CLINICAL NEWS
tigators conducted a prospective
study to examine the feasibility
and efficacy of a myeloablative
but reduced-toxicity conditioning regimen, which consisted
of fludarabine and busulfan
(FluBu4; fludarabine 40 mg/
m2 per day and busulfan 3.2
mg/kg per day administered
intravenously four times daily).
Compared with other conventional conditioning regimens,
the FluBu4 regimen was less
intense; these regimens typically
consist of intravenous melphalan and cyclophosphamide, the
authors added.
A total of 22 patients with
high-risk or advanced refractory multiple myeloma were
included in the study; 14 of
these patients (64%) had prior
autologous HCT. The median
HCT-specific comorbidity index (HCT-CI) score was three
(range, 0-6), and 46 percent of
patients had some impairment
in their ability to function
(determined by a Karnofsky
performance score of less than
80%).
Among the study participants, 10 had unrelated
donors, three of which were
7/8 human leukocyte antigen
(HLA)–loci matched. Twenty
patients (91%) received GVHD
prophylaxis with tacrolimus
and methotrexate.
Most patients had active
multiple myeloma at transplant,
with a partial response occurring in 12 of 22 patients (46%)
and stable disease in one of 22
patients (4.5%).
All 22 patients tolerated
the FluBu4 conditioning well,
without early toxic deaths or
graft failure. The most common regimen-related toxicities
included mild to moderate
mucositis (82%; n=18) and mild
transient liver function abnormalities (41%; n=9). No grade 4
toxicities were recorded, though
grade 3 mucositis occurred in
Mortality
rates were
comparable
to other
regimens,
but FluBu4
was associated with
high relapse
and chronic
GVHD rates.
32 percent of patients (n=7).
When Dr. Pawarode and
colleagues looked at GVHD
incidence among these patients,
they found that, at day 180, the
cumulative incidence of severe
grade 3 or 4 acute GVHD was
23 percent (95% CI 10-47) and
68 percent (95% CI 46-88) for
chronic GVHD.
For treatment-related mortality, the cumulative incidence
rates were:
• 9% (95% CI 2-33) at day 100
• 19% (95% CI 7-44) at one
year
• 29% (95% CI 13-55) at three
years
Two cases of treatment-related
mortality were due to idiopathic pneumonia syndrome,
and one was due to cirrhosis;
all of these patients had HCTCI scores of greater than three,
indicating pre-transplant organ
dysfunction.
One- and Three-Year Outcomes after
Allo-HCT with FluBu4 Conditioning
TABLE 3.
Cumulative incidence of relapse
1 year
37% (95% CI 20-61)
3 years
50% (95% CI 29-75)
Overall survival
1 year
58% (95% CI 40-83)
3 years
29% (95% CI 15-57)
Progression-free survival
1 year
40% (95% CI 23-67)
3 years
15% (95% CI 5-42)
ASHClinicalNews.org
“The overall outcomes were
not improved because of ongoing high relapse and chronic
graft-versus-host disease rates,”
the authors reported, with poor
progression-free and overall
survival over a median followup of 58.7 months (range =
39-82 months; TABLE 3).
Overall, the use of the myeloablative FluBu4 conditioning with allo-HCT in high-risk
multiple myeloma patients
resulted in treatment-related
mortality rates comparable to
those with other fludarabinebased myeloablative regimens.
For instance, the authors noted,
previous studies have shown
treatment-related mortality
of 19 percent at 100 days and
40 percent at one year with a
fludarabine + melphalan regimen, and 13 percent at one year
with a fludarabine + melphalan
regimen with or without ATG.
However, the relapse rate
was high, including in those
who developed moderate-tosevere chronic GVHD. “This
suggested a less robust graftversus-myeloma effect against
high-risk multiple myeloma,
thus resulting in poor progression-free and overall survival,”
Dr. Pawarode and colleagues
stated. “Nonetheless, the
FluBu4 regimen may be used
as a lower treatment-related
mortality platform [in these
patients].”
Despite these promising
results, there are limitations to
note: First, the current study
was non-comparative in nature,
so definitive conclusions about
the superiority or non-inferiority of FluBu4 regimen over other
regimens could not be made.
The study also included only
22 patients enrolled from one
cancer center, so the regimen
will need to be investigated in
a larger population of myeloma
patients.
Additional strategies (e.g.,
combining a targeted agent with a
GVHD-modulating property, especially a proteasome inhibitor, or
maintenance therapy) are needed
for this high-risk patient population, the authors concluded. ●
REFERENCE
Pawarode A, Mineishi S, Reddy P, et al. Reducing treatmentrelated mortality did not improve outcomes of allogeneic
myeloablative hematopoietic cell transplantation for
high-risk multiple myeloma: a University of Michigan
prospective series. Biol Blood Marrow Transplant. 2015
July 23. [Epub ahead of print]
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