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

8053 General Poster Session (Board #33B), Mon, 1:15 PM-5:15 PM
LR-CD: Lenalidomide combination therapy for untreated low-grade B-cell
NHL. Presenting Author: Craig B. Reeder, Mayo Clinic, Scottsdale, AZ
Background: Lenalidomide (LEN) is an immunomodulatory agent that has
shown significant single-agent anti-lymphoma activity in patients with
relapsed disease and in combination may enhance the efficacy of rituximab
by various mechanisms. There is limited data on the role of LEN in
combination regimens for treatment-naïve patients. This phase II single
arm trial was designed to evaluate tumor response, toxicity (AE) and
survival with a combination of LEN, rituximab, cyclophosphamide (CTX)
and dexamethasone (DEX) (LR-CD) in symptomatic untreated patients with
low grade B-cell non-Hodgkin lymphoma. Methods: Eligibility required age
�18, ECOG PS �2, confirmed diagnosis of low-grade B-cell lymphoma
(FL1-2, SLL, MZL or LPL/WM), measurable nodes �2cm or IgM �400mg/
dL(LPL/WM), ANC �1400/mm3 , platelets �100,000/mm3 , creatinine
�2mg/dL, signed informed consent and in need of therapy. Treatment
consisted of IV rituximab 375mg/m2 D1, oral LEN 20mg D1-21, CTX
250mg/m2 D1, 8, 15, DEX 40mg D1, 8, 15, 22 and ASA 325 mg daily in a
28 day cycle. Treatment continued 2 cycles beyond best response (max
12). Toxicity was assessed by NCI CTCAE v3.0. Results: 28 patients have
enrolled at Mayo Clinic with 25 evaluable for toxicity and 21 for response:
Median age 65(43-83), 72% male, FL 24%, MZL 28%, LPL/WM 38%, and
SLL 4%. Median number of cycles given was 5. Overall response in 21
patients with response data is 95% (95% CI 76-100%) with 19% CR (95%
CI 5-42%), and 76% PR (confirmed and unconfirmed, 95% CI 53-92%).
The ORR in 8 patients with LPL/WM with response data was 88%, all PR
(95% CI 47-100%). At a median f/u of 14.7 months 96% are alive without
progression. 1 death (unrelated) occurred 7.7 months after completing 12
cycles of treatment. The most common grade �3 AEs were neutropenia
(37.5%), leukopenia (16.7%), anemia (12.5%) and fatigue (12.5%).
Conclusions: The combination LR-CD with the novel agent LEN is feasible,
well tolerated and produces high response rates in symptomatic patients
with low grade B-cell NHL. Toxicities are manageable and similar to
reported data of single agent LEN.
8055 General Poster Session (Board #33D), Mon, 1:15 PM-5:15 PM
Association of prior rituximab exposure among patients undergoing autologous
stem cell transplantation for relapsed/refractory diffuse large B-cell
lymphoma with inferior outcomes in males compared with females.
Presenting Author: Aleksandr Lazaryan, Taussig Cancer Institute, Cleveland
Clinic, Cleveland, OH
Background: The combination of rituximab with CHOP remains the standard
upfront therapy of patients (pts) with advanced diffuse large B-cell
lymphoma (DLBCL). Gender disparity in survival of pts with DLBCL appears
to be significantly modified by the use of rituximab in both upfront (Ngo,
2008; Pfreundschuh, 2009; Riihijarvi, 2010) and post-transplant maintenance
(CORAL trial) settings. The presence of interaction between gender
and prior rituximab exposure remains unknown in pts with relapsed/
refractory DLBCL undergoing autologous stem cell transplantation (ASCT).
Methods: We conducted a retrospective cohort study of 320 consecutive pts
who underwent ASCT for relapsed/refractory DLBCL at our center from
01/1998 to 12/2010. Relapse-free survival (RFS) and overall survival (OS)
were estimated by Kaplan-Meier method and by Cox proportional hazards
regression analysis in SAS 9.1 (Cary, NC). Results: Among all pts (median
age�54 yrs (IQR, 45-61); 92% Caucasians) 210 (66%) were males and
110 (34%) were females. 85 pts (27%) received more than two prior
chemotherapy regimens. 174 pts (55%) had pre-ASCT exposure to
rituximab as a part of induction or salvage regimens. Preparative regimen
for ASCT uniformly consisted of Bu/Cy/VP-16. In the stratified univariate
analysis of pts treated with rituximab prior to the ASCT, male pts had
inferior RFS (p�0.02; hazard ratio [HR]�1.86, 95% CI, 1.09-3.18) and
OS (p�0.03; HR�1.94, 95% CI, 1.05-3.58). In pts who did not receive
rituximab prior to the ASCT, no difference in RFS or OS according to gender
was observed (all p�0.4). Gender disparity among rituximab recipients was
even more evident for both RFS (p�0.004; HR�2.22, 95% CI, 1.28-
3.83) and OS (p�0.005; HR�2.42, 95% CI, 1.3-4.5) in the multivariable
analyses controlling for age at transplant, number of prior chemotherapies,
and pre-ASCT disease response. Conclusions: Our data support an emerging
concern that male patients with DLBCL have inferior outcomes when
treated with rituximab. The present study has extended this observation to
pts with relapsed/refractory DLBCL treated with ASCT.
Lymphoma and Plasma Cell Disorders
523s
8054 General Poster Session (Board #33C), Mon, 1:15 PM-5:15 PM
Final results of phase I/II trial of vorinostat in combination with cyclophosphamide,
etoposide, prednisone, and rituximab (R-CVEP) for elderly
patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).
Presenting Author: David J. Straus, Memorial Sloan-Kettering Cancer
Center, New York, NY
Background: Standard treatment of relapsed/refractory DLBCL in elderly
patients who are not candidates for autologous stem cell transplantation
(auSCT) has not been established. Cyclophosphamide (C), etoposide (E),
prednisone (P) and procarbazine (CEPP) has been used by many clinicians
based on limited data (Blood 76: 1293-98, 1990). Vorinostat (V) is a
histone deacetylase inhibitor that is approved for relapsed cutaneous T-cell
lymphoma and has activity in B-cell lymphomas. This trial defined the
maximum tolerated dose (MTD) of V added to standard therapy and
determined the response rate of this combination. Methods: Patients �age
60 with relapsed/refractory DLBCL not candidates for auSCT were enrolled
on R-CVEP (R 375mg/m2 IV, d1; C 600mg/m2 d1 and 8, E 70mg/m2 IV d1,
140mg/m2 d2 and 3; V PO and Pred 60mg/m2 PO d1-10) every 28 days for
6 cycles. In the phase I component V was administered at doses of
300mg/d or 400mg/d for 10 days. The phase I was a 3 � 3 design and the
phase II a two stage design requiring 8/20 complete responses (CR) for
expansion. Assessment of response utilized end-of-treatment positron
emission tomography (PET) (JCO 25: 579-86, 2007). Quality of life (QOL)
was measured with the FACT-Lym v.4. Results: 27 pts. were enrolled. 1
died before treatment. For 26 pts: median age 76 yrs. (69-88), 14 females
and 12 males, baseline PS (ECOG) 1 (0-2). Median follow-up for survivors:
9.2 mo. Phase I: 6 pts. at 300mg/d (no dose-limiting toxicity-DLT), 6 pts.
at 400mg/d (2 grade 3 neutropenia � DLT). MTD 300mg/d x 10d. For 20
pts. at V 300mg/m2 (6 phase I � 14 phase II): 2 off study for toxicity, 1
withdrew consent, 6 CR (30%), 5 partial response (PR) (25%), 6
progressed (30%). Phenotypic overall responses (OR): germinal center
(GC) 4/8 (2 CR), non-GC 6/10 (3 CR), transformed CLL 1/2 (1 CR). Median
progression-free survival: 10 mo. QOL results will be presented. Conclusions:
OR rate for V added to conventional chemotherapy and R was 55% (CR
30%, PR 25%) in relapsed/refractory DLBCL in elderly pts. not candidates
for auSCT. This could provide a baseline for comparison with future clinical
trials in this understudied population.
8056 General Poster Session (Board #33E), Mon, 1:15 PM-5:15 PM
Effect of short-duration chemoimmunotherapy plus radioimmunotherapy
on response rates in relapsed follicular lymphoma: A U.K. NCRI Lymphoma
Group Study, CR UK/07/038. Presenting Author: Timothy M Illidge,
Manchester Cancer Research Centre, Manchester, United Kingdom
Background: Radioimmunotherapy (RIT) and rituximab (R) maintenance
have been investigated after chemotherapy (CT) or R-CT in first line
treatment of follicular lymphoma (FL), but less is known about the efficacy
of RIT after R-CT in relapsed FL. This phase II study was conducted to
examine efficacy and safety of abbreviated R-CT followed by 90Y Ibritumomab
tiuxetan in patients with recurrent FL. Methods: Patients (pts) had
FL, at 1st or 2nd relapse after response to R-CT or CT alone. All had
WHO/ECOG performance status �2, and adequate bone marrow (BM),
kidney, liver and cardiac function. BM involvement by lymphoma had to be
�25% prior to infusion of 90Y Ibritumomab tiuxetan, but could be higher at
study entry. Pts received 3 cycles of either R-CHOP or R-CVP, followed by
90Y Ibritumomab tiuxetan (15MBq/Kg, maximum 1200 MBq). No maintenance
R was given. Results: 52 pts were enrolled from 6/2008 to 7/2010.
Median age was 62 years (range 31-87). 46% had high FLIPI score at
entry, 31% intermediate. 80% were at 1st recurrence. Median duration of
best prior remission was 27.7 months. 65% pts had previously received R
and 25% doxorubicin. 71% pts had R-CHOP and 29% R-CVP, prior to RIT.
Overall response rate (ORR) after 3 cycles R-CT was 94% (CR/CRu 10%)
and after RIT ORR 96% (CR/CRu 28%). Grade 3/4 thrombocytopenia
occurred in 58% pts (median duration 16 days): 3/52 pts after R-CT and
27/52 after RIT. Grade 3/4 neutropenia occurred in 62% pts: 15/52 pts
after R-CT and 27/52 after RIT. 5 pts had a total 8 grade 3 infections, only
1 attributable to RIT. 6 pts required platelets and 4 red cell transfusions. 1
pt developed myelodysplasia 10 months after 90Y Ibritumomab tiuxetan,
but no other second malignancy was recorded. PFS was 31.4 months (95%
CI 15.8 - not reached). There was no difference in PFS according to FLIPI
score at entry or reinduction CT (R-CHOP vs R-CVP). Pts with CR/CRu
following RIT showed a trend to improved PFS compared to those with PR
(12 month PFS 90% versus 63%, p�0.06). Conclusions: Abbreviated R-CT
and consolidation with 90Y Ibritumomab tiuxetan is an option for pts with
recurrent FL, with responses of comparable duration to those seen after a
full course R-CHOP.
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