In this study, we revisited 28 patients from 12 centers in Brazil. One patient included in the RTXM83-CHOP group was excluded because the corresponding research center declined to participate, and we used data from 27 participants: 15 (55.6%) and 12 (44.4%) in the RTXM83-CHOP and R-CHOP groups, respectively. The distribution of study participants across the centers is detailed in Supplementary Materials Table S1. The overall median follow-up period was 77.0 months, which underscores the efficacy of this study in evaluating long-term outcomes. The detailed follow-up data are presented in Table 1. The demographic data and DLBCL history are depicted in Table 2.

Five patients experienced late AEs of interest between the conclusion of the RTXM83-AC-01-11 study and the last assessment in the LB2002 study (Table 3).

Detailed descriptions of AEs in each patient and the treatment groups are presented in Table 4. Three patients were treated pharmacologically for neutropenia, immune system disorders, and severe infections, which led to various outcomes. Two of these patients experienced recovery or resolution; however, one case of necrotizing fasciitis led to sequelae. Patient 2 died after a febrile neutropenia event. However, the correlation between these events could not be established in the medical records owing to the unknown cause of death.

Additionally, a patient with endometrial adenocarcinoma successfully underwent hysterectomy and lymphadenectomy and recovered without sequelae; another patient with prostate cancer experienced sequelae post-laparoscopic radical prostatectomy.

In this sub-analysis of the RTXM83-AC-01-11 study, major differences in the frequency or severity of common AEs were not identified between treatments (Supplementary Materials Tables S2 and S3).

After 77 months of median follow-up, the disease progression was detected in 6.7% (1 of 15 patients) of the RTXM83-CHOP group and 41.7% (5 of 12 patients) of the R-CHOP group. This difference was reflected in the PFS rates; Kaplan-Meier analysis revealed a higher rate of PFS was detected in RTXM83-CHOP (93.3%) than in R-CHOP (50%). The median PFS was 40.5 months in the R-CHOP group, while the median PFS had not been achieved in the RTXM83-CHOP group (Fig. 2). The response rates of the Brazilian cohort are detailed in Supplementary Materials Fig. S1.

Kaplan-Meier estimates for the cumulative probability of progression-free survival during the final assessment for patients receiving RTXM83-CHOP or R-CHOP treatment. The number of patients at risk at each time point is indicated (bottom). CI confidence interval, NR not reached

Furthermore, during our comprehensive follow-up, the RTXM83-CHOP group exhibited a 100% cumulative OS rate with no fatalities, whereas, the R-CHOP group exhibited a cumulative OS rate of 64.2%, with 4 of 12 included patients deceased. Consequently, the median OS was not achieved in either group (Fig. 3).

Kaplan-Meier estimates for the cumulative probability of overall survival during the final assessment of patients treated with RTXM83-CHOP or R-CHOP. The number of patients at risk at each time point is indicated (bottom). CI confidence interval, NR not reached

The waterfall chart (Fig. 4) summarizes the monitoring of individual patients and indicates the occurrence of late AEs of interest, disease progression, and death.

Waterfall chart illustrates the follow-up time in the LB2002 study, between the diagnosis in the RCT and extension phase. The time of analyzing disease progression, late adverse events of interest, and death is indicated. Each bar represents a patient, separated according to the treatment group, R-CHOP or RTXM83-CHOP. RCT randomized clinical trial

Regarding causes of death, patient 1 died from febrile neutropenia/septic shock after 3.4 months of follow-up. Patient 2 was presumed to have died because of neutropenia and/or active disease 12.4 months after recruitment in this study; however, specific details were not fully documented. Patient 3 died because of disease progression, with specific involvement of the lung and rectal areas after 13.6 months of follow-up. Patient 4 died from septic shock after 17.0 months of follow-up. The death of patient 1 was possibly related to rituximab and definitively associated with CHOP. The correlation of the deaths in patients 2, 3, and 4 with treatments has not been established.

Splenectomy appeared ineffective in the RTXM83-CHOP-treated patient with relapsed disease. In the R-CHOP group, four non-transplant candidates received various second-line treatments: GEMOX (gemcitabine, oxaliplatin), R-ICE (rituximab, ifosfamide, carboplatin, and etoposide) + GEMOX, ICE (ifosfamide, carboplatin, and etoposide), and ICE + DHAP (cisplatin, cytarabine, and dexamethasone). A patient received R-GDP (rituximab, gemcitabine, cisplatin, and dexamethasone) followed by autologous transplant therapy.