APRIL 2015

Varicella zoster virus reactivation after autologous SCT is a frequent event and associated with favorable outcome in myeloma patients.
Bone Marrow Transplant. 2015 Apr;50(4):573-8.
Kamber C, Zimmerli S, Suter-Riniker F, Mueller BU, Taleghani BM, Betticher D, Zander T, Pabst T.
In this study, reactivation of the varicella zoster virus (VZV) developed in 57 (30%) of 191 patients with myeloma. The VZV reactivation occurred during the induction chemotherapy (8.5% of patients), or after the autologous stem cell transplant (ASCT) (21.5% of patients). Interestingly, for unclear reasons, there was an association between the VZV reactivation after the ASCT and a better median overall survival ("not reached" vs 87 months). Patients received acyclovir 400 mg twice a day for 3 weeks after the ASCT. The incidence of VZV reactivation after the ASCT was about 10% at 1 year, about 15% at 2 years, and about 20% at 4 years.

Phase Ib/II trial of CYKLONE (cyclophosphamide, carfilzomib, thalidomide and dexamethasone) for newly diagnosed myeloma.
Br J Haematol. 2015 Apr;169(2):219-27.
Mikhael JR1, Reeder CB, Libby EN, Costa LJ, Bergsagel PL, Buadi F, Mayo A, Nagi Reddy SK, Gano K, Dueck AC, Stewart AK.

New cancers after autotransplantations for multiple myeloma.
Biol Blood Marrow Transplant. 2015 Apr;21(4):738-45.
Mahindra A1, Raval G, Mehta P, Brazauskas R, Zhang MJ, Zhong X, Bird JM, Freytes CO, Hale GA, Herzig R, Holmberg LA, Kamble RT, Kumar S, Lazarus HM, Majhail NS, Marks DI, Moreb JS, Olsson R, Saber W, Savani BN, Schiller GJ, Tay J, Vogl DT, Waller EK, Wiernik PH, Wirk B, Lonial S, Krishnan AY, Dispenzieri A, Brandenburg NA, Gale RP, Hari PN.
This study reviews incidence of second cancers among 4161 patients with multiple myeloma treated with an autologous stem cell transplant. Follow-up identified 163 cases of new cancers, with a cumulative incidence of 6.1% at 7 years after transplant. The incidence of new cancers in these patients was similar to that in matched U.S. population, with the exception of AML and melanoma, which were more frequent. Multivariate analysis showed that factors associated to an increased risk of second cancers were obesity, older age, and male gender.

APOBEC family mutational signatures are associated with poor prognosis translocations in multiple myeloma.
Nat Commun. 2015 Apr 23;6:6997.
Walker BA, Wardell CP, Murison A, Boyle EM, Begum DB, Dahir NM, Proszek PZ, Melchor L, Pawlyn C, Kaiser MF, Johnson DC, Qiang YW, Jones JR, Cairns DA, Gregory WM, Owen RG, Cook G, Drayson MT, Jackson GH, Davies FE, Morgan GJ.
The authors did whole exomic sequence of 463 cases of newly diagnosed multiple myeloma. They found an APOBEC mutational signature in 4% of cases. They were associated to the translocations t(14;16) and t(14;20), which result in deregulation of the MAF and MAFB genes, respectively. APOBEC is a family of enzymes editing the DNA, and they deaminate cytosine to uracil in single-stranded DNA.
  - In MAF and MAFB, the mutations were only seen in the basic-leucine zipper domain
  - In FGFR3, the mutations were scattered throughout the gene


MAY 2015

Development of acute pulmonary hypertension after bortezomib treatment in a patient with multiple myeloma: a case report and the review of the literature.
Am J Ther. 2015 May-Jun;22(3):e88-92.
Akosman C, Ordu C, Eroglu E, Oyan B.

Phase I/II study of the combination of panobinostat and carfilzomib in patients with relapsed/refractory multiple myeloma.
Haematologica. 2015 May;100(5):670-6.
Berdeja JG, Hart LL, Mace JR, Arrowsmith ER, Essell JH, Owera RS, Hainsworth JD, Flinn IW.
In this study, 44 patients with myeloma relapsed after at least one line of therapy were treated with carfilzomib + panobinostat. Optimal doses were 20/45 mg/m2 for carfilzomib, and 30 mg for panobinostat. The response rate was 67% for all patients. At a median follow up of 17 months, median overall survival was not reached, and median progression-free survival was 8 months.

Features of extramedullary disease of multiple myeloma: high frequency of p53 deletion and poor survival: a retrospective single-center study of 834 cases.
Clin Lymphoma Myeloma Leuk. 2015 May;15(5):286-91.
Deng S, Xu Y, An G, Sui W, Zou D, Zhao Y, Qi J, Li F, Hao M, Qiu L.
Among 834 consecutive MM patients in a single center in China, extrameduallary disease was found in 4.8% of cases at the time of diagnosis, and in 3.4% during the course of the disease. Patients with extrameduallary disease had a higher prevalence of p53 deletion at FISH (35% vs. 12%), worse time to progression (12 vs 25 months), and worse median survival (16.5 vs 40 months). At multivariate analysis, the presence of EMD remained an independent adverse prognostic factor.

Comparison of HevyliteÖ IgA and IgG assay with conventional techniques for the diagnosis and follow-up of plasma cell dyscrasia.
Ann Clin Biochem. 2015 May;52(Pt 3):337-45.
Paolini L, Di Noto G, Maffina F, Martellosio G, Radeghieri A, Luigi C, Ricotta D.

Phase 1/2 study of carfilzomib plus melphalan and prednisone in patients aged over 65 years with newly diagnosed multiple myeloma.
Blood. 2015 May 14;125(20):3100-4.
Moreau P, Kolb B, Attal M, Caillot D, Benboubker L, Tiab M, Touzeau C, Leleu X, Roussel M, Chaleteix C, Planche L, Chiffoleau A, Fortin J, Avet-Loiseau H, Mary JY, Hulin C, Facon T.
CMP (carfilzomib, melphalan, and prednisone) was administered for up to 9 cycles to 66 elderly patients with newly diagnosed myeloma (24 patients for phase 1 and 44 patients for phase 2). The MTD for carfilzomib was established as 36 mg/m2. Among 50 evaluable patients, the response rate was 90%, and the projected 3-year overall survival rate was 80%.


JUNE 2015

Comparison of upfront tandem autologous-allogeneic transplantation versus reduced intensity allogeneic transplantation for multiple myeloma.
Bone Marrow Transplant. 2015 Jun;50(6):802-7.
Sahebi F, Iacobelli S, Biezen AV, Volin L, Dreger P, Michallet M, Ljungman PT, de Witte T, Henseler A, Schaap NP, Lˇpez-Corral L, Poire X, Passweg J, Hamljadi RM, Thomas SH, Schonland S, Gahrton G, Morris C, KrÍger N, Garderet L.

This is a retrospective study comparing the outcomes of an early reduced intensity conditioning (RIC) allogeneic transplant (173 patients) vs tandem autologous-allogeneic transplant (517 patients). After a median follow-up of about 8 years, results favored the planned tandem auto-allo transplants:
   - 5-year progression-free survival: 22% in the allo group, and 34% in the auto-allo group (p<0.001)
   - 5-year overall survival: 42% in the allo group, and 59% in the auto-allo group (p<0.001)

Autologous stem cell transplantation versus novel drugs or conventional chemotherapy for patients with relapsed multiple myeloma after previous ASCT.
Bone Marrow Transplant. 2015 Jun;50(6):808-12.
Gr÷vdal M, Nahi H, Gahrton G, Liwing J, Waage A, Abildgaard N, Pedersen PT, Hammerstr°m J, Laaksonen A, Bazia P, Terava V, Ollikainen H, Silvennoinen R, Putkonen M, Anttila P, Porkka K, Remes K.
This is a retrospective analysis of outcomes between salvage therapies in patiuents with multiple myeloma in relapse after they already received a first autologous stem cell transplant. A second autologous transplant was performed in 111 patients, whereas other patients were treated with novel agents, including proteasome inhibitors and IMiDs (362 patients), or traditional chemotherapy (91 patients). The results favored the second autologous transplant, because the median survival was 4 years with the second autologous transplant, 3.3 years with the novel agents, and 2.5 years with the conventional chemotherapy drugs.

Single-molecule analysis reveals widespread structural variation in multiple myeloma.
Proc Natl Acad Sci U S A. 2015 Jun 23;112(25):7689-94.
Gupta A, Place M, Goldstein S, Sarkar D, Zhou S, Potamousis K, Kim J, Flanagan C, Li Y, Newton MA, Callander NS, Hematti P, Bresnick EH, Ma J, Asimakopoulos F, Schwartz DC.

Cyclophosphamide-based hematopoietic stem cell mobilization before autologous stem cell transplantation in newly diagnosed multiple myeloma.
J Clin Apher. 2015 Jun;30(3):176-82.
Tuchman SA, Bacon WA, Huang LW, Long G, Rizzieri D, Horwitz M, Chute JP, Sullivan K, Morris Engemann A, Yopp A, Li Z, Corbet K, Chao N, Gasparetto C.

This study questions the use of cyclophosphamide as mobilization strategy for collecting stem cells in patients with multiple myeloma, because it increased toxicity and it did not improve long-term outcomes. Patients underwent stem cell collection with either G-CSF alone (73 patients) or cyclophosphamide + G-CSF (94 patients). Results:
  - Total CD34 cells/Kg collected: 5.8 million with C-CSF vs 12 million with cyclophosphamide + G-CSF
  - Hospitalizations due to complications: 0% with G-CSF vs 14% with cyclophosphamide + G-CSF
  - Overall survival was similar in the two groups



Giampaolo Talamo, MD