Bronchiolitis obliterans with organizing pneumonia after rituximab therapy for non‐Hodgkin's lymphoma

Abstract

Rituximab is a chimeric, anti-CD20 monoclonal antibody initially approved for relapsed, refractory indolent B-cell non-Hodgkin's lymphoma (NHL), and is being applied in an increasing variety of clinical scenarios. Most adverse events are due to an infusion-related symptom complex, and severe pulmonary complications are rare. We describe a case of an NHL patient who received rituximab and developed symptomatic, biopsy-proven multinodular bronchiolitis obliterans with organizing pneumonia (BOOP). This is the first reported case of BOOP associated with single-agent rituximab, and along with two other patients we describe, as well as two prior reports of BOOP in NHL patients receiving rituximab-based combinations, strengthens the possibility of a causal relationship. Moreover, these findings suggest that the incidence of BOOP following rituximab therapy may be higher than has been previously appreciated. Physicians utilizing rituximab should be aware of this association given the difficulty of differentiating between presentations of BOOP and neoplastic pulmonary processes.

Rituximab-induced lung disease: a systematic literature review

“…In six patients, the onset was hyperacute [17][18][19], and, in three patients, it was chronic [16,33,40]. The distributions of tempo of onset and time to onset from the last rituximab infusion showed a nearly perfect match (table 2) and were significantly linked (p,1610 -16 ): the five early-onset cases were hyperacute; 36 out of the 37 delayedonset cases were acute or subacute; and the three late-onset cases were chronic.…”

“…1) [3,, described in anecdotal case reports and in nine case series reporting two cases [16,21,29,34,35], three cases [19,33], four cases [38] or nine cases [39]. A few adequately documented cases occurred during clinical trials.…”

“…The rate of occurrence was 8.4% (nine out of 107) in the Korean case series [39] and 11% (four out of 36) in the Dutch case series [38]. The reason for rituximab therapy was diffuse large B-cell lymphoma in 30 patients, indolent lymphoma in 10 (mantle cell lymphoma (n52) [20,21,39], marginal zone lymphoma or mucosaassociated lymphoid tissue (MALT) (n53) [22,32,33], follicular lymphoma (n54) [24,32,39] and Waldenströ m's macroglobulinaemia (n51) [38]), chronic lymphocytic leukaemia in two [3,37], ITP in two [18,26] and RA in one [16].…”

“…The interval between cycles was 8, 15 or 21 days. Rituximab alone was used in seven patients [20,21,24,26,33,37,40], and with stable-dosage methotrexate for maintenance therapy of RA in one [16]. The other 37 patients received rituximab in combination with multiple chemotherapy regimens (COP, CHOP, CEOP, CVP, ACVBP, VNCOP, fludarabine, cladribine and growth factors (where C is cyclophosphamide, O vinblastine, P prednisone, H doxorubicin, E epirubicin, V etoposide, A Adriamycin, B bleomycin and N mitoxantrone)).…”

“…The second peak, with 29 patients, occurred exactly on day 15, and eight additional cases occurred a few days before (days [8][9][10][11][12][13][14][15] or after (days 15-21) this second peak. Thus 37 patients experienced delayed-onset forms [3,[20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39]. Finally, the third peak reflected late-onset forms, occurring 1-3 months after the last infusion in three patients [16,33,40].…”