Session: 632. Chronic Myeloid Leukemia: Therapy: Poster III
Hematology Disease Topics & Pathways:
Biological, Diseases, CML, Therapies, Pregnancy, Study Population, Myeloid Malignancies, TKI
Methods: We collected cases of successful pregnancies (conception->childbirth) at 4 CML referral centers including the following conditions: 1/conception occurring while on TKI therapy; 2/TKI therapy stopped for the purpose of conception; and 3/ pregnancy during TKI cessation within a TFR clinical trial. Cases with early spontaneous/elective abortion, treated with interferon during pregnancy or with less than 2 BCR-ABL transcripts recorded during pregnancy were excluded. Doubling time (DT) was calculated using the following formula: DT = ln2/k, where k = (ln(b)-ln(a))/d, where (a) and (b) is the value before the rise and at the rise, and (d) is days.
Results: In total 50 pregnancies in 39 patients were analyzed; 10 patients had >1 pregnancy. Four pregnancies were in the context of TFR study (2 enrolled at conception, 1 patient 28mo in TFR, 1 patient 5mo in TFR). The majority of cases were on first-line treatment at TKI cessation and median duration of TKI therapy was 6.4 years (range 0.5-16.2); 58% were in deeper molecular response (MR4 or deeper) and 34% in major molecular response (MMR) at TKI cessation. Patient characteristics are summarized in Table 1.
Median time off TKI was 10.1 months (range 5.4-71.5). Of 44 pregnancy cases within MMR or deeper at TKI cessation, 54.5% maintained MMR or greater; 60.7% of those in MR4 or deeper and 43.7% for those in MMR, respectively. Several cases were associated with decline in BCR-ABL off TKI: 2 cases of improvement from MMR to deep MR (MR5), and among 4 cases not in MMR at TKI cessation, 1 achieved MMR during pregnancy (Table 2).
BCR-ABL rise in 2 or more consecutive measurements, and at least one measurement of rise defined as more than 2-fold increase, was observed in 24 patients. The median BCR-ABL doubling time among 54 such instances in these 24 patients was 18.3 days (range 1.8-306.8). Of 20 cases that lost MMR during pregnancy, 17 met these criterions for BCR-ABL rise; the median doubling time among 40 such instances in these cases was 14.7 days (1.8-306.8).
Postpartum (n=48), 34 cases have been retreated to date; 14 others remain off therapy with ongoing deep MR (MR5) in 6 cases, MMR in 6 and BCR-ABL <1 (MR2) in 2. Of the 34 cases of retreatment, 5 were not evaluable due to limited time back on TKI (n=3), immediate re-cessation of TKI due to second pregnancy (n=1) or loss of follow-up (n=1). Of the 29 evaluable cases, to date 22 achieved deep MR (MR4 or greater) and 7 achieved MMR. Three patients deemed to not respond adequately after prior TKI resumption switched TKI and achieved MMR or deeper.
Conclusions: BCR-ABL doubling time during TKI cessation for pregnancy was slower compared with that of non-pregnant patients with TKI cessation (TFR) or interruption historically. This retrospective analysis of pregnancy-associated TKI cessation demonstrates overall favorable response stability, with observation of high rates of MMR retention, slowing of BCR-ABL kinetic increase after initial rise, and rare cases of deepening remission over time off TKI. Overall kinetics of BCR-ABL appears variable during pregnancy associated TKI cessation. Given the prominence of pregnancy and family planning as a consideration for TFR attempt and these data, further study of the impact of pregnancy on CML biology, immune function, and relapse risk is warranted.
Disclosures: Kim: BMS: Research Funding; Ilyang: Research Funding; Pfizer: Research Funding; Novartis: Research Funding. Abruzzese: Ariad: Consultancy; Novartis: Research Funding; BMS: Consultancy; Pfizer: Consultancy. Apperley: Incyte: Honoraria, Speakers Bureau; BMS: Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau. Mauro: Pfizer: Consultancy; Novartis: Consultancy, Research Funding; Takeda: Consultancy; Bristol-Myers Squibb: Consultancy.
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