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2104 Challenges of Maintenance Tyrosine Kinase Inhibitor Therapy after Allogeneic Hematopoietic Cell Transplantation in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

Program: Oral and Poster Abstracts
Session: 723. Allogeneic Transplantation: Long-term Follow-up and Disease Recurrence: Poster I
Hematology Disease Topics & Pathways:
Research, Lymphoid Leukemias, ALL, Biological therapies, Clinical Research, health outcomes research, Diseases, real-world evidence, Therapies, Lymphoid Malignancies, Adverse Events, Transplantation, Minimal Residual Disease
Saturday, December 10, 2022, 5:30 PM-7:30 PM

Tamer Othman, MD1,2*, Paul B. Koller, MD3, Ni-Chun Tsai, MS4*, Hoda Pourhassan, MD3*, Vaibhav Agrawal, MD2, Salman Otoukesh, MD3*, Idoroenyi Amanam, MD3, Dat Ngo, PharmD5*, Jason Chen, PharmD5*, Monzr M. Al Malki, MD3, Amandeep Salhotra, MD3, Haris Ali, MD3, Ahmed Aribi, MD3, Karamjeet S. Sandhu, MD3, Shukaib Arslan, MD3*, Brian J Ball, MD3, Forrest M. Stewart, MD3*, Peter T. Curtin, MD3, Andrew S. Artz, MD, MS3, David S Snyder, MD2, Guido Marcucci, MD3, Stephen J Forman, MD3, Anthony S. Stein, MD3, Ryotaro Nakamura, MD2, Vinod A. Pullarkat, MD3*, Ibrahim Aldoss, MD3 and Matthew Mei, MD6

1University of California Davis Comprehensive Cancer Center, Sacramento, CA
2Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA
3Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA
4Department of Computational and Quantitative Medicine-BRI, City of Hope National Medical Center, Duarte, CA
5Department of Pharmacy, City of Hope National Medical Center, Duarte, CA
6Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Medical Center, Duarte, CA

Background:

Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) relapse after allogeneic hematopoietic cell transplantation (HCT) is difficult to manage. One strategy to prevent this is tyrosine kinase inhibitor (TKI) maintenance post-HCT, but the vast majority of data discusses the use of imatinib in this setting, with few reports on newer generation TKIs (NG-TKI). Here, we present our institutional experience with TKI maintenance post-HCT.

Methods:

Ph+ ALL patients who underwent HCT and received TKI maintenance anytime post-HCT from 2003-2019 were included through retrospective chart review. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival (PFS), and cumulative incidence of non-relapse mortality (NRM), cumulative incidence of relapse (CIR), and graft-vs-host disease (GVHD). OS and PFS were calculated via the Kaplan Meier method, NRM, CIR, and GVHD were calculated through a competing risk analysis, where CIR was used as a competing risk for NRM and GVHD, and NRM for CIR and GVHD.

Results:

110 patients were included, and their baseline characteristics are described in Table 1. 45 (40.9%) patients received imatinib initially, and 65 (59.1%) received NG-TKI initially, of whom, 59 (90.8%) received dasatinib, 4 (6.2%) received nilotinib, and 2 (3.1%) received ponatinib. The median age (range) of the initial imatinib and NG-TKI groups were 42 years (19-64) and 47 (21-73), respectively. 25 (55.6%) vs 43 (66.2%) in the initial imatinib vs NG-TKI groups were >40 years, respectively. 18 (40.0%) vs 39 (60.0%) of the patients receiving initial imatinib vs NG-TKI were female (P=0.052). 20 (44.4%) vs 54 (83.1%) patients in the imatinib vs NG-TKI group underwent HCT ≥2010, respectively (P<0.001). 41 (91.1%) vs 57 (87.7%) in the imatinib vs NG-TKI groups underwent HCT in first complete remission (CR1) (P=0.76), and 21 (46.7%) vs 31 (47.7%) had no measurable residual disease (MRD) detected by PCR at the time of HCT, although 10 (22.2%) vs 10 (15.4%) did not have a PCR report at the time of HCT available (P=0.66). 42 patients (38.2%) required a dose reduction due to toxicity, and 67 patients (60.9%) experienced TKI interruption due to toxicity. Initial imatinib vs NG-TKI maintenance was discontinued in 20 (46.5%) vs 29 (44.6%) due to toxicity, respectively. The median cumulative initial TKI exposure in patients initially receiving imatinib and NG-TKI was 354 days (range, 6-4,473) and 301 days (range, 5-2,740), respectively. Reasons for TKI discontinuation are listed in Table 2. There was no difference in 5-year OS and PFS in patients receiving imatinib vs NG-TKI, 84.1% vs 69.8% (P=0.47) and 75.1% vs 62.5% (P=0.48), respectively. Likewise, 5-year NRM, 5-year relapse, and 4-year GVHD were similar between imatinib vs NG-TKI, 9.0% vs 18.3% (P=0.48), 15.9% vs 19.2% (P=0.92), and 40.7% vs 47.7% (P=0.47), respectively. Univariate analyses showed an improvement in OS and PFS in those who received ≥12 months of TKI maintenance vs those who received <12 months, hazard ratio (HR) 0.26 (95% confidence interval (CI), 0.12-0.55), P<0.001 and HR 0.33 (95% CI, 0.17-0.64), P<0.001. There was no difference in OS and PFS for those who completed ≥12 months of TKI maintenance based on initial TKI of choice, HR 0.85 (95% CI, 0.21-3.51), P=0.8 and HR 0.91 (95% CI, 0.28-2.94), P=0.9.

Conclusions:

Our findings demonstrate the challenges of delivering post-HCT TKI maintenance. Toxicity leading to TKI interruptions, discontinuation, and dose reduction was common. Post-transplant outcomes were comparable with imatinib and NG-TKI. Therefore, TKI selection for post-HCT maintenance should be based on patient tolerability to maximize TKI maintenance exposure.

Disclosures: Koller: Treadwell Therapeutics: Other: Safety Review Committee; Takeda: Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Al Malki: NexImmune: Consultancy, Research Funding; Hasna Biopharma: Membership on an entity's Board of Directors or advisory committees; Miltenyi Biotec: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; CareDx: Consultancy, Research Funding; Gilead: Consultancy, Research Funding. Salhotra: BMS: Research Funding; Orca Bio: Research Funding; Kadmon: Other: Advisory board meeting . Ali: Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Incyte Corporation: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Aribi: SeaGen: Consultancy. Ball: Oncovalent: Membership on an entity's Board of Directors or advisory committees. Artz: Magenta: Honoraria; Abbvie: Honoraria. Marcucci: Abbvie: Other: Speaker and advisory scientific board meetings; Novartis: Other: Speaker and advisory scientific board meetings; Agios: Other: Speaker and advisory scientific board meetings. Stein: Amgen: Speakers Bureau. Nakamura: Helocyte Inc: Research Funding; Magenta Therapeutics: Consultancy; Sanofi: Consultancy; Omeros: Consultancy; Kadmon: Consultancy; BluebirdBio: Consultancy. Pullarkat: Amgen, Dova, and Novartis: Consultancy, Other: Advisory Board Member; AbbVie, Amgen, Genentech, Jazz Pharmaceuticals, Novartis, Pfizer, and Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Aldoss: Kite: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; MacroGenics: Research Funding; Sobi: Membership on an entity's Board of Directors or advisory committees; Autolus: Consultancy; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Mei: Novartis: Consultancy; Morphosys: Research Funding, Speakers Bureau; EUSA: Honoraria; Celgene: Research Funding; Beigene: Research Funding; Incyte: Research Funding; CTI: Honoraria.

OffLabel Disclosure: Nilotinib in Ph+ ALL is an off label use

*signifies non-member of ASH