MEETING NEWS
Updates from recent hematology/oncology meetings
Salvage Transplant Versus Continuous Therapy:
Insights From the Myeloma ReLApsE Trial
For patients with multiple myeloma (MM) that has relapsed
following autologous hematopoietic cell transplantation
(AHCT), a standard salvage therapy approach involves high-dose
chemotherapy and AHCT. However, the role of transplant in the
era of continuous treatment with novel agents is in question. At
the 2018 ASH Annual Meeting, investigators presented results
from ReLApsE, the first randomized clinical trial comparing
reinduction, salvage AHCT, and lenalidomide maintenance
therapy with continuous lenalidomide-dexamethasone (Rd)
therapy in this setting.
In the first presentation, principal investigator Hartmut
Goldschmidt, MD, from the University Hospital Heidelberg
and National Center of Tumor Diseases in Germany, shared
the overall findings from the trial; in the second presentation,
coinvestigator Marc-A. Baertsch, MD, also from the University
Hospital Heidelberg, discussed results from a subgroup analysis
of patients with low-risk disease.
ReLApsE is a randomized, open, multicenter trial that
enrolled patients in first to third relapse who had received in-
duction with Rd. Patients were excluded if they had prior salvage
AHCT or were refractory to lenalidomide or had progressive
disease within six months of lenalidomide treatment.
All patients received cycles of Rd; patients with no available
stem cells from earlier harvesting were scheduled to undergo
peripheral blood stem cell mobilization and harvesting. Next,
patients were randomized to receive continuous Rd (arm A;
n=138) or high-dose chemotherapy plus AHCT (arm B; n=139).
Patients were treated until disease progression (with lenalido-
mide maintenance in the salvage-AHCT group and Rd in the
continuous-therapy group).
Patient characteristics were generally balanced between
the two arms: Median ages were 62.2 years in arm A and 61.3
years in arm B; most patients received frontline high-dose
chemotherapy and AHCT (94% and 93%); and most patients
in each arm had International Staging System stage I disease
(60% and 63%). However, “there was an imbalance in terms of
cytogenetics, with a trend toward more high-risk cytogenetics
in the transplant arm (43%) than the continuous arm (32%),”
Dr. Goldschmidt noted.
There were no differences in overall response rate (ORR)
between the two arms:
• ORR (partial response [PR] or better): 75% in arm A vs.
78% in arm B (p=0.57)
• very good PR (VGPR) or better: 47% vs. 49% (p=0.81)
During a median follow-up of 36 months, there also was
no significant difference in progression-free survival (PFS;
primary endpoint) and overall survival (OS) between the two
treatment arms:
• median PFS: 18.8 months in arm A vs. 20.7 months
in arm B (hazard ratio [HR] = 0.87; 95% CI 0.65-1.16;
p=0.34)
• median OS: 62.7 months vs. not reached (HR=0.81;
95% CI 0.52-1.28; p=0.37)
To explain this surprising lack of significant differences be-
tween the arms, Dr. Goldschmidt cited the imbalance in high-
risk cytogenetic features and the fact that 29 percent of patients
in arm B did not receive the planned high-dose chemotherapy
and AHCT intervention.
The investigators conducted a landmark analysis at the fifth
Rd cycle in arm A and at high-dose chemotherapy in arm B.
At this point, there was a trend for improved PFS with salvage
transplant (23.3 months in arm B vs. 20.1 months in arm A;
HR=0.74; p=0.09), as well as improved OS (not reached vs. 57
months; HR 0.56; p=0.05).
The toxicity was “as expected” in patients receiving high-
dose chemotherapy and AHCT, Dr. Goldschmidt reported.
Grade ≥3 adverse events (AEs) were reported in 75 percent
of patients in arm A and 83 percent of patients in arm B, and
incidence of grade ≥3 cytopenias was higher in the high-dose
chemotherapy and AHCT group (leukopenia/neutropenia:
62% vs. 25% [p<0.001], thrombocytopenia: 45% vs. 11%
[p<0.001]).
Approximately one-fourth of the patients completed
treatment per protocol (26% in arm A and 20% in arm B). The
most common reasons for treatment discontinuation in either
arm was progressive disease (54% and 42%). Six patients died
during the study, five in arm A and one in arm B; the authors
noted that no deaths occurred during the high-dose chemo-
therapy and AHCT phase. Also, “there was more treatment
discontinuation due to AEs and less due to progressive disease
in the transplant arm,” he added.
Multivariate analyses revealed that AHCT was associated
with a significant survival benefit in patients with high-risk
cytogenetics (HR=2.71 for PFS and 4.22 for OS; p<0.001 for
both). In his presentation, Dr. Baertsch shared results of anoth-
er subgroup analysis, looking specifically at time to progression
after frontline AHCT (TTP1).
These findings confirmed earlier data showing that length
of TTP1 is a prognostic factor in the salvage setting: In both
arms, patients who had a long TTP1 (≥48 months) had longer
PFS than those with shorter TTP1 (12-24 months; p<0.04) but
did not predict benefit from salvage AHCT or continuous Rd.
In summary, the analyses identified groups of patients who
March 2019
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