Lymphoma in Pregnancy

By Rebecca Elstrom, MD

Although rare, cancer, including lymphoma, does occur in pregnant women. The effect of both the cancer and treatment on the fetus is a major concern to expectant parents, adding to the stress of dealing with a diagnosis of malignancy. Some types of anti-cancer treatment, such as the anti-folate drug methotrexate, are best avoided at all stages of fetal development, and the effects of other classes are likely dependent in part on the physical characteristics of each drug, which can affect the ability of each to cross the placenta. For example, certain anthracyclines, which are critical in the treatment of lymphoma and other hematologic malignancies, cross the placenta poorly, whereas others, such as idarubicin and liposomal formulations of doxorubicin, have physical characteristics which allow greater penetration into the fetal circulation.

Fortunately, evidence is mounting that exposure of the fetus to many common types of chemotherapy after the first trimester does not produce negative effects on normal development, either in terms of organ development or neurologic function. A recent study published in the Lancet Oncology observed children born to mothers that were treated for cancer and compared their physical, behavioral and cognitive development to established norms in similar populations. The authors found that children born to mothers that were exposed to chemotherapy for treatment of cancer after the first trimester did not show notable differences in development from children in the general population matched for other characteristics. Although the numbers were too small to compare different chemotherapy regimens in their effects, the general finding of no significant decrement in development in this prospective study was encouraging. Of note, the most powerful predictor of cognitive developmental delay was premature birth, comparable to that seen in children born prematurely for other reasons. Although it is not possible to definitively rule out an additional effect of chemotherapy in this group, this finding argues that “iatrogenic prematurity,” or delivery of a baby before term for purposes of treating the mother’s cancer, is likely to be counter-productive, unless undertaken for a specific reason other than sparing the fetus exposure to chemotherapy.

Another critically important question involves the outcome of treatment for the patient. Pregnancy affects blood volume and could affect the body’s handling and metabolism of chemotherapy drugs. No large prospective studies are available to address this issue, but a presentation by Dr. Andrew Evens of the University of Massachusetts at the most recent meeting of the American Society of Hematology in December of 2011 showed excellent outcomes in a retrospective study of 88 women diagnosed with lymphoma during pregnancy. Weill Cornell Medical College participated in the study. Although the retrospective nature of the study and heterogeneity of the patients preclude definitive conclusions, this study provides more encouraging data for women facing a diagnosis of lymphoma during pregnancy. Click here to read the abstract.

ASH Conference: Radioimmunotherapy as Part of First Line Therapy for Low Grade Lymphoma

By Rebecca Elstrom, MD

Update: this study is closed to enrollment. 

Radioimmunotherapy (RIT), or radiation targeted to lymphoma cells through conjugation to a monoclonal antibody, has long been known to be effective therapy in patients with relapsed indolent non-Hodgkin’s lymphomas.  Its use as first line therapy has been limited, however. This weekend at the American Society of Hematology (ASH) meeting, several studies exploring the use of RIT in initial therapy of low grade lymphomas, either alone or following chemotherapy, were reported.

Two studies explored the use of 90Y-ibritumomab tiuxetan (Zevalin) alone;  one presented by Dr. Pica of Genova on behalf of an Italian cooperative group exploring a single dose, and one presented by Dr. Illidge from the University of Manchester with fractionated dosing (multiple doses of the RIT, in this case 2). Both studies showed high response rates with this brief and simple strategy, and durations of remission comparable to front line chemotherapy with no excessive toxicity.

Two other studies explored the use of RIT as consolidation following initial chemotherapy. The first, presented by Dr. Press of the University of Washington, was a large multicenter study comparing Rituximab plus CHOP chemotherapy (R-CHOP) to CHOP followed by 131I-tositumomab (Bexxar). There was no difference between the two groups in response rate or duration of response. A caveat to this study is the fact that, at the time it was designed, there was concern that giving the anti-CD20 antibody rituximab prior to RIT would inhibit radiation dose delivery, as 131I-tositumomab also requires binding to CD20 in order to deliver the radiation dose to lymphoma cells. This concern does have support in laboratory studies, but it has become clear in the years since this study was designed that anti-CD20 antibody therapy with rituximab is a critical contributor to response and survival in follicular lymphoma. The second study of chemotherapy followed by RIT was presented by Dr. Fowler of MD Anderson Cancer Center. This group evaluated an induction chemotherapy regimen containing rituximab, fludarabine, mitoxantrone and dexamethasone (R-FND) followed by 90Y-ibritumomab tiuxetan. This study showed high response rates and long time to progression, but toxicity of the regimen was of some concern, possibly due to the fact that fludarabine has significant bone marrow suppressive effects, which is also the main side effect of RIT.

Overall, these presentations confirmed the impressive activity of RIT in low grade lymphoma, and extended the experience using RIT as part of first line therapy, demonstrating feasibility, safety and efficacy of this simple and very well tolerated therapeutic approach.

At Weill Cornell Medical College we are exploring radioimmunotherapy as first treatment of follicular lymphoma using a combined strategy of non-radiation tagged antibody to CD20 in combination with radio-labeled antibody against an alternative protein, CD22. This study is designed to maximize the benefit of anti-CD20 directed therapy in addition to radiation dose delivery by targeting the radio-labeled antibody to an alternative target. Click here to read more about this study.