Session: 612. Acute Lymphoblastic Leukemias: Clinical and Epidemiological: Poster III
Hematology Disease Topics & Pathways:
Combination therapy, Lymphoid Leukemias, ALL, Diseases, Treatment Considerations, Lymphoid Malignancies
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.
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