Advertisement

Implication of Rituximab Infusion Reactions on Clinical Outcomes in Patients With Diffuse Large B-cell Lymphoma: A Single Institution Experience

Published:September 30, 2019DOI:https://doi.org/10.1016/j.clml.2019.09.604

      Abstract

      Background

      The addition of the anti-CD20 monoclonal antibody rituximab to chemotherapy for diffuse large B-cell lymphoma (DLBCL) has led to improvements in progression-free survival and overall survival, although the exact mechanism of rituximab is not known. Rituximab administration often results in transient, non–life-threatening infusion reactions (IRs). We report a retrospective cohort of patients with DLBCL who received rituximab to determine the significance of IRs on clinical outcomes.

      Patients and Methods

      We identified and analyzed a retrospective cohort of 229 patients with DLBCL. They were stratified into 2 cohorts; those who did and did not have an IR. Univariate and multivariate analyses were performed to evaluate the prognostic significance of rituximab-related IRs relative to DLBCL subtype, International Prognostic Index score, c-Myc translocations or amplifications, chemotherapy regimen, and Ki-67 proliferative index.

      Results

      Baseline characteristics did not differ significantly between the 2 groups. Rituximab was included as initial treatment in all patients. Patients with an IR had a significantly higher overall survival (hazard ratio, 0.26; 95% confidence interval, 0.07-0.95) at 5 years. In addition, subgroup analysis showed a significantly higher progression-free survival in patients with the germinal center subtype of disease and c-Myc alterations who had a rituximab-related IR (log-rank P < .0001).

      Conclusions

      The presence of a rituximab-related IR is associated with a better overall survival in patients with DLBCL. Although limited by the small sample size and retrospective nature, these results provide rationale for further investigation into the mechanism of action of rituximab in order to optimize the efficacy of CD20 monoclonal antibodies.

      Keywords

      To read this article in full you will need to make a payment

      Subscribe:

      Subscribe to Clinical Lymphoma, Myeloma and Leukemia
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Dotan E.
        • Aggarwal C.
        • Smith M.R.
        Impact of rituximab (Rituxan) on the treatment of B-cell non-Hodgkin’s lymphoma.
        P T. 2010; 35: 148-157
        • Salles G.
        • Barrett M.
        • Foa R.
        • et al.
        Rituximab in B-cell hematologic malignancies: a review of 20 years of clinical experience.
        Adv Ther. 2017; 34: 2232-2273
        • Vose J.M.
        • Link B.K.
        • Grossbard M.L.
        • et al.
        Phase II study of rituximab in combination with CHOP chemotherapy in patients with previously untreated, aggressive non-Hodgkin’s lymphoma.
        J Clin Oncol. 2001; 19: 389-397
        • Coiffier B.
        • Lepage E.
        • Briere J.
        • et al.
        CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large B-cell lymphoma.
        N Engl J Med. 2002; 346: 235-242
        • Habermann T.M.
        • Weller E.A.
        • Morrison V.A.
        • et al.
        Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma.
        J Clin Oncol. 2006; 24: 3121-3127
        • Bauer K.
        • Rancea M.
        • Roloff V.
        • et al.
        Rituximab, ofatumumab, and other monoclonal anti-CD20 antibodies for chronic lymphocytic leukaemia.
        Cochrane Database Syst Rev. 2012; 11: CD008079
        • Tobinai K.
        • Klein C.
        • Oya N.
        • Fingerie-Rowson G.
        A review of obinutuzumab (GA101), a novel type II anti-CD20 monoclonal antibody, for the treatment of patients with B-cell malignancies.
        Adv Ther. 2017; 34: 324-356
        • Alduaij W.
        • Illidge T.
        The future of anti-CD20 monoclonal antibodies: are we making progress?.
        Blood. 2011; 117: 2993-3001
        • Maloney D.G.
        • Smith B.
        • Rose A.
        Rituximab: mechanism of action and resistance.
        Semin Oncol. 2002; 29: 2-9
        • Boross P.
        • Leusen J.H.W.
        Mechanisms of action of CD20 antibodies.
        Am J Cancer Res. 2012; 2: 676-690
        • Weiner G.J.
        Rituximab: mechanism of action.
        Semin Hematol. 2010; 47: 115-123
        • Uchida J.
        • Hamaguchi Y.
        • Oliver J.A.
        • et al.
        The innate mononuclear phagocyte network depletes B lymphocytes through Fc receptor-dependent mechanisms during anti-CD20 antibody immunotherapy.
        J Exp Med. 2004; 199: 1659-1669
        • Di Gaetano N.
        • Cittera E.
        • Nota R.
        • et al.
        Complement activation determines the therapeutic activity of rituximab in vivo.
        J Immunol. 2003; 171: 1581-1587
        • Klepfish A.
        • Rachmilewitz E.A.
        • Kotsianidis I.
        • Patchenko P.
        • Schattner A.
        Adding fresh frozen plasma to rituximab for the treatment of patients with refractory advanced CLL.
        QJM. 2008; 101: 737-740
        • Klepfish A.
        • Gilles L.
        • Ioannis K.
        • Rachmilewitz E.A.
        • Schattner A.
        Enhancing the action of rituximab in chronic lymphocytic leukemia by adding fresh frozen plasma: complement/rituximab interactions & clinical results in refractory CLL.
        Ann N Y Acad Sci. 2009; 1173: 867-873
        • Weng W.K.
        • Levy R.
        Two immunoglobulin G fragment C receptor polymorphisms independently predict response to rituximab in patients with follicular lymphoma.
        J Clin Oncol. 2003; 21: 3940-3947
        • Wang S.Y.
        • Racila E.
        • Taylor R.P.
        • Weiner G.J.
        NK-cell activation and antibody-dependent cellular cytotoxicity induced by rituximab-coated target cells is inhibited by the C3b component of complement.
        Blood. 2008; 111: 1456-1463
        • van der Kolk L.E.
        • Grillo-Lopez A.J.
        • Baars J.W.
        • Hack C.E.
        • van Oers M.H.
        Complement activation plays a key role in the side-effects of rituximab treatment.
        Br J Haematol. 2001; 115: 807-811
        • International Non-Hodgkin’s Lymphoma Prognostic Factors Project
        A predictive model for aggressive non-Hodgkin’s lymphoma.
        N Engl J Med. 1993; 30: 987-994
        • Hans C.P.
        • Weisenburger D.D.
        • Greiner T.C.
        • et al.
        Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray.
        Blood. 2004; 103: 275-282
        • Cabanillas F.
        • Shah B.
        Advances in diagnosis and management of diffuse large B-cell lymphoma.
        Clin Lymphoma Myeloma Leuk. 2017; 17: 783-796
        • Petrich A.M.
        • Nabhan C.
        • Smith S.M.
        Myc-associated and double-hit lymphomas: a review of pathobiology, prognosis, and therapeutic approaches.
        Cancer. 2014; 120: 3884-3895
        • Quesada A.E.
        • Medeiros L.J.
        • Desai P.A.
        • et al.
        Increased MYC copy number is an independent prognostic factor in patients with diffuse large B-cell lymphoma.
        Mod Pathol. 2017; 30: 1688-1697
        • Zhou K.
        • Xu D.
        • Cao Y.
        • Wang J.
        • Yang Y.
        • Huang M.
        C-MYC aberrations as prognostic factors in diffuse large B-cell lymphoma: a meta-analysis of epidemiological studies.
        PLoS One. 2014; 9: 1-9
        • Perry A.M.
        • Alvarado-Bernal Y.
        • Laurini J.A.
        • et al.
        MYC and BCL2 protein expression predicts survival in patients with diffuse large B-cell lymphoma treated with rituximab.
        Br J Haematol. 2014; 165: 382-391
        • Nowakowski G.S.
        • Czuczman M.S.
        ABC, BCB, and double-hit diffuse large B-cell lymphoma: does subtype make a difference in therapy selection?.
        Am Soc Clin Oncol Educ Book. 2015; : e449-e457
        • Sopp J.
        • Cragg S.
        Deleting malignant B cells with second-generation anti-CD20 antibodies.
        J Clin Oncol. 2018; 22: 2323-2325