P714: EFFECT OF TYROSINE KINASE INHIBITORS ON MALE FERTILITY IN PATIENTS WITH CHRONIC PHASE CHRONIC MYELOID LEUKAEMIA

Abstract

Background: With the current availability of 3+ generations of tyrosine kinase inhibitors (TKIs) and the resultant survival benefit, chronic phase chronic myeloid leukaemia (CP-CML) is considered a chronic disease for most patients. Consequently, haematologists are faced more with questions regarding the effects of treatment on fertility and pregnancy outcomes. Whilst the teratogenic effect of TKIs is well established, data on their effect on fertility, and especially male fertility, are scarce. Semen analysis parameters (sperm number, motility and morphology) remain the cornerstone in assessing male fertility, despite its limitations in comprehensively assessing sperm functions. Aims: To compare semen analysis parameters before and after TKI therapy in CP-CML patients treated in the haematology department of Imperial College Healthcare NHS Trust (ICHNT). Methods: In collaboration with the Andrology Department, newly diagnosed men with CP-CML are offered sperm banking before starting cytoreductive or TKI therapy, and sperm analyses are routinely undertaken. Patients treated with TKIs who had sperm banking at diagnosis were invited for repeat semen analysis. Treatment history and semen analysis parameters were collected from patients’ paper/electronic medical records. Median and range were used to summarize continuous non-parametric data. Paired sample t-test was used to compare continuous semen analysis parameters before and after TKI therapy. Double-sided p value of < 0.05 was considered as statistically significant. SPSS version 25 software was used for statistical analysis. Results: Twenty-five patients were identified to have a semen analysis performed around the time of starting TKI therapy and were approached for repeat testing. Of those, 13 refused to participate, 1 was an international patient no longer residing in the UK and 1 stopped TKI therapy for treatment free remission trial. Therefore, 10 patients were finally included. Median age at diagnosis was 35.6 years (range: 22.9-45.4) and patients were diagnosed between 2001 to 2014. Six and 2 patients received hydroxyurea and interferon α, respectively, before TKI therapy. Six patients received 1 TKI (imatinib (IM), n = 4; nilotinib (NIL), n = 1; bosutinib (BOS), n = 1), 2 received 2 TKIs (IM followed by NIL), and 2 received 3 TKIs (IM, DAS, NIL and IM, NIL, DAS). Switches were for failure and/or intolerance. Median duration of TKI therapy at the time of repeat semen analysis was 5.9 years (range: 3.3-16.5). Patients 6 and 10 had the initial semen analysis after 736 and 475 days, respectively, from commencing TKI therapy and all remaining patients had it before starting. All patients had a deep molecular response at the time of the repeat semen analysis. The differences between sperm concentration, % progressive motility and % total motility were all non-statistically significant (p = 0.457, 0.535, and 0.574, respectively). In 2 patients the semen parameters were below the reference ranges in both occasions. Morphology (% normal forms) was less than the reference 4% in the repeat samples of 5 patients (Table 1). Image:Summary/Conclusion: In our cohort, no significant differences were found in sperm concentration or motility before and after treatment with different TKIs for a prolonged period. The relevance of the finding of a low % of normal forms, in the presence of normal sperm concentration and motility, in some of the patients in the semen sample after TKI therapy is not clear. Studies with larger sample size would be needed to confirm or refute our findings.