Page 164 - Haematologica Vol. 107 - September 2022

ARTICLE - Non-Hodgkin Lymphoma
Humoral immune depression following autologous stem cell transplantation is a marker of prolonged response duration in patients with mantle cell lymphoma
Louise Bouard,1 Benoit Tessoulin,2 Catherine Thieblemont,3 Kamal Bouabdallah,4 Thomas Gastinne,1 Lucie Oberic,5 Sylvain Carras,6 Caroline Delette,7 Olivier Casasnovas,8 Caroline Dartigeas,9 Victoria Cacheux,10 Sibylle Masse,11 Olivier Hermine12 and Steven Le Gouill2,13
1Department of Hematology, CHU Nantes, Nantes; 2Department of Hematology CHU Nantes, INSERM CRCINA Nantes-Angers, and NeXT, Nantes University, Nantes; 3Department of Hematology, Saint-Louis Hospital, AP-HP, Paris 7 University, Paris; 4Department of Hematology, CHU Bordeaux, Bordeaux; 5Department of Hematology, IUC Toulouse Oncopole, Toulouse; 6Department of Hematology, CHU Grenoble, Grenoble; 7Department of Hematology, CHU Amiens, Amiens; 8Department of Hematology, CHU Dijon Bourgogne, INSERM 1231, Dijon; 9Department of Hematology, CHU Tours, Tours; 10Department of Hematology, CHU Clermont-Ferrand, Clermont-Ferrand; 11Lysarc Institut Carnot CALYM, Lyon-Sud Hospital, Lyon; 12Necker University Hospital, Paris and 13Institut Curie, Paris France.
Abstract
Rituximab maintenance (RM) after autologous stem cell transplantation (ASCT) is standard-of-care for young patients with mantle cell lymphoma (MCL). RM may enhance post-transplantation immune depression and risk of infections. We compared infection incidence and immune consequences of RM versus observation in transplanted MCL patients. All randomized patients included in the LyMa trial were eligible. The following parameters were collected prospectively: occurrence of fever, infection, hospitalization, neutropenia, hypogammaglobulinemia, CD4 lymphopenia and γ globulin (Ig) substitution. The post-ASCT period was divided into four periods in order to assess the possible effects of RM or ASCT on immune status. Each arm included 120 patients. Concerning infection incidence and all biological parameters, there was no difference between the two arms during the first year post ASCT. After this period, RM patients were more exposed to fever (P=0.03), infections (P=0.001), hypogammaglobulinemia (P=0.0001) and Ig substitution (P<0.0001). Incidences of hospitalization, neutropenia and CD4 lymphopenia were not different between the two arms. The number of rituximab injections was correlated with infections and hypogammaglobulinemia, P<0.0001 and P=0.001; but was not correlated with neutropenia and CD4 lymphopenia. Ig substitution did not modify infection incidence. Patients who presented hypogammaglobulinemia <6 g/L or <4 g/L had longer 3-years progression-free survival (PFS), this applies to RM patients (P=0.012 and P=0.03) and to the global cohort (P=0.008 and P=0.003). Hypogammaglobulinemia did not influence overall survival. Occurrence of infectious event, neutropenia and CD4 lymphopenia did neither influence PFS nor overall survival. Post-ASCT RM in MCL patients causes sustained hypogammaglobulinemia, which is independently correlated with improved PFS.
Correspondence: S. Le Gouill steven.legouill@curie.fr
Received: Accepted: Prepublished:
July 8, 2021. February 10, 2022. February 17, 2022.
https://doi.org/10.3324/haematol.2021.279561
©2022 Ferrata Storti Foundation Published under a CC BY-NC license
Introduction
Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lym- phoma (NHL) which accounts for approximately 6% of NHL among adults.1 Standard-of-care for young and fit pa- tients consists in induction with high-dose cytarabine plus rituximab containing chemotherapy, followed by autologous stem cell transplantation (ASCT).2 It has been demonstrated that a 3-year rituximab maintenance (RM) with one injection every 2 months following ASCT im-
proved event-free, progression-free and overall survivals (EFS, PFS and OS respectively)3.
Rituximab is a chimeric IgG1 monoclonal antibody target- ing CD20, with high efficiency in patients with B-cell lym- phomas.4 Data on infectious toxicity caused by RM in MCL are sparse, and sometimes collected from heterogeneous or retrospective cohorts which contain different types of B-cell disorders, chemotherapy associations and treat- ment schedules.5 For patients with follicular lymphoma receiving RM, prospective studies reported an increased
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