JULY 2010

High incidence of arterial thrombosis in young patients treated for multiple myeloma: results of a prospective cohort study.
Blood. 2010 Jul 8;116(1):22-6.
Libourel EJ, Sonneveld P, van der Holt B, de Maat MP, Leebeek FW.
Among 195 patients with multiple myeloma, 11 (6%) developed arterial thrombosis. Most cases were seen during induction chemotherapy.

Histone deacetylases are critical targets of bortezomib-induced cytotoxicity in multiple myeloma.
Blood. 2010 Jul 22;116(3):406-17.
Kikuchi J, Wada T, Shimizu R, Izumi T, Akutsu M, Mitsunaga K, Noborio-Hatano K, Nobuyoshi M, Ozawa K, Kano Y, Furukawa Y.

Single agent lenalidomide in newly diagnosed multiple myeloma: a retrospective analysis.
Leuk Lymphoma. 2010 Jun;51(6):1015-9.
Baz R, Patel M, Finley-Oliver E, Lebovic D, Hussein MA, Miller KC, Wood M, Sher T, Lee K, Chanan-Khan AA.
A retrospective analysis of 17 patients with newly diagnosed myeloma treated with single agent lenalidomide showed a response rate of 47%.

Bortezomib, dexamethasone, cyclophosphamide and lenalidomide combination for newly diagnosed multiple myeloma: phase 1 results from the multicenter EVOLUTION study.
Leukemia. 2010 Jul;24(7):1350-6.
Kumar SK, Flinn I, Noga SJ, Hari P, Rifkin R, Callander N, Bhandari M, Wolf JL, Gasparetto C, Krishnan A, Grosman D, Glass J, Sahovic EA, Shi H, Webb IJ, Richardson PG, Rajkumar SV.
The addition of cyclophosphamide to VRD in 25 patients with newly diagnosed myeloma led to a response rate of 96% (68% with at least a very good partial response), but 3 patients (12%) experienced neutropenic fever, which usually requires hospital admission.



Comparison of serum immunofixation electrophoresis and free light chain assays in the detection of monoclonal gammopathies.
Clin Lymphoma Myeloma Leuk. 2010 Aug 1;10(4):278-80.
Wood PB, McElroy YG, Stone MJ.

Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma.
Blood. 2010 Aug 5;116(5):679-86.
Richardson PG, Weller E, Lonial S, Jakubowiak AJ, Jagannath S, Raje NS, Avigan DE, Xie W, Ghobrial IM, Schlossman RL, Mazumder A, Munshi NC, Vesole DH, Joyce R, Kaufman JL, Doss D, Warren DL, Lunde LE, Kaster S, Delaney C, Hideshima T, Mitsiades CS, Knight R, Esseltine DL, Anderson KC.
This is a phase I/II study of VRD in 66 patients with newly diagnosed myeloma. MTD was found to be:
  - Bortezomib 1.3 mg/m2 IV on days 1, 4, 8, 11
  - Lenalidomide 25 mg PO qd on days 1-14
  - Dexamethasone 20 mg PO on days 1,2, 4,5, 8,9, 11,12
Cycles were repeated every 21 days.
  - Response rate was 100%. Complete remission: 57%. 74% of patients achieved VGPR or better.
  - Maximal response was often achieved after 4 cycles
  - Median collection yield was 5.6 million CD34+ cells/Kg (28 patients proceeded to stem cell transplant)
  - After a median follow-up of 21 months, estimated 18-month progression-free survival was 75%, and overall survival 97%.
  - Most common toxicities were peripheral neuropathy (80%) and fatigue (64%)
  - Painful sensory neuropathy: 32%
  - DVT rate was 6%
  - 40%  of patients required dose reductions, interruptions, or discontinuation of therapy because of toxicity

Reduced-intensity allogeneic hematopoietic stem cell transplantation for relapsed multiple myeloma.
Biol Blood Marrow Transplant. 2010 Aug;16(8):1122-9.
Efebera YA, Qureshi SR, Cole SM, Saliba R, Pelosini M, Patel RM, Koca E, Mendoza FL, Wang M, Shah J, Alousi A, Hosing C, Popat U, Kebriaei P, Anderlini P, Khouri IF, Champlin R, Giralt S, Qazilbash MH.
51 patients with relapsed myeloma underwent a RIC allogeneic SCT, using fludarabine 90-120 mg/m2 + melphalan 90-140 mg/m2. Results:
  - Transplant-related mortality at 100 days: 12%
  - Transplant-related mortality at 1 year: 25%
  - Grade II/IV acute GVHD: 27%
  - Grade II/IV chronic GVHD: 47%
  - Progression-free survival at 2 years: 19%
  - Overall survival at 2 years: 32%
  - Long-term survivors in remission (presumed cure): 14%
N.B.: These patients were heavily pretreated, with a predicted life expectancy of only 8-12 months.

Allogenic hematopoietic stem-cell transplantation with reduced-intensity conditioning in patients with refractory and recurrent multiple myeloma: long-term follow-up.
Cancer. 2010 Aug 1;116(15):3621-30.
Shimoni A, Hardan I, Ayuk F, Schilling G, Atanackovic D, Zeller W, Yerushalmi R, Zander AR, Kroger N, Nagler A.
This is a retrospective study of 50 patients with relapsed/refractory myeloma treated with RIC allogeneic SCT. Stem cells were taken from a sibling (27 patients) or matched unrelated donors (23 patients). At a median follow-up of 6.4 years, progression-free survival was 26%, and overall survival 34%. Non-relapse mortality was 26%.

Primary therapy with single agent bortezomib as induction, maintenance and re-induction in patients with high-risk myeloma: results of the ECOG E2A02 trial.
Leukemia. 2010 Aug;24(8):1406-11.
Dispenzieri A, Jacobus S, Vesole DH, Callandar N, Fonseca R, Greipp PR.
At the time of this publications, many myeloma experts believed that bortezomib overcame the negative impact of adverse cytogenetics in multiple myeloma. This study utilized bortezomib as primary therapy (i.e., induction x8 cycles, maintenance with 1 dose every other week, indefinitely, and salvage therapy - without stem cell transplantation) in patients with high-risk myeloma. Results:
  - Response rate: 48%
  - Median progression-free survival: 8 months (95% CI 6-12 months)
  - Overall survival at 1 year: 88%
  - Overall survival at 2 years: 76%



Kidney disease associated with plasma cell dyscrasias.
Blood. 2010 Sep 2;116(9):1397-404.
Heher EC, Goes NB, Spitzer TR, Raje NS, Humphreys BD, Anderson KC, Richardson PG.

Melphalan and prednisone plus thalidomide or placebo in elderly patients with multiple myeloma.
Blood. 2010 Sep 2;116(9):1405-12.
Waage A, Gimsing P, Fayers P, Abildgaard N, Ahlberg L, Björkstrand B, Carlson K, Dahl IM, Forsberg K, Gulbrandsen N, Haukås E, Hjertner O, Hjorth M, Karlsson T, Knudsen LM, Nielsen JL, Linder O, Mellqvist UH, Nesthus I, Rolke J, Strandberg M, Sørbø JH, Wisløff F, Juliusson G, Turesson I; Nordic Myeloma Study Group.
This is a double-blind study of 363 patients with newly diagnosed myeloma, randomized to receive MPT (melphalan 0.25 mg/Kg + prednisone 100 mg days 1-4 every 6 weeks, and thalidomide 100-400 mg PO qhs) vs MP + placebo. Results:
  - Partial response was 34% with MPT and 33% with MP
  - VGPR or better was 23% with MPT and 7% with MP (p <0.001)
  - No difference in progression-free survival: 15 months with MPT and 14 months with MP (p= 0.16)
  - No difference in overall survival: 29 months with MPT and 32 months with MP (p= 0.16)

Clarithromycin (Biaxin)-lenalidomide-low-dose dexamethasone (BiRd) versus lenalidomide-low-dose dexamethasone (Rd) for newly diagnosed myeloma.
Am J Hematol. 2010 Sep;85(9):664-9.
Gay F, Rajkumar SV, Coleman M, Kumar S, Mark T, Dispenzieri A, Pearse R, Gertz MA, Leonard J, Lacy MQ, Chen-Kiang S, Roy V, Jayabalan DS, Lust JA, Witzig TE, Fonseca R, Kyle RA, Greipp PR, Stewart AK, Niesvizky R.
This is a case-matched study of 72 patients with newly diagnosed myeloma, treated with BiRd or Rd. The retrospective analysis favored BiRd:
  - Rate of complete response: 46% with BiRd and 14% with Rd (p <0.001)
  - Median progression-free survival: 48.3 months with BiRd and 27.5 months with Rd (p= 0.044)
  - Overall survival at 3 years: 90% with BiRd and 73% with Rd (only trend: p 0.17)



Giampaolo Talamo, MD