Author: Roeker LE(1), Dreger P(2), Brown JR(3), Lahoud OB(1), Eyre TA(4), Brander DM(5), Skarbnik A(6), Coombs CC(7), Kim HT(8), Davids M(3), Manchini ST(3), George G(9), Shah N(9), Voorhees TJ(7), Orchard KH(10), Walter HS(11), Arumainathan AK(12), Sitlinger A(5), Park JH(1), Geyer MB(1), Zelenetz AD(1), Sauter CS(1), Giralt SA(1), Perales MA(1), Mato AR(1).
Abstract: Although novel agents (NAs) have improved outcomes for patients with chronic
lymphocytic leukemia (CLL), a subset will progress through all available NAs.
Understanding outcomes for potentially curative modalities including allogeneic
hematopoietic stem cell transplantation (alloHCT) following NA therapy is
critical while devising treatment sequences aimed at long-term disease control.
In this multicenter, retrospective cohort study, we examined 65 patients with
CLL who underwent alloHCT following exposure to ≥1 NA, including baseline
disease and transplant characteristics, treatment preceding alloHCT, transplant
outcomes, treatment following alloHCT, and survival outcomes. Univariable and
multivariable analyses evaluated associations between pre-alloHCT factors and
progression-free survival (PFS). Twenty-four-month PFS, overall survival (OS),
nonrelapse mortality, and relapse incidence were 63%, 81%, 13%, and 27% among
patients transplanted for CLL. Day +100 cumulative incidence of grade III-IV
acute graft-vs-host disease (GVHD) was 24%; moderate-severe GVHD developed in
27%. Poor-risk disease characteristics, prior NA exposure, complete vs partial
remission, and transplant characteristics were not independently associated with
PFS. Hematopoietic cell transplantation-specific comorbidity index independently
predicts PFS. PFS and OS were not impacted by having received NAs vs both NAs
and chemoimmunotherapy, 1 vs ≥2 NAs, or ibrutinib vs venetoclax as the line of
therapy immediately pre-alloHCT. AlloHCT remains a viable long-term disease
control strategy that overcomes adverse CLL characteristics. Prior NAs do not
appear to impact the safety of alloHCT, and survival outcomes are similar
regardless of number of NAs received, prior chemoimmunotherapy exposure, or NA
immediately preceding alloHCT. Decisions about proceeding to alloHCT should
consider comorbidities and anticipated response to remaining therapeutic
options.
