Page 181 - Haematologica Vol. 110 - January 2025

LETTER TO THE EDITOR
Rituximab maintenance after bendamustine-based treatment for follicular lymphoma and mantle cell lymphoma may exert a negative influence on SARS-CoV-2 infection outcomes
Different chemoimmunotherapy strategies have been em- ployed as first-line treatment for patients diagnosed with mantle cell lymphoma (MCL) and follicular lymphoma (FL). Cyclophosphamide-based regimens (RCVP/RCHOP) or ben- damustine-containing protocols followed by the option of maintenance treatment with an anti-CD20 agent, are the approaches most commonly preferred. We analyzed out- comes of SARS-CoV-2 infection in 215 patients diagnosed with FL or MCL treated with chemoimmunotherapy and subsequent rituximab maintenance in six tertiary Spanish centers. Of note, temporary interruptions or dose delays during maintenance due to SARS-CoV-2 infection were documented in 44% of patients, with definitive suspen- sion of treatment in 22% of patients. Patients receiving maintenance treatment after bendamustine-based regi- mens presented inferior SARS-CoV-2 infection outcomes compared to patients in maintenance after cyclophospha- mide-containing regimens. The former cohort presented higher rates of severe disease, increased hospitalizations, and mortality related to the SARS-CoV-2 infection, leading to a shorter overall survival (OS), compared to the cyclo- phosphamide cohort.
R-CHOP/R-CVP treatment strategies have been widely employed as first-line immunochemotherapy regimens for indolent B-cell non-Hodgkin lymphomas (NHL).1 While two randomized clinical trials (Study group indolent Lymphomas, StiL, and BRIGHT) demonstrated enhanced progression-free survival (PFS) and reduced toxicity with bendamustine-rit- uximab (BR) compared with RCHOP/RCVP,2,3 “real-world” evaluations of the BR approach have shown a trend for increased hospitalizations and infections, albeit without an impact on OS.4 Moreover, in the GALLIUM study, evalu- ating the combination of rituximab or obinutuzumab with CHOP, CVP or bendamustine for previously untreated FL patients, a higher rate of infections was reported in the bendamustine arm compared to the CHOP/CVP arm. Also, there was a higher rate of infections in the bendamustine arm, independent of the combination with obinutuzumab or rituximab, and this was particularly evident during the maintenance and follow-up phases. Nevertheless, CHOP was associated with higher rates of grade 3 neutropenia during the induction.5 Rituximab maintenance (RM) after front-line treatment has significantly improved PFS in FL,6 and both PFS and OS in MCL.7,8 However, the consensus on the use of RM following front-line BR remains elusive,
primarily due to the absence of randomized data demon- strating a clear benefit for RM in this particular setting. While retrospective data suggest the potential safety of RM after BR,9 it has not been systematically evaluated in the context of the SARS-CoV-2 pandemic. Published re- ports have shown that COVID-19 disease presents a high mortality rate in immunocompromised patients, including patients with an active hematologic disease.10,11 This is particularly evident in individuals diagnosed with B-cell NHL treated with immunochemotherapy (ICT) including anti-CD20 monoclonal antibodies (MoAb). In addition, the administration of anti-CD20 MoAb deeply diminishes the seroconversion rate after vaccination.12-15 The aims of our study were to investigate the incidence and severity of SARS-CoV-2 infection and the seroconversion rate in pa- tients diagnosed with FL and MCL who were undergoing maintenance after first-line immunochemotherapy treat- ment based on cyclophosphamide or bendamustine.
In this retrospective analysis, we included all patients di- agnosed with FL and MCL who received upfront RCHOP/ RCVP or BR and sequential RM between March 2020 and March 2022 at six Spanish centers. Patients included in the study had initiated maintenance therapy during the study period or were already on maintenance by March 2020. This study was conducted in accordance with the Decla- ration of Helsinki and approved by the Institutional Clinical Research Ethics Committee of the Vall d’Hebron Institute (study number: PR(AG)179/2022). An inverse probability of treatment weighting (IPTW) average treatment effect analysis was performed according to the type of first-line treatment (bendamustine or cyclophosphamide-contain- ing regimens) to adjust for potential imbalances in other prognostic variables between both groups in binary out- comes (Figure 1B) and SARS-CoV-2 survival (Figure 2B). A standardized mean difference (SMD) with a threshold of 0.10 was used to assess the balance of co-variates between the two groups. COVID-19 disease events were collected from the beginning of RM while COVID-19 disease events before lymphoma onset and during induction therapy were excluded from the analysis. Survival of patients diagnosed with SARS-CoV-2 infection was calculated from the begin- ning of RM until death by SARS-CoV-2 or last follow-up. The severity of SARS-CoV-2 infection was graded accord- ing to the need for either hospitalization or admission to an intensive care unit (ICU). The seroconversion rate was
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