The survival of adult patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (R/R ALL) who underwent allogeneic hematopoietic stem cell transplantation (HSCT) in the phase 3 TOWER trial (ClinicalTrials.gov identifier: NCT02013167) of blinatumomab compared with standard-of-care (SOC) chemotherapy was driven by response to study therapy and salvage status regardless of on-study HSCT status, according to analyses published in Cancer. Nonetheless, the authors emphasized caution when interpreting the data as the TOWER trial was not designed to prospectively evaluate survival outcomes correlated with HSCT following blinatumomab.
In the TOWER study, researchers randomly assigned 405 patients with R/R ALL in a 2 to 1 ratio to receive either blinatumomab or SOC, with 2 cycles of induction followed by consolidation and maintenance therapy. After the first cycle of induction treatment, patients eligible for HSCT could proceed to HSCT.
In the primary readout of TOWER, blinatumomab was associated with increased overall survival (OS) compared with SOC chemotherapy, with patients in the experimental arm experiencing median OS of 7.7 months (95% CI, 5.6-9.6) compared with 4.0 months (95% CI, 2.8-5.3) in the SOC arm (hazard ratio, 0.71; P =.01).
The 65 patients in the blinatumomab arm who underwent on-trial HSCT had generally similar baseline characteristics to the 32 patients in the SOC arm who underwent on-trial HSCT.
Although undergoing HSCT incurred a survival benefit, there was no difference in benefit between the blinatumomab and SOC arms (P =.68). Descriptive statistical analysis revealed no survival benefit after undergoing HSCT in patients who achieved complete remission with full, partial, or incomplete hematologic recovery with blinatumomab (odds ratio, 1.17; 95% CI, 0.54-2.53).
Overall, patients with no prior salvage therapy and with measurable residual disease response to blinatumomab achieved the best clinical outcomes regardless of on-study HSCT status.
“These data should be interpreted with caution because the TOWER study was not designed to prospectively assess survival with or without HSCT, and the blinatumomab and SOC groups receiving HSCT were not based on randomization,” cautioned the researchers. “It is important to note that no information regarding transplantation-related mortality was collected, and the follow-up after HSCT was limited.”
- Jabbour EJ, Gökbuget N, Kantarjian HM, et al. Transplantation in adults with relapsed/refractory acute lymphoblastic leukemia who are treated with blinatumomab from a phase 3 study. Cancer. 2019;125:4181-4192.