Table 1.
Studies regarding infectious complications in patients with lymphoma treated with rituximab
| Type of study | Author, year [Ref.] | Patient characteristics | Chemotherapy | Comments | Outcome |
|---|---|---|---|---|---|
| Meta-analysis | Aksoy, 2009 [23] | Lymphoma | Rituximab maintenance therapy | Significantly increased rates of infections and neutropenia. Infection rates were 8.1% in patients who had received rituximab maintenance therapy vs. 3.9% in those who had not. Neutropenia rates were 13.4% vs. 6.3%, respectively (p<0.001) | Meta-analysis of the RCTs demonstrated that rituximab maintenance therapy significantly increased the RR of both infection and neutropenia in patients with lymphoma |
| Meta-analysis of RCTs | Vidal, 2009 [28] | Follicular lymphoma | Rituximab | Patients undergoing rituximab maintenance therapy had more infection-related adverse events than patients in the observation arm (RR 1.99, 95% CI 1.21–3.27). When only grade 3 or 4 infection-related adverse events were included in the analysis, this effect was even more pronounced (RR 2.90, 95% CI 1.24–6.76) | |
| RCT phase II | Eve, 2009 [29] | Previously untreated mantle cell lymphoma | Fludarabine and cyclophosphamide with or without rituximab | Non-hematological toxicity was similar between the two treatment arms | |
| RCT | Kaplan, 2005 [30] | NHL (HIV patients) | R-CHOP vs. CHOP | 99 patients treated with R-CHOP vs. 51 patients treated with CHOP (infection rate NR). Presence of opportunistic infections in the R-CHOP group and absence of these infections in the CHOP group | Infection-related death was 14% with R-CHOP vs. 2% with CHOP (p = 0.035) |
| RCT | Lenz, 2005 [31] | NHL Mantle cell | R-CHOP vs. CHOP | 33% (grade I–II) and 5% (grade III/IV) of 62 patients treated with R-CHOP developed infections vs. 29% (grade I–II) and 6% (grade III/IV) of 60 patients treated with CHOP | NR |
| RCT | Hiddemann, 2005 [32] | NHL follicular | R-CHOP vs. CHOP | 5% of 223 patients treated with R-CHOP developed infections vs. 7% of 205 patients treated with CHOP | Infection-related death 1.9% with R-CHOP vs. 0.5% with CHOP |
| RCT | Feugier, 2005 [33], Coiffier, 2002 [34] | DLBCL | R-CHOP vs. CHOP | 65% (any grade) and 12% (grade III/IV) of 202 patients treated with R-CHOP developed infections vs. 65% (any grade) and 20% (grade III/IV) of 197 patients treated with CHOP | Infection-related death 1.7% with R-CHOP vs. 1.9% with CHOP |
| RCT | Habermann, 2006 [35] | DLBCL | R-CHOP vs. CHOP | 17% of 318 patients treated with R-CHOP developed infections vs. 16% of 314 patients treated with CHOP | |
| RCT | Pfreundschuh, 2006 [36] | NHL B-cell | R-CHOP vs. CHOP | 7% of 411 patients treated with R-CHOP developed infections vs. 8% of 413 patients treated with CHOP | |
| RCT | Forstpointner, 2004 [37] | NHL follicular and mantle cell | Rituximab + FCM vs. FCM | 1.5% (grade III/IV) of 62 patients treated with R-FCM developed infections vs. 1.5% (grade III/IV) of 66 patients treated with FCM | |
| RCT | Marcus, 2005 [38] | NHL follicular | Rituximab + CVP vs. CVP | No difference between the two groups (162 patients in R-CVP vs. 159 in CVP) | |
| RCT | Herold, 2003 [39] | Indolent NHL | Rituximab + MCP vs. MCP | No difference in infection rates between the two groups (55 patients in R-MCP vs. 51 in MCP) | |
| Controlled clinical trial | Dungarwalla, 2008 [40] | 14 heavily pre-treated CLL patients | HDMP ± rituximab | 2 cases of systemic candidiasis, 2 cases of aspergillosis, 1 case of VZV, 1 case of adenovirus, bacteremia. Although HDMP-R causes little or no myelosuppression, the addition of rituximab might have predisposed to opportunistic infections. However, heavily pre-treated CLL patients have an increased susceptibility to infection intrinsic to the disease. Small series of patients/caution about conclusions | All patients died (except for the case with VZV) |
| RCT phase II | Del Poeta, 2008 [41] | B-CLL | Fludarabine and rituximab | 3 dermatomal herpes zoster infections and 4 localized herpes simplex infections | |
| Retrospective study | Ennishi, 2008 [42] | 64 yo M with follicular lymphoma stage IVa (partial response to treatment); 61 yo M with diffuse large B-cell lymphoma stage 1a (complete response to treatment) | R-CHOP | 13 of 90 (14%) patients developed interstitial pneumonitis during R-CHOP therapy, compared with none of 105 patients treated with CHOP alone; 2 of these cases were PCP | All patients responded well to treatment, and recovered within 2–3 weeks |
| Retrospective study | Lee, 2008 [19] | 46 patients with relapsed indolent or high-risk aggressive B cell NHL who received rituximab (17 patients) or not (29 patients) before autologous HSCT | Rituximab | Post-transplant infectious complications up to 6 months after transplantation. Seventeen of 46 patients received rituximab before HSCT. Three of them suffered from CMV infection and two of them developed CMV disease. All of the patients with CMV disease recovered after ganciclovir and CMV-specific immunoglobulin therapy. Twenty-nine of 46 patients without rituximab treatment before HSCT did not develop CMV after HSCT. Risk of CMV infection after autologous HSCT higher in rituximab-treated patients (17.6% vs. 0%, p = 0.045). Risk of CMV disease had higher trend with rituximab therapy than without rituximab therapy (11.7% vs. 0%, p = 0.131) | All 3 cases responded to ganciclovir combined with CMV-specific immunoglobulin |
| RCT phase III | Van Oers, 2006 [43] | Relapsed/resistant follicular lymphoma | R-CHOP | Upper respiratory tract infections mostly | |
| RCT phase III | Ghielmini, 2005 [44] | Mantle cell lymphoma | R-CHOP | One patient experienced three episodes of pneumonia, 1 case of hepatitis, 1 case of septic shock | |
| RCT phase II | Hainsworth, 2003 [45] | CLL/SL | Staphylococcus aureus pneumonia, 1 patient; localized herpes zoster, 1 patient; and gastroenteritis, probably viral, 1 patient |
CHOP, cyclophosphamide, doxorubicin, vincristine, and prednisone; CLL, chronic lymphocytic leukemia; CVP, cyclophosphamide, vincristine, and prednisone; CMV, cytomegalovirus; DLBCL, diffuse large B-cell lymphoma; FCM, fludarabine, cyclophosphamide, and mitoxantrone; HDMP, high-dose methylprednisolone; HIV, human immunodeficiency virus; HSCT, hematological stem cell transplantation; M, male; MCP, mitoxantrone, chlorambucil, and prednisolone; NHL, non-Hodgkin lymphoma; NR, not reported; PCP, Pneumocystis jiroveci (carinii) pneumonia; R, rituximab; RCT, randomized controlled trial; RR, relative risk; SL, small lymphocytic lymphoma; VZV, varicella zoster virus; yo, year-old.