-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

4184 The Incidence of CNS Relapse in Philadelphia Chromosome Positive (Ph+) Acute Lymphoblastic Leukemia (ALL) and Its Impact on Clinical Outcome: Results from Consortium on Myeloid Malignancies and Neoplastic Diseases (COMMAND)Clinically Relevant Abstract

Program: Oral and Poster Abstracts
Session: 612. Acute Lymphoblastic Leukemias: Clinical and Epidemiological: Poster III
Hematology Disease Topics & Pathways:
Combination therapy, Lymphoid Leukemias, ALL, Diseases, Treatment Considerations, Lymphoid Malignancies
Monday, December 9, 2024, 6:00 PM-8:00 PM

Kashish J. Shah, MBBS1,2,3*, Mobachir El Kettani, MD1*, Ravi Narra, MD4,5*, Alice Mims, MD6,7,8,9,10,11,12,13,14,15,16, Alexander Coltoff, MD17, Georgio Medawar, MD17, Brooke Hisrich, M.D.18*, Rory M. Shallis, MD19,20,21, Cameron J. Hunter22, Vamsi K. Kota, MD23,24,25,26, Tamer Othman, MD27, Brian A. Jonas, MD, PhD28,29, Shreya Desai, MD26, Guilherme Sacchi de Camargo Correia30*, Anand Ashwin Patel, MD31,32,33,34,35,36, Adam S. Duvall, MD33, Neil D. Palmisiano, MD, MS37, Emily K Curran, MD38,39,40, Zulfa Omer, MD41, Anjali S. Advani, MD42,43,44,45, Ehab L. Atallah, MD46,47,48,49, Mark R. Litzow, MD50,51 and Talha Badar, MD1,52,53,54,55

1Mayo Clinic, Jacksonville, FL
2Department of Internal Medicine, Willis-Knighton Health System, Shreveport, LA
3Department of Hematology and Oncology, Mayo Clinic, Shreveport, LA
4Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
5BMT and Cellular Therapy Program, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
6Division of Hematology, The Ohio State University Comprehensive Cancer Center, Columbus, OH
7Division of Hematology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH
8Division of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH
9The Ohio State University Comprehensive Cancer Center, Columbus, OH
10The Ohio State University, Columbus, OH
11The Clara D. Bloomfield Center for Leukemia Outcomes Research, The Ohio State University Comprehensive Cancer Center, Columbus, OH
12The James Comprehensive Cancer Center, Columbus, OH
13Division of Hematology, The Ohio State University, Columbus, OH
14Clara D. Bloomfield Center for Leukemia Outcomes Research, The Ohio State University Comprehensive Cancer Center, Columbus, OH
15Ohio State University Wexner Medical Center, Columbus, OH
16Arthur G. James Cancer Center Hospital, The Ohio State University Comprehensive Cancer Center, Columbus, OH
17Medical University of South Carolina, Charleston, SC
18Medical University of South Carolina, Charleston
19Section of Hematology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT
20Department of Internal Medicine, Section of Hematology, Yale School of Medicine - Yale Cancer Center, Killingworth, CT
21Cancer Outcomes, Public Policy, and Effectiveness Research (COPPER) Center, Yale University, New Haven, CT
22Department of Internal Medicine, Section of Hematology, Yale School of Medicine - Yale Cancer Center, New Haven, CT
23Augusta University, Augusta, GA
24Georgia Cancer Center, Augusta University, Augusta, GA
25Georgia Cancer Center, Medical College of Georgia, Augusta University, Augusta, GA
26Georgia Cancer Center at Augusta University, Augusta, GA
27Department of Internal Medicine, Division of Hematology and Oncology, University of California San Francisco, San Francisco, CA
28UC Davis Comprehensive Cancer Center, Davis, CA
29Department of Internal Medicine, Division of Malignant Hematology/Cellular Therapy and Transplantation, University of California Davis School of Medicine, Sacramento, CA
30Department of Hematology and Oncology, Mayo Clinic, Jacksonville, FL
31University of Chicago, Chicago, IL
32University of Chicago, Memphis, TN
33Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL
34Section of Hematology/Oncology, University of Chicago, Chicago, IL
35Department of Medicine, Section of Hematology/Oncology, University of Chicago Medical Center, Chicago, IL
36Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL
37Rutgers Cancer Institute of New Jersey, New Brunswick, NJ
38University of Cincinnati, Cincinnati, OH
39Hematology/Oncology, University of Cincinnati, Cincinnati, OH
40Division of Hematology/Oncology, University of Cincinnati Cancer Center, Cincinnati, OH
41Division of Hematology, University of Cincinnati, Cincinnati, OH
42Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH
43SWOG, Ann Arbor, MI
44Cleveland Clinic Foundation, Cleveland, OH
45Translational Hematology and Oncology Research, Cleveland Clinic, Taussig Cancer Institute, Cleveland, OH
46Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
47Medical College of Wisconsin, Milwaukee, WI
48Division of Hematology/Oncology, Medical College of Wisconsin, Milwaukee, WI
49Medical College of Wisconsin, Milwaukee
50Mayo clinic, Rochester
51Division of Hematology, Mayo Clinic, Rochester, MN
52Department of Hematology/Oncology, Mayo Clinic, Jacksonville, FL
53Division of Hematology & Medical oncology, Mayo clinic cancer center, Jacksonville, Florida, Jacksonville, FL
54Division of Hematology-Oncology, Blood and Marrow Transplantation Program, Mayo Clinic, Jacksonville, FL
55Division of Hematology and Oncology, Mayo Clinic, Jacksonville, FL

Background

While central nervous system (CNS) disease is found in minority of patients (pts) at diagnosis of Ph+ ALL, later relapses can occur in pts despite adequate CNS prophylaxis. CNS disease can be managed with varying combinations of systemic, radiation, and intrathecal (IT) therapy and can be associated with significant toxicity, especially in older pts. While there are more durable systemic responses with 2nd or 3rd generation tyrosine kinase inhibitors (TKIs) based combinations, CNS penetration can vary by TKI. In this large multi-center study, we analyze the incidence of CNS disease in Ph+ ALL in the context of induction therapies and survival post relapse.

Methods

We conducted a multicenter observational study in collaboration with 10 U.S. academic centers under the COMMAND consortium and reviewed the incidence of CNS relapse in 505 Ph+ ALL pts. We evaluated baseline characteristics, treatment given prior to CNS relapse, and outcome post relapse.

Results

Baseline characteristics, initial treatment and outcome prior to CNS relapse

Eighteen (3.56%) pts were identified to have CNS disease at relapse. Median age of the pts in years (yrs) was 51 (range [R], 22-75), median white blood cell (WBC) was 33.3 x 10(9)/L (R, 2.1-200) and 6 (33%) pts had additional cytogenetic abnormalities at diagnosis. Sixty-one percent (n= 11) of pts received intensive chemotherapy (IC) during induction; 2 (11%), 14 (78%) and 2(11%) of pts received 1st, 2nd or 3rd generation TKI-based combination during induction, respectively. All of pts achieved complete remission (CR), 45.5% achieved complete molecular remission (CMR) at 3 months from the time of diagnosis. Five (28%) pts received allogeneic stem cell transplantation (allo-HCT) as a consolidation therapy.

Treatment received at CNS relapse and response

The median time to CNS relapse after induction was 10.8 months (mo) (R, 2-79). All pts except 1 had isolated CNS relapse after CR1, 4/18 (22%) pts had T315I mutation at relapse. Twelve (67%) and 6 (33%) pts received intrathecal chemotherapy (IT) with TKI and systemic chemotherapy + TKI in addition to IT, respectively. Eleven (61%) pts received dasatinib, 5 (28%) pts received ponatinib and one (6%) pts each received bosutinib and imatinib at relapse. Ninety-three percent of pts achieved CR (n=3, not evaluable). Six (33%) pts underwent allo-HCT after CNS relapse, one of these transplanted pts had second allo-HCT.

Survival after CNS relapse

The median relapse free survival (RFS) and overall survival (OS) after CNS relapse was 9.8 (95% CI: 3.80-15.76) and 13.87 (95% CI: 4.08-23.65) mo, respectively. In subset analysis, we compared survival outcome among pts who had relapse without CNS involvement (n= 160/505 [32%]). The median RFS (9.9 vs 9.8, p= 0.88) and OS (31.53 vs 28.80, p= 0.57) after relapse was not significantly different among pts who had relapse with or without CNS involvement, respectively. We also compared OS among pts without relapse to those with relapse. The median OS was not reached (NR; 73% alive at 5 years), 28.80 and 31.53 months (p= <0.001) among pts with no relapse, relapse with CNS and without CNS involvement, respectively.

Conclusion

Our retrospective analysis from a large database showed that CNS relapses were uncommon (3.56%) in adult pts with Ph+ ALL. A majority of pts (89%) received a 2nd or a 3rd generation TKI during induction. Approximately one quarter of pts with CNS relapse had emergence of T315I mutation. While almost all pts achieved CR, the RFS was relatively short. We did not see significant differences in survival among pts who had relapse with or without CNS involvement.

Disclosures: Mims: Leukemia and Lymphoma Society Beat AML Study: Other: Senior Medical Director; Treadwell Therapeutics: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Daiichi Saynko: Membership on an entity's Board of Directors or advisory committees; Foghorn Therapeutics: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Shallis: Rigel: Consultancy, Honoraria; Kura Oncology: Consultancy, Honoraria; Servier: Consultancy, Honoraria, Other: Steering Commitee; Gilead Sciences, Inc: Consultancy, Honoraria. Kota: Kite Pharma: Honoraria; Pfizer: Honoraria; Novartis: Honoraria. Jonas: Loxo Oncology: Research Funding; Celgene: Research Funding; Aptose: Research Funding; AROG: Research Funding; Amgen: Research Funding; Rigel: Consultancy, Other: Travel; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kymera: Consultancy, Membership on an entity's Board of Directors or advisory committees; GlycoMimetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech/Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Daiichi-Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; F. Hoffman-La Roche: Research Funding; Forma Therapeutics: Research Funding; Forty-Seven: Research Funding; Hanmi: Research Funding; Immune-Onc: Research Funding; Incyte: Research Funding; Jazz: Research Funding; Pharmacyclics: Research Funding; Sigma Tau: Research Funding; Treadwell: Research Funding. Patel: Bristol Myers Squibb: Honoraria; AbbVie: Honoraria; Sobi: Honoraria; Pfizer: Research Funding; Sumitomo: Research Funding; Kronos Bio: Research Funding. Palmisiano: Abbvie: Consultancy, Research Funding; BMS: Consultancy; Rigel: Consultancy. Curran: Servier: Honoraria; Pfizer: Consultancy; Dava Oncology: Honoraria; Jazz Pharmaceuticals: Consultancy; Kite Pharmceuticals: Consultancy; Clincal Care Options: Honoraria. Advani: Seattle Genetics: Research Funding; Servier: Research Funding; Web MD: Honoraria; Immunogen: Research Funding; Macrogenics: Research Funding; American Society of Hematology: Honoraria; PER: Honoraria; OBI: Research Funding; Incyte: Research Funding; Emmes: Honoraria; Glycomimetics: Research Funding; BEAM: Other: Research support, Research Funding; Wolters Kluwer: Honoraria; Kite: Consultancy, Research Funding; MJH Life: Honoraria; Pfizer: Other: Manuscript help, Research Funding; Amgen: Research Funding; Springer: Honoraria; MD Education: Honoraria; Wiley: Honoraria; Kura: Research Funding; Novartis: Consultancy. Atallah: Novartis Pharmaceuticals Corporation: Honoraria. Litzow: Abbvie: Research Funding; Amgen: Research Funding, Speakers Bureau; Actinium: Research Funding; Astellas: Research Funding; Pluristem: Research Funding; Sanofi: Research Funding; Beigene: Speakers Bureau; Biosight: Other: Data Safety Monitoring Committee. Badar: Takeda: Other: advisory board ; Morphosys: Other: Advisory Board; pfizer: Other: Advisory board.

*signifies non-member of ASH