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Maintenance therapy with ex vivo expanded lymphokine‐activated killer cells and rituximab in patients with follicular lymphoma is safe and may delay disease progression
Author(s) -
LópezDíaz de Cerio Ascensión,
GarcíaMuñoz Ricardo,
Pena Esther,
Panizo Ángel,
Feliu Jesús,
Giraldo Pilar,
RodríguezCalvillo Mercedes,
MartínezCalle Nicolás,
Grande Carlos,
Olave María T.,
AndradeCampos Marcio,
Bandrés Eva,
NúñezCórdoba Jorge M.,
Inogés Susana,
Panizo Carlos
Publication year - 2020
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.16474
Subject(s) - antibody dependent cell mediated cytotoxicity , medicine , rituximab , ex vivo , follicular lymphoma , immunology , peripheral blood mononuclear cell , lymphokine activated killer cell , cd20 , chronic lymphocytic leukemia , monoclonal antibody , lymphoma , leukemia , antibody , in vivo , immune system , t cell , biology , interleukin 21 , in vitro , biochemistry , microbiology and biotechnology
Summary Anti‐cluster of differentiation 20 (CD20) monoclonal antibodies (mAbs) have shown promise in follicular lymphoma (FL) as post‐induction therapy, by enhancing antibody‐dependent cellular cytotoxicity (ADCC). However, cytotoxic cells are reduced after this treatment. We hypothesised that ex vivo expanded lymphokine‐activated killer (LAK) cells administered to FL‐remission patients are safe and improve anti‐CD20 efficacy. This open, prospective, phase II, single‐arm study assessed safety and efficacy of ex vivo expanded LAK cells in 20 FL‐remission patients following rituximab maintenance. Mononuclear cells were obtained in odd rituximab cycles and stimulated with interleukin 2 (IL‐2) for 8 weeks, after which >5 × 10 8 LAK cells were injected. Patients were followed‐up for 5 years. At the end of maintenance, peripheral blood cells phenotype had not changed markedly. Natural killer, LAK and ADCC activities of mononuclear cells increased significantly after recombinant human IL‐2 (rhIL‐2) stimulation in all cycles. Rituximab significantly enhanced cytotoxic activity. No patients discontinued treatment. There were no treatment‐related serious adverse events. Three patients had progressed by the end of follow‐up. After a median (interquartile range) follow‐up of 59.4 (43.8–70.9) months, 85% of patients remained progression free. No deaths occurred. Quality‐of‐life improved throughout the study. Post‐induction LAK cells with rituximab seem safe in the long term. Larger studies are warranted to confirm efficacy.