Complete Response Rates Across Biomarker
Subgroups
TABLE.
CAVALLI GOYA IPI 2-5 ΔCR, % (95% CI)
All, n (%) 208 (69.2) 564 (62.8) 6.6% (0-17.6)
BCL2 ICH-positive, n (%) 105 (64.8) 151 (60.3) 4.5% (0-14.1)
BCL2 FISH-positive, n (%) 40 (70) 59 (47.5) 22.5% (6.6-38.5)
Double-expressor, n (%) 81 (66.7) 124 (60.5) 6.2% (0-17.7)
Double-hit, n (%) 7 (71.4) 8 (25) 46.4% (37.2-55.6)
those with double-hit lymphoma. The study was limited by the
reliance on a historical cohort and the lack of a comparator arm.
The authors report relationships with Hoffmann-La Roche and
AbbVie, which supported the trial.
REFERENCE
Morschhauser F, Feugier P, Flinn IW, et al. Venetoclax plus rituximab, cyclophosphamide,
doxorubicin, vincristine and prednisolone (R-CHOP) improves outcomes in BCL2-positive
first-line diffuse large B-cell lymphoma (DLBCL): first safety, efficacy and biomarker
analyses from the phase II CAVALLI study. Abstract #782. Presented at the 2018 ASH
Annual Meeting, December 3, 2018; San Diego, CA.
Rituximab-Lenalidomide Combo Superior to Rituximab
Alone in Relapsed/Refractory Indolent NHL
For patients with relapsed/refractory indolent non-Hodgkin
lymphoma (NHL), adding lenalidomide to rituximab treatment
improved response rates and prolonged time to next treat-
ment, compared with rituximab alone, according to findings
from the phase III AUGMENT trial. John Leonard, MD, of the
Meyer Cancer Center of Weill Cornell Medicine and New York
Presbyterian Hospital, presented the results at the 2018 ASH
Annual Meeting.
The trial met its primary endpoint for improvement in
progression-free survival (PFS) with the lenalidomide and
rituximab (R2) combination, which also was shown to have
a manageable toxicity profile, Dr. Leonard reported. “Taken
together, we believe R2 represents an important new treatment
option for patients with relapsed/refractory indolent non-
Hodgkin lymphoma,” he said.
The AUGMENT trial included 358 patients with marginal
zone lymphoma (MZL) or grade 1 to 3a follicular lymphoma
(FL) who had received at least one prior course of chemotherapy
or immunotherapy, but whose disease was not refractory to ritux-
imab. Refractoriness was defined as achieving less than a partial
response to rituximab or rituximab-chemotherapy or disease
progression within 6 months of last rituximab dose.
After stratification by prior rituximab treatment, time
since last anti-lymphoma treatment, and histology (MZL or
FL), patients were randomized to receive either R2 (n=178) or
rituximab-placebo (n=180) for up to one year.
All patients received rituximab 375 mg/m 2 on days 1, 8, 15,
and 22 of cycle 1, then on day 1 of cycles 2 through 5. Patients in
the R2 group received lenalidomide 20 mg/m 2 on days 1 through
21 of each 28-day cycle, while patients in the rituximab-placebo
group received matched capsules on a similar schedule.
Follow-up continued for five years to evaluate overall survival
(OS), development of second primary malignancies (SPMs), sub-
sequent treatment, and histologic transformations.
Baseline characteristics were well balanced between the two
arms, Dr. Leonard noted. Approximately 60 percent of patients
in each group were ≥60 years of age and approximately 70 per-
cent had advanced-stage disease. The majority in each group had
FL (83% [n=147] in R2 and 82% [n=148] in rituximab-placebo).
The median number of prior anti-lymphoma treatments was
one (range = 1-12), and the most common treatment was ritux-
imab (85% and 83%). Also, about half the patients were enrolled
within two years of their last anti-lymphoma therapy.
Over one year of treatment, 71 percent of patients completed
R2 treatment, while 61 percent completed rituximab-placebo
treatment. “This imbalance was due to the fact that more patients
progressed in the placebo arm (30% vs. 12%),” Dr. Leonard re-
ported, adding that “progression was the most common cause for
discontinuation – not toxicity.”
Adverse events (AEs) were mostly grade 1 or 2 in each arm.
The largest difference in AEs between each arm (≥10%) occurred
with grade 3/4 toxicities, including higher rates of neutropenia,
infections, cutaneous reactions, constipation, leukopenia, anemia,
thrombocytopenia, and tumor flare in the R2 arm.
Histologic transformation was observed in two patients in
the R2 group (1%) and 10 in the rituximab-placebo group (6%),
and fewer patients in the R2 group developed an SPM (3% [n=6]
and 6% [n=10]).
At a median follow-up of 28.3 months (range not report-
ed), R2 was associated with a longer median PFS, assessed by
independent review committee (IRC), than rituximab plus
placebo: 39.4 months (range = 22.9 months to not estimable)
versus 14.1 months (range = 11.4-16.7 months). This translated
to an approximately 54-percent lower risk of death or disease
progression with R2 (hazard ratio [HR] = 0.46; 95% CI 0.34-
0.62; p<0.0001).
All subgroup analysis favored the R2 arm for PFS, except in
patients with MZL, the authors noted. Rates of two-year OS also
appeared to be higher with R2 than rituximab-placebo (93% vs.
87%; p value not reported).
The overall response rate (ORR; a secondary endpoint)
was 78 percent for R2 versus 53 percent for rituximab-placebo
(p<0.0001). Again, the ORR benefit was seen in all subgroups
March 2019
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