25 Year Old Female Conceiving 6 Months After Last Dose of Rituximab: a Case Report

Abstract 4924

For female patients treated with rituximab, a monoclonal anti-CD20 antibody, it is recommended to wait 12 months post-treatment before pregnancy to avoid fetal B cell depletion. We report a case of a 25 year old female with a history of Grade II follicular lymphoma, Stage III who was treated with CHOP/R and maintenance rituximab therapy which was stopped when she expressed intentions for pregnancy. However, she conceives within only 6 months after her last dose of rituximab. This prompts questions of risks to the fetus.

Rituximab is a monoclonal anti-CD20 antibody which targets and destroys normal and malignant CD20 positive B cells. As an IgG molecule, rituximab can cross the placenta, and has been documented to cause B cell depletion and immunosuppression in the fetus (McKeever et al, 2003). During treatment, high drug levels are detectable in the umbilical cord blood, and remains in the patient's blood between 3–6 months post-treatment (Pereg et al, 2007). The half life of rituximab varies with tumour burden and ranges from 3 – 19 days. B cell levels start to recover at 6 months post-treatment and are normal by 12 months. Hence, it is recommended by the manufacturer that pregnancies should be separated from rituximab use by a minimum of 12 months.

Current literature regarding rituximab's safety in pregnancy is limited to animal studies and 10 case reports. When pregnant macaque cynomolgus females were exposed in 1^st trimester, no teratogenic or embryotoxic effects were shown. There was a decrease in B cell levels but these were reversible by 179 days (McKeever et al., 2003).

Among case reports, six involved women treated for hematological conditions. Of these cases, one was inadvertently exposed in 1^st trimester and the fetus had B cell depletion that recovered to normal levels by 16 days (Kimby, 2004). All other cases were exposed in 2^nd trimester of which two had transient B cell depletion that recovered by 4 months. All babies were healthy at birth, had normal antibody titres after their first vaccinations and normal childhood development at follow-up (Friedrich, 2006; Decker 2006). Four case reports involved rituximab use for non-hematological conditions; two cases of 1^st trimester and two cases of 3^rd trimester exposure. Only one 3^rd trimester case reported transient fetal B cell depletion that recovered by 6 months (Klink, 2008). Again, all babies were healthy at birth and at follow-up, including normal antibody titres after vaccinations.

From the cases reported, regardless of trimester exposure, the B cell depletion effect was only transient with no documented short-term or long-term effects on the baby's immune function and overall development. In this case, the patient stopped rituximab therapy 6 months prior to conception. There were no complications during pregnancy or delivery. Furthermore, a healthy baby boy was born at 42 weeks gestation with normal apgar scores, length at 75th percentile, and normal weight of 8 lbs 16 oz. Since the baby was clinically stable after delivery, B cell levels were not drawn. At 3 months old, the baby was healthy and had no difficulties with vaccinations to date. This is yet another case to add to the small literature base, and we hope it can help further inform the usage of rituximab during pregnancy.