Outcome of Patients (pts) with Chronic Myeloid Leukemia (CML) Treated with Tyrosine Kinase Inhibitors (TKI) Who Have a History of Prior Malignancies,
Authors: Koller Paul B , Kantarjian Hagop M , Koller Charles , Jabbour Elias , O'Brien Susan , Verstovsek Srdan , Borthakur Gautam , Estrov Zeev , Quintas-Cardama Alfonso , Cortes Jorge E 
Published: October 2019

Abstract
Abstract 3787

Background:
The natural history of CML has been irrevocably changed since the advent of TKIs with pts living longer than they ever have. Some patients have a history of previous cancers by the time they are diagnosed with CML. These pts' long-term prognosis has never been previously described. Aims: To determine the effect of prior malignancy on patient outcome after diagnosis of CML. Methods: The primary objective was to determine outcome of pts with a previous diagnosis of malignancy (PM) vs a group without (nPM). Patients included in clinical trials of TKI as initial therapy for CML in chronic phase from July 2000 to January 2011 were reviewed. Results: Of the 471 CML pts treated with frontline TKIs 47 (10%) had a PM before their CML diagnosis and 5 (1%) pts PM status could not be obtained. The median age of the patients with a PM was 60 (30–84) compared to 46 (15–86) for those with no PM. There were no significant differences in clinical characteristics between PM and nPM patients. The median from diagnosis of a PM and a diagnosis of CML was 69 months (mo) (7 mo to 707 mo). The five most common PMs were: non-melanoma skin cancer in 14 (30%), breast cancer in 10 (21%), melanoma in 5 (11%), colorectal cancer in 5 (11%), and prostate cancer in 5 (11%). “Six pts (13%) had more than one PM and 2 of those 6 had 3 PM before the diagnosis of CML, the other 4 pts had 2 PM. The PMs were treated prior to the diagnosis of CML in the following ways: 17 (36%) pts received chemotherapy for their PM, 17 (36%) received radiotherapy, and 43 (91%) received surgery. At the time of CML diagnosis 3 (6%) pts had active cancer, while the remainder of the pts with a PM were thought to be in remission. Two (4%) pts were on active therapy for their prior cancer diagnosis at the time they started on CML therapy (Tamoxifen for breast cancer in both). After the diagnosis of CML, 6 (13%) pts had a recurrence of their PM including 2 pts with basal cell cancer, and 1 each with melanoma, breast cancer, prostate cancer, and lymphoma. These recurrent malignancies were treated as follows: 3 with radiation, 2 had surgery, and 2 with chemotherapy. Five of these 6 pts continued TKI while receiving therapy for PM. The median time between diagnosis of CML and relapse of PM was 18 months. Median remission of the PM was 151 months. Also, 6 (13%) pts had a new malignancy after CML diagnosis: 2 pts with squamous skin carcinoma, and 1 each with chronic lymphocytic leukemia, papillary thyroid carcinoma, mucoepidermoid carcinoma, and large B-cell lymphoma. Treatments for the new onset malignancy after the diagnosis of CML include: surgery (4), chemotherapy (2), radiation (1), and observation (1). The median time between diagnosis of CML and a new malignancy was 39 months. Six of the 47 pts are deceased: 2 died of their PM, 2 died secondary to treatment complications for their PM, 2 died of cardiovascular issues unrelated to a cancer diagnosis. None died of CML. Initial treatment for CML was imatinib 400mg in 4/47 (9%) PM and 69/419 (16%) nPM, imatinib 800mg in 15/47 (33%) PM and 189/419 (45%) nPM, dasatinib in 11/47 (24%) PM and 78/419 (19%) nPM, and nilotinib in 16/47 (35%) PM, and 83/419(20%) nPM. The outcome of pts with PM and nPM is presented in Table 1. There was no significant different in patient outcome between pts with PM and nPM. Conclusion: Pts with CML who have prior malignancies have the same excellent outcome as patients with no prior malignancies. In the few instances in which concomitant therapy for other malignancies was required during therapy with TKI this could be accomplished with no significant toxicity. Thus, the history of prior malignancy in a patient who develops CML should not affect the decision to treat with TKI.

Disclosures:
Cortes: Pfizer Inc: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding.