JANUARY 2011

Vaccination with dendritic cell/tumor fusion cells results in cellular and humoral antitumor immune responses in patients with multiple myeloma.
Blood. 2011 Jan 13;117(2):393-402.
Rosenblatt J, Vasir B, Uhl L, Blotta S, Macnamara C, Somaiya P, Wu Z, Joyce R, Levine JD, Dombagoda D, Yuan YE, Francoeur K, Fitzgerald D, Richardson P, Weller E, Anderson K, Kufe D, Munshi N, Avigan D.
15 patients with myeloma were treated with a tumor vaccine consisting of their dendritic cells chemically fused with their myeloma cells. Several patients with advanced disease experienced disease stabilization (41 months in one patient).

Chemomobilization with Etoposide is Highly Effective in Patients with Multiple Myeloma and Overcomes the Effects of Age and Prior Therapy.
Biol Blood Marrow Transplant. 2011 Jan;17(1):141-6.
Wood WA, Whitley J, Moore D, Sharf A, Irons R, Rao K, Serody J, Coghill J, Gabriel D, Shea T.
152 patients received etoposide 375 mg/m2 on days 1 and 2, followed by G-CSF 5 mcg/Kg twice daily from day 3. Mobilization was successful in 100% of cases, and 94% of patients collected in a single day. Median number of CD34+ cells/Kg was 12 × 10(6).

Phase 2 trial of the histone deacetylase inhibitor romidepsin for the treatment of refractory multiple myeloma.
Cancer. 2011 Jan 15;117(2):336-42.
Niesvizky R, Ely S, Mark T, Aggarwal S, Gabrilove JL, Wright JJ, Chen-Kiang S, Sparano JA.
This is a phase 2 trial of romidepsin in 12 patients with multiple myeloma.  Four of 12 patients had stable disease, but no patients had an objective response.

Pegfilgrastim reduces the length of hospitalization and the time to engraftment in multiple myeloma patients treated with melphalan 200 and auto-SCT compared with filgrastim.
Ann Hematol. 2011 Jan;90(1):89-94.
Samaras P, Blickenstorfer M, Siciliano RD, Haile SR, Buset EM, Petrausch U, Mischo A, Honegger H, Schanz U, Stussi G, Stahel RA, Knuth A, Stenner-Liewen F, Renner C.
This is a retrospective comparison of filgrastim (46 patients) vs pegfilgrastim (46 patients) after melphalan 200 mg/m2. results:
  - Median duration of grade 4 neutropenia: 6 days with filgrastim and 5 days with pegfilgrastim (p=0.008)
  - Median duration of hospitalization: 15.5 days with filgrastim and 14.5 days with pegfilgrastim (p=0.024)
  - Cost was reduced with the use of peg-filgrastim

Asymptomatic immunoglobulin light chain amyloidosis (AL) at the time of diagnostic bone marrow biopsy in newly diagnosed patients with multiple myeloma and smoldering myeloma. A series of 144 cases and a review of the literature.
Ann Hematol. 2011 Jan;90(1):101-6.
Siragusa S, Morice W, Gertz MA, Kyle RA, Greipp PR, Lust JA, Witzig TE, Lacy MQ, Zeldenrust SR, Rajkumar SV, Russell SJ, Hayman SR, Buadi F, Kumar SK, Dingli D, Dispenzieri A.
Among 144 bone marrow biopsies of patients with multiple myeloma (67 with smoldering myeloma), amyloid was detected in only 2 cases (1%), and none had clinical manifestations suggestive of amyloidosis. Only 1 of 142 patients without amyloid deposition in the bone marrow developed symptomatic amyloidosis during the course of his disease (after 119 months).

Thalidomide after lenalidomide: a possible treatment regimen in relapse refractory multiple myeloma patients.
Br J Haematol. 2011 Jan;152(1):108-10.
Guglielmelli T, Petrucci MT, Saglio G, Palumbo A.
Among 14 patients treated with thalidomide + dexamethasone, after previous exposure to lenalidomide, response rate was 14% (2 patients). Progressive disease was seen in 3 patients, and minor responses/stable disease in 9 (64%).

 

FEBRUARY 2011

Translocation t(14;16) and multiple myeloma: is it really an independent prognostic factor?
Blood. 2011 Feb 10;117(6):2009-11.
Avet-Loiseau H, Malard F, Campion L, Magrangeas F, Sebban C, Lioure B, Decaux O, Lamy T, Legros L, Fuzibet JG, Michallet M, Corront B, Lenain P, Hulin C, Mathiot C, Attal M, Facon T, Harousseau JL, Minvielle S, Moreau P; Intergroupe Francophone du Myélome.
This study is a retrospective analysis of 32 patients with t(14;16), found among 1003 patients with newly diagnosed myeloma (3%). Patients with t(14;16) had an overall survival similar to that of patients without the translocation.

Tandem autologous non-myeloablative allogeneic transplantation in patients with multiple myeloma relapsing after a first high dose therapy.
Bone Marrow Transplant. 2011 Feb;46(2):250-6.
Karlin L, Arnulf B, Chevret S, Ades L, Robin M, De Latour RP, Malphettes M, Kabbara N, Asli B, Rocha V, Fermand JP, Socie G.
This is a retrospective study of 23 patients with myeloma in relapse after an autologous stem cell transplant. Patients received salvage tandem transplants, with an autologous SCT followed by a mini-allogeneic SCT. Results:
  - Median event-free survival 36.8 months
  - Median overall survival: 60 months
  - Overall survival at 2 years: 61%
Compared with patients who did not receive allogeneic SCT, these patients had a significant survival advantage.

Clinical and biological features of t(4;14) multiple myeloma: a prospective study.
Leuk Lymphoma. 2011 Feb;52(2):238-46.
Karlin L, Soulier J, Chandesris O, Choquet S, Belhadj K, Macro M, Bouscary D, Porcher R, Ghez D, Malphettes M, Asli B, Brouet JC, Bories JC, Hermine O, Fermand JP, Arnulf B.
This is a report of 102 consecutive patients with myeloma expressing the t(4;14). Prognosis was poor, with median progression-free survival of 12 months, and median overall survival after transplantation of 31 months.

Immunoglobulin D multiple myeloma: response to therapy, survival, and prognostic factors in 75 patients.
Ann Oncol. 2011 Feb;22(2):411-6.
Kim MK, Suh C, Lee DH, Min CK, Kim SJ, Kim K, Moon JH, Yoon SS, Lee GW, Kang HJ, Kim SH, Choi CW, Eom HS, Kwak JY, Kim HJ, Mun YC, Bang SM, Lee K, Shin HJ, Lee JH; Korean Multiple Myeloma Working Party.
This is a retrospective analysis of 75 patients with IgD myeloma. Renal insufficiency was present in 53% of them, and hypercalcemia in 27%. Prognosis was relatively poor. At a median follow-up of 29 months, median overall survival was 18.5 months.

 

MARCH 2011

Randomized, double-blind study of denosumab versus zoledronic Acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma.
J Clin Oncol. 2011 Mar 20;29(9):1125-32.
Henry DH, Costa L, Goldwasser F, Hirsh V, Hungria V, Prausova J, Scagliotti GV, Sleeboom H, Spencer A, Vadhan-Raj S, von Moos R, Willenbacher W, Woll PJ, Wang J, Jiang Q, Jun S, Dansey R, Yeh H.
This study randomized patients to receive either zoledronic acid 4 mg IV or denosumab 120 mg SC for bone metastases. It included patients with multiple myeloma: 93 in the zoledronic acid arm, and 87 in the denosumab arm. For the entire study population, the median time to development of a skeletal-related event was 16.3 months with zoledronic acid and 20.6 with denosumab. No difference in progression-free survival or overall survival was observed, but a more favorable survival was observed in patients with multiple myeloma receiving zoledronic acid (HR: 2.26, 95% CI: 1.13-4.5). Osteonecrosis of the jaw occurred rarely in both groups (about 1%).

Complete response correlates with long-term progression-free and overall survival in elderly myeloma treated with novel agents: analysis of 1175 patients.
Blood. 2011 Mar 17;117(11):3025-31.
Gay F, Larocca A, Wijermans P, Cavallo F, Rossi D, Schaafsma R, Genuardi M, Romano A, Liberati AM, Siniscalchi A, Petrucci MT, Nozzoli C, Patriarca F, Offidani M, Ria R, Omedè P, Bruno B, Passera R, Musto P, Boccadoro M, Sonneveld P, Palumbo A.
This is a retrospective analysis of 1175 patients with newly diagnosed myeloma enrolled in multicenter clinical trials, after a median follow-up of 29 months.
  - PFS at 3 years: 67% in patients who achieved CR, and 27% in patients who achieved VGPR
  - OS at 3 years: 91% in patients who achieved CR, and 70% in patients who achieved VGPR

Plerixafor (Mozobil) for stem cell mobilization in patients with multiple myeloma previously treated with lenalidomide.
Bone Marrow Transplant. 2011 Mar;46(3):350-5.
Micallef IN, Ho AD, Klein LM, Marulkar S, Gandhi PJ, McSweeney PA.

Aspirin, Warfarin, or Enoxaparin Thromboprophylaxis in Patients With Multiple Myeloma Treated With Thalidomide: A Phase III, Open-Label, Randomized Trial.
J Clin Oncol. 2011 Mar 10;29(8):986-93.
Palumbo A, Cavo M, Bringhen S, Zamagni E, Romano A, Patriarca F, Rossi D, Gentilini F, Crippa C, Galli M, Nozzoli C, Ria R, Marasca R, Montefusco V, Baldini L, Elice F, Callea V, Pulini S, Carella AM, Zambello R, Benevolo G, Magarotto V, Tacchetti P, Pescosta N, Cellini C, Polloni C, Evangelista A, Caravita T, Morabito F, Offidani M, Tosi P, Boccadoro M.
In this study, 667 patients with myeloma treated with thalidomide were randomized into 3 groups:
  - Aspirin 100 mg/day PO
  - Warfarin fixed low-dose, 1.25 mg/day PO
  - LMWH: enoxaparin 40 mg/day SC
Treatment was continued for the first 3-6 cycles of induction therapy. Both aspirin and fixed low-dose warfarin showed similar efficacy in reducing thromboembolic complications when compared with LMWH. Rate of complications (i.e., DVT, PE, arterial thrombosis, acute cardiovascular events, and sudden death) was:
  - 5% with LMWH
  - 6% with aspirin
  - 8% with warfarin

Weekly bortezomib in combination with temsirolimus in relapsed or relapsed and refractory multiple myeloma: a multicentre, phase 1/2, open-label, dose-escalation study.
Lancet Oncol. 2011 Mar;12(3):263-72.
Ghobrial IM, Weller E, Vij R, Munshi NC, Banwait R, Bagshaw M, Schlossman R, Leduc R, Chuma S, Kunsman J, Laubach J, Jakubowiak AJ, Maiso P, Roccaro A, Armand P, Dollard A, Warren D, Harris B, Poon T, Sam A, Rodig S, Anderson KC, Richardson PG.
A total of 63 patients with relapsed/refractory myeloma were treated with bortezomib and temsirolimus. In the phase II portion of the study (43 patients), response rate was 33%.

Initial genome sequencing and analysis of multiple myeloma.
Nature. 2011 Mar 24;471(7339):467-72.
Chapman MA, Lawrence MS, Keats JJ, Cibulskis K, Sougnez C, Schinzel AC, Harview CL, Brunet JP, Ahmann GJ, Adli M, Anderson KC, Ardlie KG, Auclair D, Baker A, Bergsagel PL, Bernstein BE, Drier Y, Fonseca R, Gabriel SB, Hofmeister CC, Jagannath S, Jakubowiak AJ, Krishnan A, Levy J, Liefeld T, Lonial S, Mahan S, Mfuko B, Monti S, Perkins LM, Onofrio R, Pugh TJ, Rajkumar SV, Ramos AH, Siegel DS, Sivachenko A, Stewart AK, Trudel S, Vij R, Voet D, Winckler W, Zimmerman T, Carpten J, Trent J, Hahn WC, Garraway LA, Meyerson M, Lander ES, Getz G, Golub TR.

 

 


Giampaolo Talamo, MD