The number of prior novel agents administered or their use immediately prior to allogeneic hematopoietic stem cell transplant (alloHCT) for the treatment of chronic lymphocytic leukemia (CLL) was not associated with outcomes, according to results of a retrospective study published in Blood Advances.1
Novel agents such as BCR, BTK, PI3K, and BCL2 inhibitors have generally improved outcomes among patients with CLL, but a subset of patients experience disease progression, resistance, high-grade transformation, or drug intolerance and require additional curative modalities.
“Understanding outcomes for potentially curative modalities including alloHCT following novel agent therapy is critical while devising treatment sequences aimed at long-term disease control,” the authors wrote.
This multicenter, retrospective cohort study included 65 patients with CLL who underwent alloHCT. All patients had received at least 1 novel agent prior to their transplant. Patient-related and disease-related characteristics were assessed, as well as prior treatment and transplant characteristics.
At baseline, the median patient age was 50 years at CLL diagnosis and 60 years at alloHCT. The HCT-comorbidity index (CI) was 0 among 38% of patients, 1-2 among 37%, and ≥3 among 25%. The majority of patients received a reduced-intensity conditioning regimen and a calcineurin inhibitor with methotrexate as graft-vs-host (GVHD) prophylaxis. The median number of previous lines of therapy was 3, with a median of 1 prior novel agent.
At 24 months, the progression-free survival (PFS) was 63% and overall survival (OS) was 81%. Nonrelapse mortality was 13% and relapse occurred among 27% of patients.
The number of novel agents used prior to transplant and the timing of their use was not associated with PFS or OS. In univariate analyses, there was no association between PFS and prior use of ibrutinib, venetoclax, PI3K inhibitors, ≥2 novel agents, or novel agent use immediately before alloHCT. Results were similar for OS.
Poor-risk characteristics, complete vs partial remission, and transplant characteristics were also not associated with PFS after transplant.
Multivariate analysis, however, demonstrated that HCT-CI ≥1 was significantly associated with PFS (hazard ratio, 3.3; 95% CI, 1.1-9.9; P =.035).
The authors concluded that “prior novel agents do not appear to impact the safety of alloHCT, and survival outcomes are similar regardless of number of novel agents received, prior chemoimmunotherapy exposure, or novel agent immediately preceding alloHCT.”
Roeker LE, Dreger P, Brown JR, et al. Allogeneic stem cell transplantation for chronic lymphocytic leukemia in the era of novel agents. Blood Adv. 2020;4:3977-3989. doi:10.1182/bloodadvances.2020001956