Abstract
Introduction
Epidemiological data in Brazil about Mantle Cell Lymphoma (MCL) are scarce. Recently, we could observe improvement in survival outcomes with the inclusion of rituximab maintenance in therapy schemes, use of proteasome inhibitors and Bruton's tyrosine kinase inhibitors (BTKi). Considering this, there is a need to understand real world patterns, barriers, treatments, and outcomes among Brazilian MCL patients. Thus, the aim of this study is to evaluate clinical parameters, outcomes considering clinical profile, types of treatments, rate of Autologous Stem Cell Transplantation (ASCT) as consolidation strategy, as well as to evaluate the survival of refractory/relapsed (R/R) patients in the pre BTKi era.
Methods
This is an observational retrospective cohort study of consecutive patients in a single institution (HEMOMED) from January 2009 to December 2020. Inclusion criteria: Adult male or female patients ≥ 18 years of age and MCL diagnosis. Exclusion criteria: enrolment in studies that prohibit any participation in this Observational Study.
Results
Forty-seven patients were enrolled, 38 (80.9%) were male patients. Median age was 65 (35-84) years old and 20 (42.6%) were retired workers. From 42 patients with available data, 28/42 (66.6%) presented ECOG > 1 and 37/42 (88%) advanced disease. In 30 patients with available data, 20/30(66.6%) had high risk MIPI. Three of 47 patients (6.3%) had indolent presentation and watchful waiting was considered, however all three patients required treatment - median time to treatment 23.4 (95IC 5.9 - 27.7) months and 1/47 (2.1%) patient was considered for exclusive palliative regimen. Thus, in 43 patients, 16 (37.2%) were considered candidates for ASCT in diagnosis.
The first-line treatment were: RCHOP 17/43 (39.5%), R-DHAP/R-DHAOX 9/43(20.9%), R-HyperCVAD 4/43 (9.3%) and BR 4/43 (9.3%). Complete Response and overall response (OR) were: 28/43 (65.1%) and 32/44(74.4%), respectively. Sixteen/43 (37.2%) received rituximab maintenance. Only 9(56.2%) of 16 candidates were submitted to ASCT consolidation, seven patients that were not submitted to ASCT: 2 did not achieve OR after induction, 1 died due to COVID-19 after C2 RDHAOX, 1 refused due to the risk of COVID-19, 1 was not submitted by another ASCT team due to Partial Response, 1 was not submitted due to delay and 1 presented stem cell mobilization failure after R HyperCVAD.
The three-year OS and PFS were 60% and 44%, respectively. Median overall survival (OS) and progression-free survival (PFS) were 39.5 (95CI 33.9 - 45.1) and 28.5 (95CI 17.6-39.3) months, respectively. Patients with OR after first-line treatment presented better OS: 67.9 (95CI 40.6-95.3) compared to patients with stable disease or progression 19.4 (95IC 18-20.8) months, p < 0.01. In addition, in the group with OR, rituximab maintenance significantly improved median PFS: 38.23 (95CI 32.39- 44) compared to 31.4 (95IC 9.5- 44) months, p=0.039. (FIGURE A) Patients that received ASCT compared to the ones that were not submitted to ASCT presented 3 years OS of 78% compared to 59%, respectively. In this, group, median OS was not reached compared to other patients with median of 38.2 (95CI 28.6-47.9) months, p=0.06 (FIGURE B).
Twenty-two R/R MCL patients were studied. Ten/22 (45.4%) presented early progression disease (POD24). Cytarabine regimen was the most frequently used 6/22(27.2%) with 3/22 patients (13.4%) receiving bendamustine. OR was achieved in 6/22 (27.2%) patients. Allogeneic ASCT was used in 2 patients. The three-year OS and PFS after R/R were: 29% and 11%, respectively. Median OS and PFS were 23.2 (95CI 8.4 - 37.9) and 6.9 (95CI 3.1-10.6) months, respectively.
Discussion
It is possible to observe in this small cohort that the majority of patients present high risk MIPI, with only 56.2% of candidates submitted to ASCT consolidation. It was also possible to observe the impact of COVID-19 in these patients. OR after first-line treatment was related to a good prognosis. The inclusion of rituximab in the last years, as maintenance therapy after first-line treatment in patients with OR, improved PFS. Moreover, it is important to highlight that the approval of mandatory reimbursement for BTKis in R/R MCL for the private sector by Agência Nacional de Saúde Suplementar (ANS) in Brazil occurred on February 2021, so our data for R/R MCL showed poor prognosis, like already indicated by other published retrospective data in the pre BTKi era.
Disclosures
Bellesso:AstraZeneca: Research Funding.
