Prednisone (VTP) in Elderly

XII International Myeloma Workshop Table 1 Visit

Abstract 146 Mean (SD) ESA Mean (SD) Mean (SD) dose (IU/wk) Hb (g/dL) WHO/ECOG

Percent of Percent of Percent of Patients with Patients on Patients ESA Dose Iron (All Types) on IV iron Escalation

Response Rates

Percent of Patients

Visit 1

30237 (7509)

9.2 (1.0)

1.17 (0.84)

13.7%

4.9%

4.9%

Hb kq 1g/dL

72.2%

Visit 2

30676 (8012)

10.3 (1.5)

0.87 (0.66)

9.2%

4.2%

4.2%

Hb kq 1g/dL within 8 weeks

68.5%

Visit 3

30760 (8698)

11.0 (1.7)

0.86 (0.73)

7.8%

3.6%

3.6%

Hematopoietic response

50.7%

P Value

NS

< .001

< .001

NS

NS

NS

Hb kq 2g/dL

47.1%

maintenance was 9.96 months. Maintenance treatment in the 111 patients randomized to either Thal/IFN or IFN only did not result in significant differences in OS (median from start of maintenance: 53.1 months vs. not reached; P = .49). Overall survival after start of maintenance treatment by induction therapy did not differ between patients pre-treated with MP (53.1 months) or Thal/Dex (43.1 months; P = .41). Patients on Thal/Dex had more grade 1-3 neuropathy and dose reductions or treatment discontinuations. Maintenance IFN was generally well tolerated. Conclusion: In conclusion, patients randomized to maintenance therapy comprise a more favorable prognostic subgroup which is manifested by a longer median survival (62.9 months) compared to the entire patient cohort started on firstline therapy (44.6 months). Overall survival did not differ significantly between patients randomized to Thal/IFN or IFN (53.1 months vs. not reached). Likewise, no difference was observed when survival after start of maintenance was analyzed by first-line therapy.

No significant differences were observed in RR: q PR in 78% of patients in VMP and VTP groups, with a CR rate of 18% versus 23% (P = NS). Regarding hematologic toxicity, VMP resulted in higher incidence of q G3 neutropenia (34% vs. 19%; P = .009) and thrombocytopenia (21% vs. 9%; P = .01); in contrast, 157 related nonhematologic AEs occurred in VTP arm versus 133 in the VMP arm (P < .005); and they were q grade 3 in 32% versus 25% (P = .04). The most relevant toxicities were: q grade 3 cardiac toxicity (7% in VTP vs. 0% in VMP); q grade 3 thromboembolic events (3.4% in VTP vs. < 1% in VMP; q grade 3 PN (15% in VTP vs. 9% in VMP). Five patients in VMP and 7 in VTP died due to AEs. In summary this initial analysis indicates that there are no significant differences in terms of efficacy between VMP and VTP, while the incidence of nonhematologic AEs, specially cardiac events, was higher in the VTP arm, resulting in more serious AEs and treatment discontinuations

A154

A155

Bortezomib (Velcade)/Melphalan/Prednisone (VMP) Versus Velcade/Thalidomide/Prednisone (VTP) in Elderly

Neurologic Monitoring Reduces the Incidence of Bortezomib-Induced Peripheral Neuropathy in MM

MV Mateos, ML Martín, Y Gonzalez, JJ Lahuerta, J Bladé, A Oriol, J Martinez, MT Cibeira, R de Paz, MJ Terol, J Garcia, E Bengoechea, R Martinez, A Martin, F de Arriba, L Palomera, JM Hernandez, JL Bello, J San Miguel

J Petit,2 R Velasco,1 V Clapés,2 J Bruna1

GEM/PEthema

Introduction: Peripheral neuropathy (PN) is the dose-limiting toxicity of bortezomib (BTZ), affecting up to 35% of patients. Bortezomib-induced PN (BIPN) is unpredictable though has been related to some risk factors such as cumulative dose, baseline-PN and diabetes mellitus. Aim: To evaluate the usefulness of continuous neurologic assessment to prevent PN in MM patients on BTZ and to identify prognostic factors related to BIPN. Patients and Methods: Fifty-one resistant/progressing MM patients treated with BTZ were reviewed. Demographics, clinical, MM isotype, disease status, previous therapies, and BTZ dose and toxicities including PN grade were registered. Eighteen patients were evaluated prospectively by a neurologist (NRL-group) with neurologic and electrophysiological exams every two BTZ cycles to warn the treating physician to modify BTZ dose. The remaining 33 formed the control group (Non-NRL). Impact of single parameters on BIPN was determined by univariate and multivariate analyses. Results: Five (28%) patients in the monitored NRL group and 18 (56%) in Non-NRL developed BIPN (P = .043). Grade 3-4 PN

MP has been the standard of care for elderly MM patients in the past 40 years. However, bortezomib and thalidomide–based combinations have been demonstrated to improve the response rate and time to events. In April 2006, Spanish Myeloma Group activated a phase III trial comparing VMP versus VTP in elderly untreated MM patients. Patients in the VMP arm received intravenous bortezomib 1.3 mg/m2 twice weekly (days 1, 4, 8, 11, 22, 25, 29, and 32) for one 6-week cycle , followed by once weekly (days 1, 8, 15, and 22) for five 5-week cycles in combination with oral melphalan 9 mg/m2 and prednisone 60 mg/m2 on days 1-4. Patients in the VTP arm received the same bortezomib and prednisone regimen, but they received continuous thalidomide at dose of 100 mg daily. As of July 30, 2008, 246 out of 260 planned patients have been included in the study and 167 are evaluable for response to induction therapy and safety. Eighty patients were randomly assigned to receive VMP and 87 to VTP.

1

Neuro-Oncology Unit, IDIBELL (Department of Neurology, Hospital

Universitari de Bellvitge); 2Clinical Haematology (Institut Català d’Oncologia), Barcelona, Spain

Clinical Lymphoma & Myeloma Supplement February 2009

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