Increased serum lactate dehydrongenase should be included among the variables that define very-high-risk multiple myeloma.
Clin Lymphoma Myeloma Leuk. 2011 Oct;11(5):409-13.
Gkotzamanidou M, Kastritis E, Gavriatopoulou MR, Nikitas N, Gika D, Mparmparousi D, Matsouka C, Terpos E, Dimopoulos MA.
High serum levels of lactate dehydrogenase (LDH) predict for inferior survival and add prognostic value to the ISS. Analyzed of 203 patients found that median overall survival was 54 months in patients with normal LDH, and 21 months in patients with increased LDH. Increased LDH identified subgroups of patients within the ISS II and III stages with worse outcome.

Donor KIR haplotype B improves progression-free and overall survival after allogeneic hematopoietic stem cell transplantation for multiple myeloma.
Leukemia. 2011 Oct;25(10):1657-61.
Kröger N, Zabelina T, Berger J, Duske H, Klyuchnikov E, Binder T, Stübig T, Hilde-brandt Y, Atanackovic D, Alchalby H, Ayuk F, Zander AR, Bacher U, Eiermann T.
This study showed that allogeneic transplants from a donor carrying the B haplotype (BB or B/X), regardless of patient haplotype, had better clinical outcomes that transplant from donors with KIR haplotype AA. These findings are similar to those observed in patients with acute myeloblastic leukemia. KIR haplotype did not affect rates of acute and chronic GVHD. A sex-specific graft-vs-myeloma effect was observed with female donors, but allogeneic transplants with female donors was associated with a higher non-relapse mortality. The authors concluded that the donor of choice for myeloma patients undergoing an allogeneic stem cell transplantation should be a male carrying the KIR haplotype B. The use of female donors with the KIR haplotype AA was associated with impaired survival.

Ligand activation leads to regulated intramembrane proteolysis of fibroblast growth factor receptor 3.
Mol Biol Cell. 2011 Oct;22(20):3861-73.
Degnin CR, Laederich MB, Horton WA.



Prevalence of peripheral neuropathy in multiple myeloma at initial diagnosis.
Leuk Lymphoma. 2011 Nov;52(11):2135-8.
Malhotra P, Choudhary PP, Lal V, Varma N, Suri V, Varma S.
These authors performed electrophysiological studies in 29 patients with newly diagnosed myeloma, before treatment. 18 (62%) were found to have peripheral neuropathy, usually in the form of a sensory-motor axonal neuropathy.

Perifosine plus bortezomib and dexamethasone in patients with relapsed/refractory multiple myeloma previously treated with bortezomib: results of a multicenter phase I/II trial.
J Clin Oncol. 2011 Nov 10;29(32):4243-9.
Richardson PG, Wolf J, Jakubowiak A, Zonder J, Lonial S, Irwin D, Densmore J, Krishnan A, Raje N, Bar M, Martin T, Schlossman R, Ghobrial IM, Munshi N, Laubach J, Allerton J, Hideshima T, Colson K, Poradosu E, Gardner L, Sportelli P, Anderson KC.
Perifosine is an alkylphospholipid that inhibits both Akt and PI3K. In this study, 84 patients with relapsed/refractory myeloma were treated with perifosine 50 mg/day + bortezomib, with or without dexamethasone. Response rate was 41%, and median progression-free survival was 6.4 months.

Cereblon expression is required for the antimyeloma activity of lenalidomide and pomalidomide.
Blood. 2011 Nov 3;118(18):4771-9.
Zhu YX, Braggio E, Shi CX, Bruins LA, Schmidt JE, Van Wier S, Chang XB, Bjorklund CC, Fonseca R, Bergsagel PL, Orlowski RZ, Stewart AK.



A high rate of durable responses with romidepsin, bortezomib, and dexamethasone in relapsed or refractory multiple myeloma.
Blood. 2011 Dec 8;118(24):6274-83.
Harrison SJ, Quach H, Link E, Seymour JF, Ritchie DS, Ruell S, Dean J, Januszewicz H, Johnstone R, Neeson P, Dickinson M, Nichols J, Prince HM.
Among 25 patients with relapsed/refractory myeloma, the combination of bortezomib, dexamethasone, and romidepsine produced a response rate of 72% and a median time to progression of about 7 months. Of note, only 24% of patients were previously treated with a bortezomib-containing regimen.

Autologous haemopoietic stem-cell transplantation followed by allogeneic or autologous haemopoietic stem-cell transplantation in patients with multiple myeloma (BMT CTN 0102): a phase 3 biological assignment trial.
Lancet Oncol. 2011 Dec;12(13):1195-1203.
Krishnan A, Pasquini MC, Logan B, Stadtmauer EA, Vesole DH, Alyea E 3rd, Antin JH, Comenzo R, Goodman S, Hari P, Laport G, Qazilbash MH, Rowley S, Sahebi F, Somlo G, Vogl DT, Weisdorf D, Ewell M, Wu J, Geller NL, Horowitz MM, Giralt S, Maloney DG; on behalf of the Blood Marrow Transplant Clinical Trials Network (BMT CTN).
This is a phase III trial that randomized 625 patients with standard-risk myeloma (age <70) into two groups: one received tandem autologous transplants (366 evaluable patients), and the other received an autologous transplant followed by a mini-allogeneic transplant, if an HLA-matched sibling donor was available (156 evaluable patients). Patients of the auto-auto group were also randomized to maintenance with dexamethasone and thalidomide (219 patients, but only 77% completed it) vs observation (217 patients).
  - The 3-year progression-free survival was 46% in the auto-auto group, and 43% in the auto-allo group (p=0.67)
  - The 3-year overall survival was 80% in the auto-auto group, and 77% in the auto-allo group (p=0.19)
  - More than half of patients of the auto-allo group developed chronic GVHD
  - Progression-free survival and overall survival did not differ between the group receiving maintenance and the group followed with observation
The conclusion is that the auto-allo transplant strategy is not superior to the auto-auto one for standard-risk myeloma.

Similar efficacy of thalidomide- and bortezomib-based regimens for first relapse of multiple myeloma.
Ann Hematol. 2011 Dec;90(12):1441-7.
Krejci M, Gregora E, Straub J, Minarik J, Scudla V, Adam Z, Krivanova A, Pour L, Zahradova L, Buchler T, Mayer J, Hajek R.
A retrospective comparison between 105 patients treated with thalidomide-based regimens and 106 patients treated with bortezomib-based regimens found no significantly different clinical outcomes:
  - Response rate: 51% in the thalidomide group, and 50% in the bortezomib group (p= 0.77)
  - Median time to progression: 13 months in the thalidomide group, and 17 months in the bortezomib group (p= 0.21)
  - Median overall survival: 30 months in the thalidomide group, and 37 months in the bortezomib group (p= 0.89)

Lower incidence of plasma cell neoplasm is maintained in migrant Chinese to British Columbia: findings from a 30-year survey.
Leuk Lymphoma. 2011 Dec;52(12):2316-20.
Chan V, Song K, Mang O, Ip DK, Au WY.
In order to determine the importance of genetic vs environmental factors in the development of multiple myeloma, these authors reviewed the incidence of myeloma in patients of Chinese ethnicity who lived in British Columbia. They found these patients had the same incidence of myeloma of the Chinese population living in Hong Kong (1.6-1.8/100,000), but lower than the non-Chinese population of British Columbia. These findings suggest that genetic factors are more important than environmental factors in the development of multiple myeloma.

Personal and family history of immune-related conditions increase the risk of plasma cell disorders: a population-based study.
Blood. 2011 Dec 8;118(24):6284-91.
Lindqvist EK, Goldin LR, Landgren O, Blimark C, Mellqvist UH, Turesson I, Wahlin A, Björkholm M, Kristinsson SY.

Prognostic relevance of 18-F FDG PET/CT in newly diagnosed multiple myeloma patients treated with up-front autologous transplantation.
Blood. 2011 Dec 1;118(23):5989-95.
Zamagni E, Patriarca F, Nanni C, Zannetti B, Englaro E, Pezzi A, Tacchetti P, Buttignol S, Perrone G, Brioli A, Pantani L, Terragna C, Carobolante F, Baccarani M, Fanin R, Fanti S, Cavo M.
This study analyzed the prognostic relevance of PET in 192 patients with multiple myeloma. At multivariate analysis, independent variables for poor prognosis were:
  - SUV >4.2 at baseline (46%)
  - EMD at baseline (6%)
  - Persistent uptake after autologous stem cell transplant (35%)

Bendamustine in combination with thalidomide and dexamethasone is an effective therapy for myeloma patients with end stage renal disease.
Br J Haematol. 2011 Dec;155(5):632-4.
Ramasamy K, Hazel B, Mahmood S, Corderoy S, Schey S.
The authors treated 9 myeloma patients with the combination bendamustine-thalidomide-dexamethasone. Interestingly, 4 patients were on hemodialysis, and they did not require dose reduction. This is presumably due to the limited renal excretion of bendamustine.



Giampaolo Talamo, MD