At the 2019 American Society of Hematology (ASH) Annual Meeting, Elisabetta Abruzzese, MD, PhD, Hematology S. Eugenio Hospital, Rome, Italy, presented data from the first, large, multi-center trial focusing on treatment of chronic myeloid leukemia (CML) during pregnancy.

Dr Abruzzese spoke with Oncology Learning Network about the history of research pertaining to patients with CML who are pregnant and factors that physicians should consider for patients who are planning to start a family.

What existing data led you and your co-investigators to conduct this research?

Since graduating I have taken interest in CML and lymphomas of adults aged <69 years. In 1990, my mentor, professor Maria Cantonetti, MD, and I began teaming up with obstetrician-gynecologists in order to preserve fertility during treatment and manage pregnancy during illness, particularly in lymphoma patients.

CML patients at this time were facing an overall survival of 4 to 5 years. With the advent of the first targeted therapy in leukemia blocking the protein responsible for the CML—tyrosine kinase inhibitor (TKI)—the whole approach to treating the illness changed very quickly.

With time, profound remissions were no longer rare, but usual, with CML patients looking at life expectancies similar to those in the non-leukemic population. For this reason, a more “normal life” was becoming a reality for younger patients, so we got involved in managing the desire for pregnancy/conception in patients being treated for CML.

We established an Italian national registry (retrospective and prospective) through the GIMEMA (Italian Group for Adult Hematologic Diseases) in 2013. More than 150 cases of conception and pregnancy were collected and included in the registry, the results of which were presented at ASH 2018.

In 2014, a similar registry was established together through European LeukemiaNet (ELN) with a clinician in Russia, Ekaterina Chelysheva, MD, PhD, to expand awareness and knowledge about this subject worldwide. This second registry has seen the participation of 17 countries and has harvested information on >300 pregnancy cases in CML patients.

Our findings suggest that pregnancy in CML is not precluded anymore. With improvement both in the knowledge of different CML drugs and in the outcomes of discontinuation of therapy, it is possible for patients with CML to plan and/or carry a pregnancy to term.

Please briefly describe your study and its findings.

In the study presented at ASH 2019 and the 2019 European Hematology Association (EHA) meeting, we focused on the management of patients with CML during pregnancy with special attention paid to treatment type. We presented data on 224 patients treated for CML at some point during their pregnancy (the majority stopped therapy once pregnancy was discovered).

Of the different drugs available, we confirmed that interferon (an older drug used pre-TKIs to treat CML) can be used at any time during pregnancy. Additionally, certain TKIs with little placental transfer can be used after the 16-week mark, when needed, with a favorable outcome.

Almost 75% of patients studied conceived while receiving TKI treatment. An early interruption in TKI treatment at the point of first positive test prior to organ formation (ie, 4-5 weeks pregnancy) does not seem to be associated with increased congenital abnormalities.

Furthermore, fertility, conception, and delivery for female partners of male patients with CML pose limited concerns, as it seems TKIs have little or no effects on spermatogenesis.

However, female patients should not be exposed to TKIs during pregnancy due to their possible embryotoxicity and teratogenicity. Thus, a pregnant woman with CML should interrupt treatment with TKI during pregnancy.

Leukemic burden should guide the need for restarting/starting therapy. It is important to take into consideration the mother, child, and illness when making clinical decisions.

What do these findings mean for future treatment decisions and research in this setting?

Although CML precluded pregnancy a little more than a decade ago, pregnancy in CML patients is now accepted by most physicians; however, there are no official guidelines available to assist clinicians in making treatment decisions for these patients. 

Some suggestions have been produced since 2009, with recent updates, but all were based on the analysis of case reports and limited personal experience. GIMEMA and ELN are the largest databases collecting information concerning conception, pregnancy, and outcomes.

A position paper should soon be published reviewing all the information already published or presented and suggest some recommendations. Full papers examining different situations in more detail are in preparation.