JULY 2012

Intermediate-Dose versus Low-Dose Cyclophosphamide and Granulocyte Colony-Stimulating Factor for Peripheral Blood Stem Cell Mobilization in Patients with Multiple Myeloma Treated with Novel Induction Therapies.
Biol Blood Marrow Transplant. 2012 Jul;18(7):1128-35.
Hamadani M, Kochuparambil ST, Osman S, Cumpston A, Leadmon S, Bunner P, Watkins K, Morrison D, Speir E, Deremer D, Kota V, Jillella A, Craig M, Awan F.
This study compares outcomes of stem cell collections in 123 myeloma patients who underwent the collection within 1 year of starting therapy with novel agents. Mobilization regimen was:
  - Low-dose cyclophosphamide, 1.5/m2 + G-CSF (68 patients)
  - Intermediate-dose cyclophosphamide, 3-4 g/m2 + G-CSF (55 patients)
Stem cell yield was superior in patients who received intermediate-dose cyclophosphamide (16.6 vs 7.5 million CD34+ cells/Kg).

No association between cigarette smoking and incidence of plasma cell myeloma: A meta-analysis of 17 observational studies.
Am J Hematol. 2012 Jul;87(7):729-31.
Castillo JJ, Dhami PK, Curry S, Brennan K.

Bortezomib-thalidomide-dexamethasone is superior to thalidomide-dexamethasone as consolidation therapy after autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma.
Blood. 2012 Jul 5;120(1):9-19.
Cavo M, Pantani L, Petrucci MT, Patriarca F, Zamagni E, Donnarumma D, Crippa C, Boccadoro M, Perrone G, Falcone A, Nozzoli C, Zambello R, Masini L, Furlan A, Brioli A, Derudas D, Ballanti S, Dessanti ML, De Stefano V, Carella AM, Marcatti M, Nozza A, Ferrara F, Callea V, Califano C, Pezzi A, Baraldi A, Grasso M, Musto P, Palumbo A; for the GIMEMA (Gruppo Italiano Malattie Ematologiche dell'Adulto) Italian Myeloma Network.
This is a phase 3 study which randomized patients with newly diagnosed myeloma treated with tandem autologous transplants into 2 groups:
  - TD group (161 patients) : Thalidomide and Dexamethasone during induction and maintenance therapy
  - VTD group (160 patients): Bortezomib, Thalidomide, and Dexamethasone during induction and maintenance therapy
Patients treated with VTD has better outcomes:
  - CR/nCR rate was 61% with TD and 73% with VDT
  - Progression-free survival at 3 years was 48% with TD and 60% with VDT
  - Overall survival was similar, but this could be due to short follow-up (median follow-up was 30 months), or to the effect of different salvage therapies

A phase 2 study of pegylated liposomal doxorubicin, bortezomib, dexamethasone and lenalidomide for patients with relapsed/refractory multiple myeloma.
Leukemia. 2012 Jul;26(7):1675-80.
Berenson JR, Yellin O, Kazamel T, Hilger JD, Chen CS, Cartmell A, Woliver T, Flam M, Bravin E, Nassir Y, Vescio R, Swift RA.
This is a phase II trial of 40 patients with relapsed/refractory myeloma patients, treated with:
  - Bortezomib 1.0 mg/m2 IV on days 1, 4, 8, 11
  - Liposomal doxorubicin 4 mg/m2 IV on days 1, 4, 8, 11
  - Dexamethasone 40 mg on days 1, 4, 8, 11
  - Lenalidomide 10 mg on days 1-14
Cycles were repeated every 28 days.
Clinical benefit was about 85%: Minimal response 36%, PR 18%, VGPR 10%, CR 20%.

Superiority of the Triple Combination of Bortezomib-Thalidomide-Dexamethasone Over the Dual Combination of Thalidomide-Dexamethasone in Patients With Multiple Myeloma Progressing or Relapsing After Autologous Transplantation: The MMVAR/IFM 2005-04 Randomized Phase III Trial From the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation.
J Clin Oncol. 2012 Jul 10;30(20):2475-82.
Garderet L, Iacobelli S, Moreau P, Dib M, Lafon I, Niederwieser D, Masszi T, Fontan J, Michallet M, Gratwohl A, Milone G, Doyen C, Pegourie B, Hajek R, Casassus P, Kolb B, Chaleteix C, Hertenstein B, Onida F, Ludwig H, Ketterer N, Koenecke C, van Os M, Mohty M, Cakana A, Gorin NC, de Witte T, Harousseau JL, Morris C, Gahrton G.
The triple combination Bortezomib + Thalidomide + Dexamethasone (VTD) was superior to Thalidomide + Dexamethasone (TD) in 296 patients with myeloma relapsing after autologous stem cell transplantation:
  - Rate of CR/nCR: 45% with VTD and 25% with TD
  - Median progression-free survival was 19.5 months with VTD and 13.8 months with TD
  - 2-year survival: 71% with VTD and 65% with TD
The editorial article accompanying this study underscores the fact that these results are the best seen among all phase III studies for refractory myeloma, because the progression-free survival of all previously published studies was less than 12 months.



Effect of time to infusion of autologous stem cells (24 vs. 48 h) after high-dose melphalan in patients with multiple myeloma.
Eur J Haematol, 2012; 89(2):145-50.
Talamo G.
, Rakszawski K.L., Rybka W.B., Dolloff N.G., Malysz J., Berno T., Zangari M.

A phase 1/2 study of carfilzomib in combination with lenalidomide and low-dose dexamethasone as a frontline treatment for multiple myeloma.
Blood. 2012 Aug 30;120(9):1801-9.
Jakubowiak AJ, Dytfeld D, Griffith KA, Lebovic D, Vesole DH, Jagannath S, Al-Zoubi A, Anderson T, Nordgren B, Detweiler-Short K, Stockerl-Goldstein K, Ahmed A, Jobkar T, Durecki DE, McDonnell K, Mietzel M, Couriel D, Kaminski M, Vij R.
In this study, 53 patients with newly diagnosed myeloma were treated with CRD:
  - Carfilzomib 20-36 mg/m2 IV on days 1,2, 8,9, 15,16 (1,2, 15,16 after cycle 8)
  - Revlimid 25 mg PO on days 1-21
  - Dexamethasone 20-40 mg PO once a week
Cycles were repeated every 28 days. 36 patients underwent stem cell transplantation. Median follow-up was 13 months.
Results: at least nCR 62%, stringent CR 42%. Progression-free survival at 2 years was 92%.

Bortezomib Induction and Maintenance Treatment in Patients With Newly Diagnosed Multiple Myeloma: Results of the Randomized Phase III HOVON-65/ GMMG-HD4 Trial.
J Clin Oncol. 2012 Aug 20;30(24):2946-55.
Sonneveld P, Schmidt-Wolf IG, van der Holt B, El Jarari L, Bertsch U, Salwender H, Zweegman S, Vellenga E, Broyl A, Blau IW, Weisel KC, Wittebol S, Bos GM, Stevens-Kroef M, Scheid C, Pfreundschuh M, Hose D, Jauch A, van der Velde H, Raymakers R, Schaafsma MR, Kersten MJ, van Marwijk-Kooy M, Duehrsen U, Lindemann W, Wijermans PW, Lokhorst HM, Goldschmidt HM.
827 patients with newly diagnosed myeloma were randomized to:
  - VAD (vincristine, doxorubicin, dexamethasone), autologous transplant, maintenance with thalidomide 50 mg daily (group A)
  - PAD (bortezomib, doxorubicin, dexamethasone), autologous transplant, maintenance with PAD every 2 weeks for 2 years
Progression-free survival was 28 months in group A and 35 months in group B.
In patients with 17p-, PFS was 12 months in group A and 22 months in group B.



Phase II trial of the pan-deacetylase inhibitor panobinostat as a single agent in advanced relapsed/refractory multiple myeloma.
Leuk Lymphoma. 2012 Sep;53(9):1820-3.
Wolf JL, Siegel D, Goldschmidt H, Hazell K, Bourquelot PM, Bengoudifa BR, Matous J, Vij R, de Magalhaes-Silverman M, Abonour R, Anderson KC, Lonial S.
Only 1 partial response was observed among 38 patients treated with panobinostat.

An open-label, single-arm, phase 2 study of single-agent carfilzomib in patients with relapsed and/or refractory multiple myeloma who have been previously treated with bortezomib.
Br J Haematol. 2012 Sep;158(6):739-48.
Vij R, Siegel DS, Jagannath S, Jakubowiak AJ, Stewart AK, McDonagh K, Bahlis N, Belch A, Kunkel LA, Wear S, Wong AF, Wang M.
SourceWashington University School of Medicine, St. Louis, MO, USA.
In 35 patients previously treated with a bortezomib-based regimen, carfilzomib induced a response rate of 17%. Median time to progression was 4.6 months. Peripheral neuropathy did not exacerbate with carfilzomib.

How I treat plasma cell leukemia.
Blood. 2012 Sep 20;120(12):2376-89.
van de Donk NW, Lokhorst HM, Anderson KC, Richardson PG.
This publication proposed response criteria for PCL.

Phase II study of melphalan, thalidomide and prednisone combined with oral panobinostat in patients with relapsed/refractory multiple myeloma.
Leuk Lymphoma. 2012 Sep;53(9):1722-7.
Offidani M, Polloni C, Cavallo F, Liberati AM, Ballanti S, Pulini S, Catarini M, Alesiani F, Corvatta L, Gentili S, Caraffa P, Boccadoro M, Leoni P, Palumbo A.
Response rate of MPT + panobinostat in relapsed/refractory myeloma was 38%.

FDG PET or PET/CT for Detecting Intramedullary and Extramedullary Lesions in Multiple Myeloma: A Systematic Review and Meta-analysis.
Clin Nucl Med. 2012 Sep;37(9):833-7.
Lu YY, Chen JH, Lin WY, Liang JA, Wang HY, Tsai SC, Kao CH.
This is a review of 14 studies with 395 patients with multiple myeloma.
The pooled estimates of sensitivity of PET were: 61% for intramedullary lesions and 96% for extramedullary lesions.
The pooled estimates of specificity of PET were: 94% for intramedullary lesions and 78% for extramedullary lesions.



Giampaolo Talamo, MD