Unexpected toxicity (UT) and opportunistic infections (OI) after rituximab-containing therapy for non-Hodgkin's lymphoma (NHL)

Abstract

e19546 Background: Rituximab (R) is increasingly used for the treatment of B-NHL. Most adverse events are mild to moderate. In rare cases, however, R may be associated with severe UT and OI. Methods: The records of consecutive pts treated at 2 institutions from 01/06 to 12/08 with R-containing chemotherapy or R-maintenance therapy (R-M) for NHL were analyzed for severe UT and OI. UT was considered as related to R if it could not be explained otherwise. Results: 99 pts were included in the cohort study. Pts received a median of 6 cycles (range 1 - 18) of R. A total of 517 cycles of R were evaluable for OI or UT. 7 of 99 pts (7%) (2 females, 5 males) with a median age of 69.5 yrs (range 41–76) experienced UT (n=4) or OI (n=3). UT consisted of interstitial pneumonitis (IP) in 2 pts after 8 and 6 cycles of R-CHOP for diffuse large cell lymphoma (DLCL), a case of congestive heart failure (NYHA III°) after 6x R-CHOP + 2x R-M for follicular lymphoma (FL) and a case of grade 4 pancytopenia lasting for 22 days following 2x R-FC for chronic lymphocytic leukemia. IP completely resolved after initiation of prednisone (n=1) or under empiric antimicrobial therapy (n=1). Congestive heart failure improved under appropriate therapy and the pt received 2 more cycles of R-M. Pancytopenia slowly recovered under therapy with G-CSF, R was terminated. OI consisted of pneumocystis jirovecii pneumonia after 5x R-CHOP-14 for DLCL, Epstein-Barr-virus (EBV)-associated hepatitis after 5x R-CHOP-21 for relapsed FL and generalized herpes zoster following 6x R-bendamustine (RB) + 1x R-M for recurrent BALT-lymphoma. R was restarted in the latter 2 pts. Infections resolved under antimicrobial therapy. EBV-hepatitis improved spontaneously. Moreover, 2 pts were transferred to us for therapy of enterovirus-induced encephalitis after 6x R-CHOP-21 + 2x R-M for FL (n=1) and cerebral toxoplasmosis in a pt heavily pretreated with R-containing therapy for relapsed mantle cell lymphoma (n=1). Conclusions: Severe UT and OI are rare but potentially fatal complications. Awareness of UT/OI, rapid diagnostic proceedings and, whenever possible, initiation of therapy are essential. In selected cases reexposure of R may be feasible. No significant financial relationships to disclose.