APRIL 2011

Phase II trial of high-dose topotecan, melphalan and CY with autologous stem cell support for multiple myeloma.
Bone Marrow Transplant. 2011 Apr;46(4):510-5.
Kazmi SM, Saliba RM, Donato M, Wang M, Hosing C, Qureshi S, Anderlini P, Popat U, Champlin RE, Giralt SA, Qazilbash MH.
Median progression-free survival in 60 patients treated with autologous SCT, using topotecan, cyclophosphamide, and melphalan as conditioning regimen, was 18.5 months, similar to the PFS seen with high-dose melphalan.

Comparison of immunofixation, serum free light chain, and immunophenotyping for response evaluation and prognostication in multiple myeloma.
J Clin Oncol. 2011 Apr 20;29(12):1627-33.
Paiva B, Martinez-Lopez J, Vidriales MB, Mateos MV, Montalban MA, Fernandez-Redondo E, Alonso L, Oriol A, Teruel AI, de Paz R, Laraña JG, Bengoechea E, Martin A, Mediavilla JD, Palomera L, de Arriba F, Bladé J, Orfao A, Lahuerta JJ, San Miguel JF.
This is a prospective study comparing the prognostic impact of conventional CR (= negative immunofixation + <5% plasma cells in the bone marrow), stringent CR (= CR + normal serum free kappa/lambda ratio), and immunophenotypic remission (= flow cytometry negative) in 102 patients with newly diagnosed multiple myeloma. Discrepancies between the results of the three techniques were common. Patients in stringent CR did not have a survival advantage compared with patients in conventional CR (but follow-up was limited). Instead, patients with negative flow cytometry had a better progression-free survival and overall survival than patients in conventional CR or stringent CR. Interestingly, patients with negative flow cytometry but positive immunofixation had a better prognosis than patients with positive flow cytometry and negative immunofixation. In fact, in patients with negative flow cytometry, the paraprotein disappeared with time, whereas patients with positive flow cytometry and negative immunofixation eventually experienced reappearance of the paraprotein and disease relapse/progression. In conclusion, the achievement of remission by flow cytometry led to longer remissions than the achievement of CR by immunofixation or free light chain ratio.

Previous thalidomide therapy may not affect lenalidomide response and outcome in relapse or refractory multiple myeloma patients.
Eur J Cancer. 2011 Apr;47(6):814-8.
Guglielmelli T, Bringhen S, Rrodhe S, Gay F, Cavallo F, Berruti A, Montefusco V, Piro E, Benevolo G, Petrucci MT, Caravita T, Offidani M, Corradini P, Boccadoro M, Saglio G, Palumbo A.
Among 80 patients with multiple myeloma resistant to thalidomide, treatment with lenalidomide induced a response rate of 56%. Median progression-free survival was 10 months, and median overall survival 17 months.


MAY 2011

Phase I study of the anti insulin-like growth factor 1 receptor (IGF-1R) monoclonal antibody, AVE1642, as single agent and in combination with bortezomib in patients with relapsed multiple myeloma.
Leukemia. 2011 May;25(5):872-4.
Moreau P, Cavallo F, Leleu X, Hulin C, Amiot M, Descamps G, Facon T, Boccadoro M, Mignard D, Harousseau JL.
26 patients with relapsed/refractory myeloma received AVE1642, a humanized monoclonal antibody against CD221, the insulin-like growth factor-1 receptor. Among the first 15 patients treated with single agent AVE1642, there was only 1 minor response. Therefore, the activity of this agent was overall negligible (but we need to acknowledge the important limitations of assessing clinical benefit in a phase I study).

Pamidronate versus observation in asymptomatic myeloma: final results with long-term follow-up of a randomized study.
Leuk Lymphoma. 2011 May;52(5):771-5.
D'Arena G, Gobbi PG, Broglia C, Sacchi S, Quarta G, Baldini L, Iannitto E, Falcone A, Guariglia R, Pietrantuono G, Villani O, Martorelli MC, Mansueto G, Sanpaolo G, Cascavilla N, Musto P; Gimema (Gruppo Italiano Malattie Ematologiche Dell'Adulto); Multiple Myeloma Working Party; Gisl (Gruppo Italiano Studio Linfomi) Cooperative Group.
177 patients with asymptomatic myeloma were randomized to pamidronate vs observation. After a minimum follow-up of 5 years, pamidronate reduced the skeletal-related events at progression (39% vs 72%), but neither EFS (46 vs 48 months, NS) nor overall survival were improved.

Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study.
Lancet Oncol. 2011 May;12(5):431-40.
Moreau P, Pylypenko H, Grosicki S, Karamanesht I, Leleu X, Grishunina M, Rekhtman G, Masliak Z, Robak T, Shubina A, Arnulf B, Kropff M, Cavet J, Esseltine DL, Feng H, Girgis S, van de Velde H, Deraedt W, Harousseau JL.
This is a randomised, phase III study comparing efficacy and toxicity of bortezomib given IV (74 patients) vs SC (148 patients). Bortezomib was given to patients with relapsed myeloma, at a dose of 1.3 mg/m2 on days 1, 4, 8, 11 every 21 days, for a median of 8 cycles (range: 1-10).
SC injection were done reconstituting 3.5 mg with 1.4 mL NS (= 2.5 mg/mL). The drug was injected SC in the abdomen or the thighs, rotating the sites.
  - Response rate: 42% in both groups
  - Median time to progression: 9.4 months in the IV group and 10.4 months in the SC group (p= 0.39)
  - Overall survival at 1 year: 77% in the IV group and 73% in the SC group (p= 0·5)
  - Grade 3-4 adverse events: 70% in the SC group and 57% in the IV group (most commonly cytopenias)
  - Local reactions consisted of transient erythema
  - Peripheral neuropathy of any grade: 53% in the IV group and 38% in the SC group
  - Peripheral neuropathy of grade 3 or worse: 16% in the IV group and 6% in the SC group
The conclusion was that SC bortezomib had similar efficacy and decreased toxicity.

Consensus recommendations for the uniform reporting of clinical trials: report of the International Myeloma Workshop Consensus Panel 1.
Blood. 2011 May 5;117(18):4691-5.
Rajkumar SV, Harousseau JL, Durie B, Anderson KC, Dimopoulos M, Kyle R, Blade J, Richardson P, Orlowski R, Siegel D, Jagannath S, Facon T, Avet-Loiseau H, Lonial S, Palumbo A, Zonder J, Ludwig H, Vesole D, Sezer O, Munshi NC, San Miguel J; International Myeloma Workshop Consensus Panel 1.


JUNE 2011

Tanespimycin and bortezomib combination treatment in patients with relapsed or relapsed and refractory multiple myeloma: results of a phase 1/2 study.
Br J Haematol. 2011 Jun;153(6):729-40.
Richardson PG, Chanan-Khan AA, Lonial S, Krishnan AY, Carroll MP, Alsina M, Albitar M, Berman D, Messina M, Anderson KC.
72 patients with relapsed/refractory myeloma were treated with tanespimycin, a HSP90 inhibitor, in combination with bortezomib. RR was 27% (12% minimal responses, 12% partial responses, and 3% complete responses).



Giampaolo Talamo, MD