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

532s Lymphoma and Plasma Cell Disorders
8090 General Poster Session (Board #37G), Mon, 1:15 PM-5:15 PM
Retrospective analysis of second malignancies in patients with multiple
myeloma. Presenting Author: Giampaolo Talamo, Penn State Hershey
Cancer Institute, Hershey, PA
Background: Recent data from patients with multiple myeloma (MM)
enrolled in randomized clinical trials have shown an increased incidence of
second malignancies after treatment with lenalidomide, but the prevalence
of second malignancies in the overall MM population is uncertain. Methods:
We retrospectively analyzed the medical records of 320 consecutive MM
patients followed at the Penn State Hershey Cancer Institute between
2006 and 2010. We excluded from the analysis basocellular and squamocellular
carcinomas of the skin. Results: Forty-three patients (13%) were
found to have second malignancies, and 5 of them had a third cancer. One
pt had 4 cancers. They included cancers of the prostate (8 pts), breast (8),
MDS/leukemia (6), colon/rectum (5), melanoma (5), lung (4), uterus (4),
bladder (3), kidneys (2), pancreas (2), testicle (1), myeloproliferative
disorders (1), and sarcoma (1). Of 50 cancers, 36 (72%) developed before
the diagnosis of MM, at a median of 65 months (range, 1-372), and 14
after that, at a median of 37 months (range, 3-104). Lenalidomide was
used in 239 (75%) patients, and in 9 of 14 cases of post-MM second
malignancies. Conclusions: Second malignancies usually develop before
the diagnosis of MM, i.e., MM is the second malignancy for the majority of
patients. The use of lenalidomide could not be indicated as a possible
carcinogenic factor for the majority of MM patients with second malignancies.
8092 General Poster Session (Board #38A), Mon, 1:15 PM-5:15 PM
Second autologous stem cell transplantation as a strategy for management
of relapsed multiple myeloma. Presenting Author: Wilson I. Gonsalves,
Mayo Clinic, Rochester, MN
Background: High dose therapy and autologous stem cell transplant (SCT)
remain an integral part of the treatment of multiple myeloma (MM). Despite
the introduction of several new drugs, disease relapse remains inevitable
and a second SCT often allows continued disease control. Methods: We
examined the outcomes in 105 patients (pts) undergoing a second SCT
(SCT2) for relapsed MM, from among 1033 pts receiving initial transplant
between 1994 and 2009. Patients receiving an allogeneic SCT post SCT2
were not included in the survival analysis. Results: Median (range) age at
SCT2 was 60 yrs (35-74) and the time between SCTs was 46 mos
(10-130). The median follow-up was 5 yrs from SCT2. The median (range)
number of regimens between the two SCTs and from diagnosis was 2 (0-7)
and 3 (1-11), respectively. Conditioning regimen was Mel 200 in 85 (81%)
pts. Median (range) CD34 cells infused was 4.6 (2.5-25 million/kg).
Hospitalization was required for 53 pts (50%), median hospital stay was 7
days.. Median time to ANC of 500 and platelets of 50,000 were 13 and 16
days, respectively. Treatment related mortality was seen in 5 (5%) pts. A
partial response or better was seen in 95 (90%) pts, including a stringent
CR in 10%, CR in 19%, and VGPR in 21%. Stable disease or progression
was seen in 7 pts and 3 pts died prior to disease assessment. The median
(95% CI) PFS and OS after SCT2 were 10.4 (8, 14) and 33 (28, 51) mos,
respectively. The median OS was not reached and 33 mos respectively, for
those obtained a CR and those with �CR, P�0.03. FISH pre-SCT2 was
available for 73 pts; the PFS and OS were not affected by the presence of
high-risk MM. In multivariate analyses, shorter duration of response to
SCT1, higher plasma cell (PC) labeling index at SCT2, more regimens used
prior to SCT2 all predicted shorter PFS and OS post SCT2. Lack of CR to
SCT2 was also significantly associated with shorter PFS. Conclusions:
Second SCT is an effective therapy for eligible pts relapsing after other
treatments. It provides a meaningful duration of response and appears to be
well tolerated. Pts with longer duration of response to first transplant and
those achieving a CR appear to have maximum benefit.
8091 General Poster Session (Board #37H), Mon, 1:15 PM-5:15 PM
Predictive value of baseline serum MIP-1� and CRP on symptom burden
and tumor response to induction therapy in patients with multiple myeloma.
Presenting Author: Charles S. Cleeland, University of Texas M. D.
Anderson Cancer Center, Houston, TX
Background: Macrophage inflammatory protein-1�(MIP-1�) is a growth
factor for human multiple myeloma (MM) cells. As an osteoclastic factor,
its presence provides pathophysiological evidence of the development of
lytic bone lesions in MM. C-reactive protein (CRP) indicates systemic
inflammation. The relationship between disease-driven inflammatory markers
and both patient-experienced symptoms and tumor response to induction
therapy is unknown. Methods: MM patients (N�39) who were either
newly diagnosed or had received fewer than 2 cycles of chemotherapy, and
who also were to receive induction therapy, were enrolled. To test
concentrations of MIP-1� and CRP, serum samples were collected before
and after induction and assayed by Luminex. Multiple symptoms were
measured twice a week via the M. D. Anderson Symptom Inventory MM
module (MDASI-MM) from -8 to �112 days of induction. The MM-specific
items of the MDASI-MM are bone aches, constipation, muscle weakness,
diarrhea, sore mouth or throat, rash, and difficulty paying attention.
Correlation between symptom severity and inflammatory markers at baseline
was examined by linear regression modeling. Kruskal-Wallis significance
test and Wilcoxon test were used to examine association between
MIP-1� and tumor response. Results: Patients received either bortezomibbased
(89%) or lenalidomide-based induction therapy. Baseline MIP-1�
and CRP were significantly inversely related to the mean severity component
score of the 5 most-severe symptoms (fatigue, pain, bone aches, poor
sleep, drowsiness) (p�.03; p�.02), and significantly inversely related to
the severity of a component score of the module-specific symptoms
(p�0.04; p�.002). Change over time in MIP-1� differed significantly by
tumor response category (p�.04), with the partial response group having a
higher median score than the complete response group (1.483 vs. 0.016,
p�.01). Conclusions: Our data suggest that higher baseline levels of serum
MIP-1� and CRP predict effective chemotherapy-induced reduction of
disease-related symptoms in MM patients. Higher serum MIP-1� expression
after induction therapy was related to less-ideal tumor response.
8093 General Poster Session (Board #38B), Mon, 1:15 PM-5:15 PM
Prognostic value of serum lactate dehydrogenase in symptomatic multiple
myeloma. Presenting Author: Krina K. Patel, University of Texas M. D.
Anderson Cancer Center, Houston, TX
Background: In patients with symptomatic multiple myeloma, the clinical
features, responses to treatment, and survival times vary. Well established
predictors of survival include the International Staging System (ISS),
cytogenetic abnormalities, and response to therapy. Long recognized has
been the association of high serum lactate dehydrogenase (LDH) with
advanced disease and shorter survival. We focused here on the impact of
high LDH on staging and prognosis in order to guide the role of recent
advances in therapy. Methods: We evaluated 1,247 patients with newly
diagnosed, symptomatic myeloma from 10/74 to 7/11. Our goal was to
determine the prognostic value of high LDH (�300 IU/L) in relation to ISS
stage. We also compared the frequencies of anemia, hypercalcemia, and
response to therapy in patients with high LDH with those of patients with
Stage III disease and normal LDH values. Results: All 1,139 patients with
normal LDH lived significantly longer than the 108 patients with elevated
values (47 vs. 16 months, p �.01). LDH was elevated in 9% of all patients,
but in 2%, 6%, and 18% of patients with ISS-I, II, and III disease,
respectively. Their survival times were also significantly shorter than those
of comparable patients in each stage with normal LDH (table). Among the
108 patients with high LDH, the frequencies of hemoglobin �8.5 g/dl (54
vs. 41%, p�.03), and serum calcium�11.5 mg/dl (41 vs. 27%, p�.01)
were significantly higher than those of 292 patients with Stage III disease
and normal LDH, and the frequency of response to therapy was less (40 vs.
62%, p�.01). Conclusions: Serum lactate dehydrogenase provides a
convenient and dependable prognostic indicator in patients with multiple
myeloma. An elevated LDH value indicates a poor prognosis regardless of
ISS stage, confirming the report by Gkotzamanidou, Terpos, and Dimopoulos
et al, and should be included in the definition of stage III disease. Such
patients require rapid control of disease with sequential combinations of
effective drugs and intensive therapy in order to improve their outcome.
Effect of elevated LDH on survival according to ISS stage (median months).
ISS Stage < 300 IU/L >300 IU/L p
I 56 16 .09
II 49 21 �.01
III 35 16 �.01
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