Diagnosis of cancer during pregnancy is emotionally stressful for the patient and her family and presents challenges for the medical team including how to best minimize risk of adverse fetal events while still ensuring the best disease outcome for the woman. Cancer is diagnosed during 0.1% of pregnancies with lymphoma being the 4th most common cancer effecting 1 in 6000 pregnancies (Brenner, B et al, The Lancet, 2012 & Pereg, D et al, Haematologica, 2007). This prevalence is anticipated to grow given the shift towards increasing average age at time of pregnancy. The overall rarity of this presentation and the variance of the histological diagnoses have prevented the conduction of large prospective clinical trials, and thus no stringent management algorithms exist.
From 2005 women with a diagnosis of lymphoma during pregnancy were consented and enrolled into this IRB-approved prospective database trial. Patients received multidisciplinary care including counseling and co-management with our maternal-fetal medicine and reproductive medicine collaborators.
A total of 19 patients (pts) were consented with full treatment (tx) and fetal outcome data available for 16. The median age of the women was 30 (20–38) years with a slightly lower median age for the classical Hodgkin lymphoma (HL) pts of 28.5 (20–35) years. Ten pts had HL (6 early stage [ES], 2 advanced stage [AS], 2 relapsed), while the remaining 9 had NHL (3 [2 ES, 1 AS] diffuse large B-cell lymphoma [DLBCL], 1 ES anaplastic lymphoma kinase [ALK]-positive LBCL, 1 primary CNS DLBCL, 1 AS follicular lymphoma [FL] with transformation to DLBCL, 1 ES FL, 1 AS MALT, and 1 ALK+ anaplastic LCL).
Fifteen pts had diagnoses made of initial or relapsed disease during pregnancy at a median of 18 (3–34) weeks (wks) gestation with 33% during 1st trimester, 54% during 2nd trimester, and 13% during 3rd trimester. Four pts with chronic oligomenorrhea with baseline negative serum pregnancy tests became pregnant while on tx (ABVD, rituximab plus gemcitabine, R-CHOP, and maintenance rituximab) with fetal loss in all 4 with spontaneous abortions from wk 8 to 26 and an elective abortion at wk 6.
Four pts of the 15 pts deferred start of tx until after delivery (ES HL and ES primary mediastinal DLBCL pts, a relapsed HL pt, and a ES FL grade 3B pt diagnosed respectively at wks gestation of 31, 34, 14, and 27) and the 3 pts for whom outcome data is available have durable complete remissions (CRs) at a median of 25 (5–52) months (mos) of follow-up with babies born at a median of 35 (31–37) wks at a median birth weight of 2381 (1814–3004) grams with 75% being above the 50% weight percentile. Ten pts started tx while pregnant (80% during 2nd/3rd trimester) at a median of 18 (11–29) wks (ABVD/AVD in 5, R-CHOP/AVD in 1, R-CHOP in 2, HCVAD in 1, and DeAngelis regimen in 1) with all but 1 pt having MRIs and ultrasounds for staging. Seven of these pts delivered babies at a median of 37 (33–39) weeks with 57% delivered at term, a median birth weight of 2948 (2494–3061) grams with 50% being above the 50% weight percentile, and no fetal malformations. At a median of 20.5 (8–53) mos of follow-up 60% of the pts who received tx while pregnant are free of progression while 2 HL pts (1 ES HL pt 22 months after delivery) died from disease progression and 2 pts are on active treatment for relapsed disease (HL and ALK+ LBCL). Three pts experienced fetal loss including a AS HL pt with SVC syndrome necessitating intubation with prolonged ICU care (spontaneous abortion at 23 wks), a AS HL pt who started ABVD at 14 wks of gestation (stillbirth of twins at 26 wks), and the pt with CNS DLBCL who initiated the DeAngelis regimen with high dose methotrexate at 13 wks (elective abortion at 19 wks).
Given the rarity of the diagnosis of lymphoma during pregnancy our series to our knowledge represents one of the largest single center prospective clinical studies. Our data highlight that ABVD, R-CHOP, and HCVAD can be given with excellent outcomes for pt and fetus at a preferred start of 2nd trimester or later, although 1 pt with symptomatic HL did start ABVD early at 11 wks of gestation with preservation of positive outcomes. These findings also emphasize the importance of co-management through all the steps of treatment with a maternal-fetal medicine colleague. Furthermore, we show the need to counsel oligomenorrheic pts on the risk of still becoming pregnant and perform assessments to rule-out pregnancy beyond the baseline pre-tx visit.
Fanale:Millennium: Research Funding; MedImmune: Research Funding; Novartis: Honoraria, Research Funding, Travel Expenses, Travel Expenses Other; Genentech: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Travel Expenses, Travel Expenses Other; Seattle Genetics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Travel Expenses Other; Onyx: Research Funding; Allos: Membership on an entity's Board of Directors or advisory committees. Lai:Celgene: Membership on an entity's Board of Directors or advisory committees. Younes:Seattle Genetics, Inc.: Consultancy, Research Funding; Millennium: Honoraria; Novartis: Honoraria, Research Funding; Celgene: Honoraria; Affimed: Research Funding; Gilead: Research Funding; Johnson & Johnson: Research Funding.
Asterisk with author names denotes non-ASH members.