authors also noted that treatment with midostaurin was not as-
sociated with an increased risk or severity of GVHD, compared
with SOC (p values not provided).
Regarding 18-month RFS (the study’s primary endpoint), Dr.
Maziarz said that “both arms did better than predicted,” and there
was a statistically nonsignificant reduction in the relapse risk for
midostaurin-treated patients. The estimated 18-month RFS was
89 percent in the midostaurin arm and 76 percent in the SOC arm
(hazard ratio [HR] = 0.46; 95% CI 0.12-1.86; p=0.27).
At 24-month follow-up, the investigators observed a continued
RFS benefit with midostaurin (85% vs. 76%; HR=0.60; 95% CI
0.17-2.14; p=0.43), although this was not statistically significant.
Midostaurin also appeared to prolong overall survival, but
again, these results did not reach statistical significance.
The investigators also reviewed plasma inhibitory activity
among midostaurin-treated patients, finding that greater inhi-
bition of pFLT3 (>70%) was associated with improved survival
outcomes, while patients with suboptimal pFLT3 inhibition
(<70%) had outcomes that matched SOC-treated patients.
The small patient population of the RADIUS trial limits the
generalizability of its findings, and Dr. Maziarz said that the trial
was underpowered for “determining survival and was instead
looking for a signal [of benefit].” He also noted a potential
internal bias, because patients were enrolled after undergoing
alloHCT and met criteria of good performance status, hemato-
poietic recovery, and adequate organ function.
Dr. Maziarz added that, in real-world clinical practice, most
patients with FLT3-mutated AML are now receiving tyrosine
kinase inhibitors during induction and consolidation therapy,
which also may affect the role of midostaurin as post-transplant
maintenance therapy.
The authors reported relationships with Novartis, which
supported the study.
REFERENCE
Maziarz RT, Fernandez H, Patnaik MM, et al. Radius: Midostaurin (mido) plus standard
of care (SOC) after allogeneic stem cell transplant (alloSCT) in patients (pts) with FLT3-
internal tandem duplication (ITD)–mutated acute myeloid leukemia (AML). Abstract
#13. Presented at the Transplantation & Cellular Therapy Meetings of ASBMT and
CIBMTR, February 20, 2019; Houston, TX.
Non-Engineered T Cells to Prevent or Treat Relapse
in Post-Transplant AML/MDS
Infusion with “non-engineered” adoptive T-cell products
induced responses in select patients with myelodysplastic
syndromes (MDS) and acute myeloid leukemia (AML) who
had undergone allogeneic hematopoietic cell transplantation
(alloHCT) and subsequently relapsed. One complete response
(CR) lasted for 13 months, according to research presented by
Premal Lulla, MBBS, from the Baylor College of Medicine in
Houston, at the 2019 Transplantation & Cellular Therapy (TCT)
Meetings of ASBMT and CIBMTR.
“With this study, we proposed using donor lymphocytes that
have been enriched ex vivo for leukemia reactivity and then
infused back to recipients,” Dr. Lulla explained. “The intention
is to infuse recipients first to prevent relapse and second to treat
ongoing relapsed disease.”
After investigators identified four antigens frequently
expressed in disease cells from patients with MDS/AML
(PRAME, WT1, NYESO1, and Survivin), they developed
donor products that have demonstrated activity against them.
The donor-derived T-cell products were polyclonal, containing
both CD4- and CD8-positive, antigen-specific populations,
and the cells were expanded and enriched in the laboratory
without genetic engineering approaches, Dr. Lulla added.
To determine the safety and efficacy of this T-cell therapy,
the investigators conducted a phase I study that enrolled patients
with MDS/AML into two groups: Group A included patients
whose disease was in remission at the time of infusion; group B
included patients whose disease was in ongoing relapse.
T cells were infused at three escalating dose levels, ranging
from 5×10 6 to 2×10 7 cells/m 2 . Dr. Lulla noted that the products
were successfully manufactured and maintained specificity
against target antigens.
At the time of data presentation, 27 patients (24 with AML, 3
with MDS) were enrolled; 20 patients had been infused with the
T-cell product (13 in group A and 7 in group B).
Infusion of the T-cell products was safe, the authors re-
ported, with only four documented infusion-related adverse
events (AEs): three grade I liver function test (LFT) elevations
and one grade III LFT elevation. “Notably, no patient had
infusion-related cytokine release syndrome, neurotoxicity, or
graft-versus-host disease,” Dr. Lulla added.
Among the 13 patients in group A who were infused, four
patients experienced a relapse, and each relapse occurred between
four and 10 months after T-cell infusion. Of these four patients,
one was moved to group B for additional T-cell treatment and
subsequently experienced a CR that lasted for 13 months. Another
two patients had isolated central nervous system relapse and were
successfully treated with intrathecal chemotherapy without T-cell
infusion. The remaining patient of the four had bone marrow
relapse and was treated with systemic chemotherapy and another
alloHCT and remained alive in relapse at 1.5 years post initial
T-cell infusion.
Seven patients were enrolled in group B. Three patients had
progressive disease, two had stable disease, and two responded to
T-cell treatment. Responders included the patient initially treated
in group A and another who experienced a partial response and
May 2019
19