Prognosis in adults with ph-positive B-ALL in first complete remission without minimal residual disease after blinatumomab consolidation is influenced by minimal residual disease (≥10-4) pre-blinatumomab
Year: 2025
Type: conference-abstract
Abstract: Introduction: Outcomes for adult patients (pts) with Philadelphia chromosome-positive (Ph+) B-cell acute lymphoblastic leukemia (B-ALL) have markedly improved in the era of post-remission consolidation with blinatumomab (blina), a bispecific CD19xCD3 T-cell engager (Foa, NEJM 2020; Jabbour, Lancet Haem 2023). Recent evidence suggests pre-blina MRD status is prognostic of post-blina outcomes in Ph- B-ALL (Bassan, Blood 2025). Here, we explored the prognostic significance of pre-blina MRD status for adult Ph+ B-ALL patients in MRD negative remission following blina consolidation. Methods: We retrospectively reviewed pts with Ph+ B-ALL or chronic myeloid leukemia in lymphoid blast crisis (CML-LBC) age ≥18 years who were MRD-negative after receiving ≥1 cycles of blina consolidation during first complete remission (CR1) at the Dana-Farber Cancer Institute (DFCI) and Memorial Sloan Kettering Cancer Center (MSKCC) between 2012 and 2024. MRD was defined as ≥0.01% leukemia cells in the bone marrow as detected by clinical flow cytometry at the treating institution. IKZF1+ genotype was defined as concurrent IKZF1 aberration (deletion or mutation) with CDKN2A/B and/or PAX5 aberrations. All progression free (PFS) and overall survival (OS) analyses were performed from time of post-blina MRD assessment. A multivariable cox proportional hazard model was constructed from variables selected based on clinical relevance to assess effects of IKZF1+ genotype, extramedullary (EM) disease and/or central nervous system (CNS) disease at diagnosis, pre-blina MRD status, number of cycles of blina (1 vs 2+), and subsequent consolidative HCT (salvage HCT excluded; treated as a time-varying covariate) on PFS and OS. Results: A total of 67 pts met eligibility criteria, including 43 (64.2%) pre-blina MRD-negative pts (MRD-) and 24 (35.8%) pre-blina MRD-positive pts (MRD+). Median time from treatment initiation to pre-blina MRD assessment was 62.5 days (IQR 31.2-87.7 days). The MRD- and MRD+ pts did not differ by age (median 58.1 vs. 53.3 years, respectively; p = 0.69), sex (51.7% vs. 44.4% female; p = 0.77), CML-LBC (7.0% vs. 16.7%; p = 0.24), presence of IKZF1+ genotype (14.0% vs. 4.2%; p = 0.41), EM and/or CNS disease at diagnosis (13.9% vs 20.0%; p = 0.71), or receipt of chemotherapy with induction (30.2% vs 20.8%; p = 0.57). During induction, MRD- and MRD+ pts had similar exposure rates to dasatinib (81.4% vs 91.7%, respectively; p = 0.31), ponatinib (14.0% vs. 33.3%; p = 0.11), and other TKIs (11.6% vs. 8.3%; p > 0.99). MRD- pts trended towards a greater number of blina cycles (median 2, range 1-7) than MRD+ pts (median 2, range 1-5; p = 0.06), but the proportion of pts receiving 2+ cycles of blina was similar between MRD- (72.1%) and MRD+ (58.3%) pts (p = 0.29). The frequency of consolidative HCT after blina was similar between MRD- patients (44.2%) and MRD+ patients (66.7%; p = 0.13). With a median follow-up of 2.4 years from post-blina MRD assessment (range 0.20-7.5 years), the median PFS and OS were not reached for MRD- pts versus 3.8 years (p = 0.054) and 5.7 years (p = 0.013), respectively, for MRD+ pts. In the multivariable setting, MRD- status was associated with improved PFS (HR 0.20, 95% CI 0.04-0.88; p = 0.033) and OS (HR 0.04, 95% CI 0.002-0.54; p = 0.016) compared with MRD+ status. No other variables were significantly associated with PFS or OS on multivariable analysis. Overall, receiving consolidative HCT post-blina was not associated with improved PFS (HR 1.27, 95% CI 0.26-6.16; p = 0.76) or OS (HR 0.71, 95% CI 0.09-5.45; p = 0.74). MRD- pts who did (n = 19) versus did not (n = 24) proceed to consolidative HCT had similar PFS (p = 0.74) and OS (p > 0.99). MRD+ pts who did (n = 16) versus did not (n = 8) proceed to HCT also had similar PFS (p = 0.44) but trended towards improved OS (no deaths versus estimated 83.3% [90% CI 38.8-96.6%] OS at 2-years, respectively; p = 0.12). Summary: In a two-institution cohort of adult Ph+ B-ALL pts who were MRD- after blina consolidation in CR1, MRD- status pre-blina was associated with improved survival, irrespective of analyzed covariables. Post-blina HCT was not associated with improved survival, though this may be limited by sample size and follow-up duration. These data suggest pre-blina MRD status is prognostically important even in post-blina MRD- patients. Future studies to assess the role of consolidative HCT in pre-blina MRD+ and MRD- subgroups are encouraged.
Source: Blood
Authors: Benjamin Frost, Yannis Valtis, Yael Flamand, Emilie Baxter, David Nemirovsky, Andriy Derkach, Kuo-Kai Chin, Meira Yisraeli Salman, Leora Boussi, Natalia Tijaro Ovalle, Eytan Stein, Mark Geyer, Shai Shimony, Jacqueline Garcia, Martha Wadleigh, Eric Winer, Virginia Volpe, Maximilian Stahl, Richard Stone, Daniel Deangelo, Jae Park, Marlise Luskin, Evan Chen
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4417019192
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