Dex ± Bortezomib for Advanced Myeloma According to Prior Neuropathy: The Impact of Cytogenetics

Clinical Studies Including Transplantation analysis, we included patients with follow-up period of q 12 weeks or death. Results: 489 patients (56% male, median age, 64 years) were enrolled as of August 29, 2008. In the year before bortezomib therapy, PN was seen in 127 (26%) patients. At baseline, just before initiation of bortezomib therapy, 110 (22%) patients had PN due to previous MM treatment. Most PN cases at baseline were grade 1. Sixty-seven percent of patients started bortezomib in combination with other therapies such as dexamethasone, thalidomide, lenalidomide, and/or prednisone. Of 253 patients with no PN at baseline and q 12-week follow-up, newonset PN was largely grade 1 (21%) or grade 2 (16%). Grade 3 and 4 PN developed in 24 (9%) and 4 (2%) patients, respectively. Of the 82 patients with PN at baseline and q 12-week follow-up, 42 (51%) had PN improvement or resolution at any time during bortezomib therapy, 15(18%) had PN worsening, and 25 (30%) patients had no change in PN. Conclusion: In this international observational study PN was observed in 1 of 4 patients prior to bortezomib therapy. Consistent with clinical trial data, most cases with new-onset PN during bortezomib therapy were mild or moderate in severity. Despite the presence of baseline PN, more than half of these patients had improvement or stabilization of PN during bortezomib therapy.

A135 Bortezomib International Observational Study in Multiple Myeloma: Baseline Characteristics K Zervas,1 R Dhawan,1 M Delforge,2 H Samblanx,3 D Sargin,4 C Hulin,5 M Linderholm, J De la Rubia,6 K Abdulkadyrov,7 R Ganguly,8 J Diels9

Len/Dex ± Bortezomib for Advanced Myeloma According to Prior Neuropathy: The Impact of Cytogenetics

Theageneion Anticancer Hospital of Thessaloniki, Greece;

2

University Hospital Leuven, Belgium;

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ZNA Middelheim, Antwerp, Belgium;

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Istanbul University Istanbul Medical Faculty, Turkey;

5

Centre Hospitalier Universitaire of Nancy-Brabois, France;

MA Dimopoulos, E Kastritis, D Christoulas, M Migkou, M Gavriatopoulou, F Zagouri, M Roussou, E Terpos

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Dept. of Haematology, Linköping University Hospital, Sweden;

Department of Clinical Therapeutics, University of Athens School of

6

La Fe Hospital in Valencia, Spain;

Medicine

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Russian Scientific Research Institute of Hematology and

8

Johnson & Johnson Pharmaceutical Services, Raritan NJ;

9

Johnson & Johnson Pharmaceutical Services, Beerse, Belgium

Introduction: Bortezomib is indicated for the treatment of multiple myeloma (MM). The Electronic VELCADE Observational Study (eVOBS) is a non-interventional study evaluating clinical outcomes of bortezomib therapy in actual clinical practice. Enrollment in Belgium, France, Greece, Russia, Spain, Sweden, and Turkey is scheduled for October 2006 to December 2008. This report includes baseline patient characteristics of relapsed/ refractory (R/R) MM patients to date. Materials and Methods: Adults scheduled to initiate bortezomib for R/R MM were eligible for study. Sociodemographics, chronic comorbidities, and patient characteristics were recorded at baseline. Treatment history was documented retrospectively for 1 year before initiation of bortezomib. After enrollment, all bortezomib dosages and concomitant treatments were permitted. Data on efficacy, safety, and concomitant therapy were collected prospectively for 3 years. Disease staging used Durie Salmon (DS) or International Staging

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1

Transfusiology, Saint-Petersburg, Russia;

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System (ISS) criteria. Results: 489 patients (56% male) were enrolled as of August 29, 2008. Median age was 64 years (range, 33-95 years), with a median of 2 years (range, 0-21 years) since first MM treatment. MM was stage III (ISS or DS) in 47% of patients. Most patients (77%) had q 1 comorbidity at baseline: 22% had 2 and 28% had q 3 comorbidities. 50%, 28%, and 10% of patients were initiated on bortezomib for 2nd, 3rd, and q 4th-line, respectively. The most common prior MM treatments were melphalan/prednisone combinations (23%), thalidomide/ dexamethasone (13%), vincristine/doxorubicin/dexamethasone o cyclophosphamide (12%) and thalidomide monotherapy (11%); 4% received an autograft and 25% had no MM treatment in the prior year. At baseline, before starting bortezomib, 12%, 8%, and 3% of patients had grade 1, 2, and 3 peripheral neuropathy, respectively. Initial bortezomib therapy for R/R MM included monotherapy (33%), + dexamethasone (45%), + thalidomide (7%; mostly + dexamethasone), + lenalidomide (3%), + prednisone (5%), and + chemotherapy (8%). Most patients (84%) received an initial bortezomib dose of 1.3mg/m2. Conclusion: Baseline demographics of R/R MM patients in eVOBS are similar to those in a pivotal bortezomib clinical trial (APEX, N Eng J Med 2005). Several bortezomib combination regimens were used in q 2nd-line MM therapy. This database closely captures real-life practice and should provide valuable information for clinicians.

Introduction: Lenalidomide + dexamethasone (RD) is effective for patients with advanced MM and adding bortezomib (BRD) might enhance activity. Materials and Methods: In an ongoing study, patients with pre-existing peripheral neuropathy grade < 2 receive BRD (B: 1 mg/m2 on days 1, 4, 8, and 11; R: 15 mg daily for 14 days or at a lower dose if creatinine clearance (CrCl) < 30 mL/min) and D 40 mg orally on days 1-4, repeated every 21 days) and those with grade q 2 receive RD (28-day cycle of R according to CrCl on days 1 to 21 and D 40 mg orally on days 1-4 and 1518 for the first 4 cycles and on days 1-4 thereafter). Results: 58 patients have been included so far regardless of renal function but without prior treatment with lenalidomide. Baseline conventional metaphase cytogenetics and FISH for del13q, del17p, add1q21, t(4;14), t(14;16) is performed in all patients. Prophylaxis consists of aspirin 100 mg unless already on coumadine or LMWH. BRD: 26 patients, RD: 32 patients. Median number of prior treatments: 3 (range, 1-8 treatments). Prior treatment with thal: 85% (63% thal resistant), prior treatment with B: 83% (54% B resistant), presence of at least one adverse cytogenetic abnormality by FISH in 45.5%, non-hyperdiploid karyotype in 21%, baseline CrCl < 50 mL/min in

Clinical Lymphoma & Myeloma Supplement February 2009

XII International Myeloma Workshop 29%, high LDH in 19%, ISS 3 in 34%. Forty-nine percent achieved > PR (27% PR, 11% VGPR, 11% CR). Response after BRD and RD was 48% and 50% respectively. Response in thal-resistant and Bresistant patients: 29% and 42% respectively. At least a PR according to del13q, del17q, t(4;14), add1q21 positivity: 35%, 14%, 33%, and 36% of patients, respectively. Eighty-three percent of patients with hyperdiploid and 9% with a non-hyperdiploid karyotype responded (P = .002). DVT occurred in 1 of 46 patients receiving aspirin. After treatment, RANKL serum levels as well as markers of bone resorption (CTX and TRACP-5b) were significantly reduced. The reduction of RANKL and RANKL/osteoprotegerin ratio was higher after BRD than after RD (P = .02). BRD patients also reduced Dkk-1 serum levels, while RD patients showed a slight increase of serum Dkk-1 [p (BRD vs. RD) = 0.01]. In BRD patients, an increase in bone formation markers (bALP and osteocalcin; P = .01) was shown.

A139 Results of ASCT in 34 Patients with Amyloidosis from a Single Center MT Cibeira, M Rovira, J Esteve, L Rosinol, F Fernandez-Aviles, C Martinez, P Marin, E Montserrat, E Carreras, J Bladé Hospital Clínic, IDIBAPS, Barcelona, Spain

Background: Primary amyloidosis (AL) responds poorly to conventional therapy and has poor prognosis. Autologous stem cell transplantation (ASCT) results in a significant response rate though the procedure is hampered by high transplantation-related morbidity and mortality. Aim: To analyze the outcome of a series of 34 patients with AL who underwent ASCT at a single institution during a 10-year period. Patients and Methods: Thirty four patients (16 male, 18 female; median age, 56 years; range, 33-66 years) who received an ASCT between November 1997 and September 2007 were included. Seventeen patients had received previous therapy. In 65% of the patients the light chain was of lambda type. The median number of involved organs was 2 (range, 1-4) including kidney (27 patients), heart (20 patients), liver (12 patients), peripheral nerve (8 patients), autonomic system (6 patients) and gastrointestinal tract (5 patients). Forty-seven percent of the patients had more than 2 organs involved. All patients were mobilized with G-CSF alone and the intensive regimen consisted of MEL-200 in 24 (71%) patients and MEL-140 in 10. The median interval between diagnosis and ASCT was 8.5 months. Results: The overall transplantation-related mortality (TRM) was 26%. There was a trend toward a higher TRM in patients having undergone transplantation from November 97 to April 02 (n = 14; TRM: 42%) as compared to those having undergone transplantation from June 02 to September 07 (n = 20; TRM: 15%; P = .07). The hematologic response rate on an intent-to-treat basis was as follows: CR, 18%; PR, 15%; no response, 32%; early death, 26%; and non-evaluable, 9%. Organ response was observed in 13 patients (38%). The median progression-free survival and the overall survival were 47 and 69 months, respectively. In the first 26 patients transplanted, favorable prognostic features for survival were: cardiac septum < 14 mm (P = .03), normal beta2m (P = .04) and normal NT-proBNP (P = .006). Updated results will be presented at the meeting. Conclusion: (1) ASCT in AL results in prolonged duration

of responses and overall survival, and (2) although TRM is high, there is a trend toward a lower TRM over the years, this most likely reflecting both a better patient’s selection and general management. Cardiac involvement is the main prognostic factor.

A140 Clinical and Immunologic Evaluation of Zoledronate-Activated GD T-Cell–Based Immunotherapy of Myeloma K Suzuki,1 A Nicol,1 Y Abe,2 S Hayashi,2 Y Nakagawa,2 M Nieda,3 K Yokokawa3 1

Centre for Immune and Targeted Therapy, University of Queensland,

Brisbane, Australia; 2Japanese Red Cross Medical Center; 3Medinet Medical Institute, MEDINET Co., Ltd., Tokyo, Japan

Objective: To evaluate the potential anti-tumor activity of zoledronate-activated GD T cells in vivo, we initiated a pilot study involving administration of zoldronate-activated GD T LAK cells to patients with multiple myeloma. Methods: Subjects (n = 6) received 4 intravenous infusions, at 2-week intervals, of zoledroanteactivated GD T LAK cells generated from culture of peripheral blood mononuclear cells (PBMCs) in the presence of zoledroante and IL-2. If M protein in serum levels in a patient remained base line levels following four intravenous infusions, the patient had further 4 treatments at 4-week intervals. The subjects (n = 6) received a median of 0.99 r 109 G9GD T LAK cells per infusion. Results: No serious treatment-related adverse events (only minor systemic side effects, including fever, malaise, and itching) were observed during the study period. The percentage of VG9GD T cells in PBMCS and absolute numbers of VG9GD T cell in PB, in particular those of CD45RA-CD27-effector memory (TEM) VG9GD T-cell subsets increased in all of the patients. The percentage of VG9GD T cells and TEM VG9GD T cells in bone marrow also increased in all of the patients. M protein in serum levels remained baseline levels in 4 of 6 patients and increase in 2 of 6 patients. The serum levels of IFNg in both patients 02 and 06 were under the detection limit before treatment, however, the serum levels detected after the fifth treatments in patient 02 and after the first treatment in patient 06. Also, the expression of NKG2D on GD T cells significantly increased at 24 hours after the first and/or the fourth treatment (P = .0067). Soluble MICA in the serum was detected only in the serum from the patients whose serum levels of M protein resulted in increase. Conclusion: This study indicates for the first time that the administration of zoledronate-activated VG9GD T LAK is a safe and promising immunotherapy approach in the treatment of patients with MM, in particular early stable-stage MM.

A141 Enoxaparin Versus Aspirin Versus Low-FixedDose Warfarin in MM Patients Treated Up Front with Thalidomide A Palumbo,1 M Cavo,1 S Bringhen,2 F Patriarca,3 MT Petrucci,3 M Offidani,3 M Galli,3 R Marasca,3 R Ria,3 C Nozzoli,3 C Crippa,3 L Baldini,3 V Callea,3 N Pescosta,3 M Rizzo,3 E Zamagni,1 A Brioli,1 F Di Raimondo,1 G Gaidano,3 M Boccadoro2

Clinical Lymphoma & Myeloma Supplement February 2009

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