Annual Meeting Proceedings Part 1 - American Society of Clinical ...

520s Lymphoma and Plasma Cell Disorders
8041 Poster Discussion Session (Board #21), Sat, 8:00 AM-12:00 PM and
12:00 PM-1:00 PM
Metronomic therapy for heavily pretreated relapsed/refractory multiple
myeloma (RRMM). Presenting Author: Xenofon Papanikolaou, Myeloma
Institute for Research and Therapy, Little Rock, AR
Background: RRMM represents a true challenge in MM therapy. Based on
the effectiveness of metronomic therapy in solid tumors, we developed a
treatment of metronomically scheduled therapy (MT) for RRMM (Hollmig,
ASH 2004). We are now updating our experience with a median follow up of
25.6 months. Methods: We identified 187 patients treated with MT from
03/2004 to 11/2011. Results: The median age was 61 years (range
36-83); the median number of prior therapies was 14 (range 1-51). 79% of
patients had prior HDT, 99% had a prior exposure to bortezomib, 98% to an
IMiD, and 95% to their combination . The median number of completed
MT cycles was 1 (range 1-5). 63% of patients had a response of MR or
better (6% CR ,7% VGPR, 36% PR, 16% MR). The median overall (OS)
and progression free (PFS) survivals were 11.3 and 3.7 months respectively.
91 of 187 patients had gene expression profiling (GEP) prior to
initiation of MT, of which 53% were high risk according to the 70-gene
(GEP70) risk model. OS was affected by elevated CRP (� 8mg/L,
HR�1.71, p�0.009) and cytogenetic abnormalities within 6 months of
initiation of MT (HR�2.45, p�0.001). For the 91 patients with GEP data
available, OS was correlated with elevated CRP � 8mg/L (HR�2.11,
p�0.009) and GEP70 high-risk (HR�2.65, p�0.001), which also showed
a trend towards shorter PFS. Hematological toxicity grading was difficult as
69% of patients presented with grade ��3 thrombocytopenia within 90
days prior to starting MT. Grade 4 leucopenia , anemia thrombocytopenia
due to MT occurred in 74%, 17%, 89% of patients respectively. Incidence
of grade 4 neutropenic fever was 1%. Grade 4 or worse incidence of all
non-hematological toxicities was below 9%. Most patients were treated in
the outpatient setting (95%) and secondary admissions due to regimen
toxicity occurred in 20%. Conclusions: MT is an effective salvage treatment
in RRMM, with a high ORR and a favorable toxicity profile.
MT regimen.
Agent Days Dosage
Bortezomib 1,4,7,10,13,16 1 mg/m2 Thalidomide 1-16 200 mg
Dexamethasone 1,4,7,10,13,16 20-40 mg
Doxorubicin
1-16 3 mg/m2 IV continuous infusion
hydrochloride
Cisplatin 1-16 1.5-3 mg/m 2 IV continuous infusion
Rapamycin 1-16 3mg on day 1 , 1mg days 2-16
8043 Poster Discussion Session (Board #23), Sat, 8:00 AM-12:00 PM and
12:00 PM-1:00 PM
Long-term results of the phase II trial of the oral mTOR inhibitor everolimus
(RAD001) in relapsed or refractory Waldenstrom macroglobulinemia.
Presenting Author: Irene M. Ghobrial, Dana-Farber Cancer Institute,
Boston, MA
Background: The mammalian target of rapamycin (mTOR) signal pathway
controls cell proliferation and survival. The trial’s goal was to determine the
anti-tumor activity and safety of single-agent everolimus (TORC1 inhibitor)
in patients with relapsed/refractory Waldenstrom macroglobulinemia (WM).
Methods: Eligible patients had measurable disease (IgM monoclonal
protein �1000 mg/dL with �10% marrow involvement or nodal masses �2
cm), a platelet count �75,000 x 106 /L, a neutrophil count �1,000 x
106 /L. Patients received everolimus 10 mg PO daily. Tumor response was
assessed after cycles 2 and 6 and then every 3 cycles until progression.
Results: 60 pts were treated. The median age was 64 years (range, 43-85).
The median number of prior therapies was 3 (range, 1-11). All but two
patients (97%) had received prior rituximab based therapy and 64% of
patients had received prior alkylator based therapies. The overall response
rate (complete response CR� partial response PR� minimal response MR)
was 73% (95% CI: 60-84%), with a PR of 50% and 23% MR. The median
time to progression (TTP), progression-free survival (PFS), and overall
survival (OS) for the entire study population is 28 months (mos), (95% CI:
18-not reached (NR)), 22 mos (95% CI: 12 0-NR), and 55 mos (95% CI:
55-NR), respectively. The estimated PFS at 12 and 24 months is 62%
(95%CI: 51-75%), and 48% (95%CI: 37-63%), respectively. The 30
patients who achieved a PR responded after a median of 2 months (range,
1-26) of treatment. The median duration of response (DR) for these
patients has not yet been reached and 19 of these patients remain in
response after a median follow up of 31 months (range, 3-54). All but two
patients had a decrease in their serum IgM. Grade 3 or higher related
toxicities were observed in 67% of patients. The most common were
hematological toxicities with cytopenias. Pulmonary toxicity occurred in
5% of patients. Dose reductions due to toxicity occurred in 63% of
patients. Conclusions: Everolimus has high single-agent activity with an
overall response rate of 73% and manageable toxicity in patients with
relapsed WM, and offers a potential new therapeutic strategy for this patient
population.
8042 Poster Discussion Session (Board #22), Sat, 8:00 AM-12:00 PM and
12:00 PM-1:00 PM
Detection of the MYD88 L265P mutation in Waldenström’s macroglobulinemia
using a highly sensitive allele-specific PCR assay. Presenting Author:
Lian Xu, Dana-Farber Cancer Institute, Boston, MA
Background: Waldenström’s macroglobulinemia (WM) is a B-cell malignancy
characterized by bone marrow (BM) infiltration with lymphoplasmacytic
cells and production of an IgM paraprotein. By whole genome
sequencing, we recently identified a somatic mutation (L265P) in the
MYD88 gene in 27/30 (90%) WM patients (Treon et al, ASH 2011). To
expand this finding for possible diagnostic testing, we developed an
allele-specific PCR assay for MYD88 L265P and evaluated this assay in a
large cohort of WM patients. Methods: An allele-specific PCR assay was
developed with a threshold of detection of 0.125% for MYD88 L265P.
DNA from bone marrow aspirates from 99 patients with the clinicopathological
diagnosis of WM was used for assessment of MYD88 L265P expression
by both allele-specific PCR and Sanger sequencing. Findings were correlated
with clinical parameters using ANOVA. Results: We observed that
85/99 (86%) WM patients were positive for MYD88 L265P using the
allele-specific PCR assay. Of the 85 allele-specific PCR positive patients,
81 demonstrated a detectable mutation peak by Sanger sequencing. All 14
allele-specific PCR negative patients remained negative by Sanger sequencing.
By the allele-specific PCR assay, MYD88 L265P positive patients
showed greater bone marrow involvement, higher serum IgM and lower
serum IgA and IgG levels versus MYD88 L265P negative patients
(p�0.008). Conclusions: MYD88 L265P is highly expressed in BM samples
of WM patients using an allele-specific PCR assay, and is associated with
greater bone marrow disease burden and serum IgM levels. Use of
allele-specific PCR provides a simple and sensitive diagnostic tool for
detection of the MYD88 L265P mutation.
8044 General Poster Session (Board #32A), Mon, 1:15 PM-5:15 PM
Survival with splenectomy in splenic marginal zone lymphoma: Analysis of
the Surveillance, Epidemiology and End Results (SEER) database. Presenting
Author: Adam J. Olszewski, Alpert Medical School of Brown University,
Providence, RI
Background: The role of splenectomy as the primary therapy for splenic
marginal zone lymphoma has been questioned. We studied relative survival
in SMZL and the impact of splenectomy on lymphoma-specific survival
(LSS). Methods: SMZL cases (diagnosed in 1993-2008) were derived from
the SEER database. Age, sex and race-matched actuarial survival data were
summarized. Factors predictive of splenectomy were studied using logistic
regression with a subsequent propensity score (PS)-weighted survival
analysis. Results: 1071 patients were identified with a median age of 69
years (range, 25-96) and a median follow up of 33 months. 53% were
women and 92% were white. 70% of the lymphomas were stage III/IV with
B symptoms recorded in 22.3%. 54% of patients underwent splenectomy.
The significant factors predictive of surgery included younger age (p�10- 14), stage I/II (p�10-15 ), B-symptoms (p�0.003), no prior malignancy
(p�0.002), with significantly lower rates in black patients (OR 0.41,
95%CI 0.21-0.80, p�0.008), on the Pacific Coast (OR 0.62, 95%CI
0.47-0.81, p�0.0004) and with decreasing rates over time (p�0.0002).
The actuarial 5-year relative survival was 82.8% (95%CI 77.9-86.7%)
with no difference by sex (p�0.79), race or stage. 54% of deaths were
related to SMZL with the estimated LSS of 80.8% (95%CI 78-84%).
Splenectomy was not associated with improved LSS in propensity scorestratified
log-rank test (p�0.60) or in the PS-weighted Cox model
(HR�0.93, 95%CI 0.62-1.38, p�0.70). Advancing age (HR 1.05, 95%CI
1.03-1.07, p�10-8 ) and presence of B-symptoms (HR�1.98, 95%CI
1.30-3.01, p�0.002) were significantly predictive of death from SMZL,
with no evidence of improvement in LSS over the years (HR�0.97,
95%CI�0.91-1.03, p�0.34). There was also no detectable impact of
splenectomy on survival in patients who ultimately died of SMZL (p�0.83).
Conclusions: In this cohort, the largest studied to date, splenectomy did not
demonstrate a survival benefit in SMZL. Patients continue to have
decreased survival despite advances in other indolent B-cell lymphomas.
The role of splenectomy versus chemoimmunotherapy remains to be
determined.
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