cohort of patients with mantle cell lymphoma who received ibrutinib between 2015 and 2020 was studied. Results: Ninety-five patients treated at 11 hospitals were included. At the ibrutinib starting date, 51% of patients had high-risk simplified mantle cell lymphoma international prognostic index, 9% had central nervous system involvement, and 21% had Eastern Cooperative Oncology Group performance status ≥2. The median treatment duration was 10 (<1-75) months. The overall response rate was 66%, including 36% with complete responses. After 18 months of follow-up, seventy-two patients (76%) had discontinued ibrutinib, mainly due to progressive disease (61%) and toxicity (21%). At the last follow-up, 24% of patients were still on ibrutinib, and 60% had died, mostly (65%) due to lymphoma progression. Conclusions: In this real-world series, the safety of ibrutinib is similar to the results described in clinical trials. However, new strategies are needed for the treatment of acquired resistance to ibrutinib.