APRIL 2013

Second auto-SCT for treatment of relapsed multiple myeloma.
Bone Marrow Transplant. 2013 Apr;48(4):568-73.
Gonsalves WI, Gertz MA, Lacy MQ, Dispenzieri A, Hayman SR, Buadi FK, Dingli D, Hogan WJ, Kumar SK.
98 patients with relapsed myeloma underwent a second autologous transplant as salvage strategy. Transplant-related mortaity was 4%. Median progression-free survival after the second stem cell transplant was 10 months. Shorter PFS was predicted by:
  - Higher number of previous treatment regimens
  - Failure to achieve complete remission after the second transplant
  - Shorter remission after the first transplant

Body Mass Index and Physical Activity at Different Ages and Risk of Multiple Myeloma in the NIH-AARP Diet and Health Study.
Am J Epidemiol. 2013 Apr 15;177(8):776-86.
Hofmann JN, Moore SC, Lim U, Park Y, Baris D, Hollenbeck AR, Matthews CE, Gibson TM, Hartge P, Purdue MP.
This epidemiological study supports the hypothesis that obesity is a risk factor for multiple myeloma.

Efficacy of thalidomide-based therapy following lenalidomide plus dexamethasone in patients with relapsed/refractory multiple myeloma.
Am J Hematol. 2013 Apr;88(4):337-8.
Kukreti V, Masih-Khan E, Young T, Chu CM, Jiang H, Trudel S, Chen C, Jimenez-Zepeda V, Reece DE.
This retrospective study of 24 patients with myeloma refractory to lenalidomide (or intolerant to lenalidomide) received salvage treatment with thalidomide. Response rate was 38% (all VGPR or PR, no CR), and median progression-free survival was only 3 months.

Phase Ib Dose-Escalation Study (PX-171-006) of Carfilzomib, Lenalidomide, and Low-Dose Dexamethasone in Relapsed or Progressive Multiple Myeloma.
Clin Cancer Res. 2013 Apr 15;19(8):2248-56.
Niesvizky R, Martin TG 3rd, Bensinger WI, Alsina M, Siegel DS, Kunkel LA, Wong AF, Lee S, Orlowski RZ, Wang M.
This phase I study identified the maximum dose for CRD:
  - Carfilzomib 27 mg/m2 IV on days 1,2, 8,9, 15,16
  - Revlimid 25 mg PO on days 1-21
  - Dexamethasone 40 mg PO weekly
Cycles were repeated every 28 days. Response rate was 62.5%, and median progression-free survival was 10 months.

The CCND1 c.870G>A polymorphism is a risk factor for t(11;14)(q13;q32) multiple myeloma.
Nat Genet. 2013 Apr 26;45(5):522-5.
Weinhold N, Johnson DC, Chubb D, Chen B, Försti A, Hosking FJ, Broderick P, Ma YP, Dobbins SE, Hose D, Walker BA, Davies FE, Kaiser MF, Li NL, Gregory WA, Jackson GH, Witzens-Harig M, Neben K, Hoffmann P, Nöthen MM, Mühleisen TW, Eisele L, Ross FM, Jauch A, Goldschmidt H, Houlston RS, Morgan GJ, Hemminki K.
This study indicates that genetic factors confer a risk of a specific chromosomal translocation.

Characterization of IGH locus breakpoints in multiple myeloma indicates a subset of translocations appear to occur in pregerminal center B cells.
Blood. 2013 Apr 25;121(17):3413-9.
Walker BA, Wardell CP, Johnson DC, Kaiser MF, Begum DB, Dahir NB, Ross FM, Davies FE, Gonzalez D, Morgan GJ.
In this study of translocation analysis in 61 myeloma samples, the authors found that 100% of the t(4;14) translocations were mediated by class switch recombination in mature B cells in the germinal center. Unexpectedly, 21% of the t(11;14) and 25% of the t(14;20) were generated during the DH-JH recombination in pro-B-cells in the bone marrow.

Serum free light chain ratio as a biomarker for high-risk smoldering multiple myeloma.
Leukemia. 2013 Apr;27(4):941-6.
Larsen JT, Kumar SK, Dispenzieri A, Kyle RA, Katzmann JA, Rajkumar SV.
After a retrospective review of 5865 patients with smoldering myeloma seen at the Mayo Clinic between 1970 and 2010, the authors found that a serum involved/uninvolved FLC ratio >100 (seen in 15% of cases) had a 98% chance to progress to symptomatic myeloma within a median follow-up of 52 months (vs 56% in all patients), and a 72% risk of progressing to symptomatic myeloma within 2 years.

Intravenous injection of bortezomib, melphalan and dexamethasone in refractory and relapsed multiple myeloma.
Ann Oncol. 2013 Apr;24(4):1038-44.
Romano A, Chiarenza A, Consoli U, Conticello C, Forte S, Uccello G, Vetro C, Cavalli M, Coppolino F, Palumbo GA, Di Raimondo F.
50 patients with previously treated myeloma received Mel-Dex-Vel. Most patients received all 3 drugs once a week:
  - Melphalan 5 mg/m2 IV
  - Dexamethasone 40 mg IV
  - Bortezomib 1.3 mg/m2 IV
Response rate was 62%, and median progression-free survival was 22 months. Toxicity was acceptable.


MAY 2013

A phase 2 multicentre study of siltuximab, an anti-interleukin-6 monoclonal antibody, in patients with relapsed or refractory multiple myeloma.
Br J Haematol. 2013 May;161(3):357-66.
Voorhees PM, Manges RF, Sonneveld P, Jagannath S, Somlo G, Krishnan A, Lentzsch S, Frank RC, Zweegman S, Wijermans PW, Orlowski RZ, Kranenburg B, Hall B,
Casneuf T, Qin X, van de Velde H, Xie H, Thomas SK.
Fifty-three patients with relapsed/refractory myeloma were treated with siltuximab +/- dexamethasone. Single-agent siltuximab was ineffective (no responses), and combination therapy with siltuximab + dexamethasone had a modest effect: RR was 17% (partial responses), and median progression-free survival was 3.7 months.

Bisphosphonate-associated osteonecrosis of the external auditory canal.
J Laryngol Otol. 2013 May 15:1-3.
Wickham N, Crawford A, Carney AS, Goss AN.

Salvage second hematopoietic cell transplantation in myeloma.
Biol Blood Marrow Transplant. 2013 May;19(5):760-6.
Michaelis LC, Saad A, Zhong X, Le-Rademacher J, Freytes CO, Marks DI, Lazarus HM, Bird JM, Holmberg L, Kamble RT, Kumar S, Lill M, Meehan KR, Saber W, Schriber J, Tay J, Vogl DT, Wirk B, Savani BN, Gale RP, Vesole DH, Schiller GJ, Abidi M, Anderson KC, Nishihori T, Kalaycio ME, Vose JM, Moreb JS, Drobyski W, Munker R, Roy V, Ghobadi A, Holland HK, Nath R, To LB, Maiolino A, Kassim AA, Giralt SA, Landau H, Schouten HC, Maziarz RT, Michael J, Kindwall-Keller T, Stiff PJ, Gibson J, Lonial S, Krishnan A, Dispenzieri A, Hari P; Plasma Cell Disorders Working Committee of the Center for International Blood and Marrow Transplant Research.
This study reports the outcomes of 187 patients who underwent a second autologous stem cell transplant for relapsed/refractory myeloma. Patients previously treated with tandem transplants were excluded from the analysis. Median interval between the first SCT and relapse/progression of myeloma was 18 months, and median interval between the first transplant and the second one was 32 months. At 3 years, progression-free survival was 13%, and overall survival was 46%. As expected, the benefit of the second SCT done as salvage therapy was greater in those patients who experienced a longer (>36 months) period of disease remission after the first SCT.


JUNE 2013

Improved accuracy of discrimination between IgM Multiple Myeloma and Waldenström Macroglobulinaemia by testing for MYD88 L265P mutations.
Br J Haematol. 2013 Jun;161(6):902-4.
Willenbacher W, Willenbacher E, Brunner A, Manzl C.
The authors report the presence of typical MYD88 L265P exon 5 mutations in 6 of 7 patients with Waldenstrom macroglobulinemia, and in 0 of 4 patients with IgM myeloma. They conclude that the MYD88 mutational status may be useful for discriminating between WM and IgM-MM.

Complete remission achieved with single agent CNTO 328, an anti-IL-6 monoclonal antibody, in relapsed and refractory myeloma.
Clin Lymphoma Myeloma Leuk. 2013 Jun;13(3):333-7.
Chari A, Pri-Chen H, Jagannath S.

Plasma cell neoplasms in US solid organ transplant recipients.
Am J Transplant. 2013 Jun;13(6):1523-32.
Engels EA, Clarke CA, Pfeiffer RM, Lynch CF, Weisenburger DD, Gibson TM, Landgren O, Morton LM.

Among 202,600 solid organ transplant recipients, 140 patients developed plasma cell neoplasms (102 cases of myeloma and 38 cases of plasmacytomas). Although the risk was 1.8-fold increased relative to the general population (95% CI 1.5-2.1), I am not particularly impressed by the frequency: only 1 case of myeloma in 1986 transplanted patients.

High expression of cereblon (CRBN) is associated with improved clinical response in patients with multiple myeloma treated with lenalidomide and dexamethasone.
Br J Haematol. 2013 Jun;161(5):695-700.
Heintel D, Rocci A, Ludwig H, Bolomsky A, Caltagirone S, Schreder M, Pfeifer S, Gisslinger H, Zojer N, Jäger U, Palumbo A.

Allogeneic hematopoietic cell transplantation from unrelated donors in multiple myeloma: study from the Italian Bone Marrow Donor Registry.
Biol Blood Marrow Transplant. 2013 Jun;19(6):940-8.
Passera R, Pollichieni S, Brunello L, Patriarca F, Bonifazi F, Montefusco V, Falda M, Montanari M, Guidi S, Giaccone L, Mordini N, Carella AM, Bavaro P, Milone G, Benedetti F, Ciceri F, Scimè R, Benedetti E, Castagna L, Festuccia M, Rambaldi A, Bacigalupo A, Corradini P, Bosi A, Boccadoro M, Bandini G, Fanin R, Bruno B.
This is a study of 196 consecutive myeloma patients treated with a stem cell transplant from unrelated donors, between 2000 and 2009. The long-term results were disappointing, because the median event-free survival was:
  - 10 months with myeloablative regimens (OS 29 months)
  -   6 months with reduced-intensity regimens (OS 11 months)
  - 13 months with nonmyeloablative regimens (OS 32 months)

D(T)PACE as salvage therapy for aggressive or refractory multiple myeloma.
Br J Haematol. 2013 Jun;161(6):802-10.
Gerrie AS, Mikhael JR, Cheng L, Jiang H, Kukreti V, Panzarella T, Reece D, Stewart KA, Trieu Y, Trudel S, Chen CI.
This is a retrospective study of 75 patients with relapsed/refractory myeloma treated with D(T)-PACE chemotherapy. Overall response rate was 49% (PR 33%, VGPR 16%). The duration of remission was short, because median progression-free survival was 5.5 months. Median OS was 14 months.

Bortezomib consolidation after autologous stem cell transplantation in multiple myeloma: a Nordic Myeloma Study Group randomized phase 3 trial.
Blood. 2013 Jun 6;121(23):4647-54.
Mellqvist UH, Gimsing P, Hjertner O, Lenhoff S, Laane E, Remes K, Steingrimsdottir H, Abildgaard N, Ahlberg L, Blimark C, Dahl IM, Forsberg K, Gedde-Dahl T, Gregersen H, Gruber A, Guldbrandsen N, Haukås E, Carlson K, Kvam AK, Nahi H, Lindås R, Andersen NF, Turesson I, Waage A, Westin J; Nordic Myeloma Study Group.
This is a study of 370 myeloma patients treated with an autologous stem cell transplant and randomized to consolidation with 21 weeks of bortezomib vs no consolidation. Bortezomib improved progression-free survival (27 vs 20 months) but not overall survival. Consolidation with bortezomib did not seem to be beneficial for those patients who reached at least a VGPR after the transplant. 

Autologous/reduced-intensity allogeneic stem cell transplantation vs autologous transplantation in multiple myeloma: long-term results of the EBMT-NMAM2000 study.
Blood. 2013 Jun 20;121(25):5055-63.
Gahrton G, Iacobelli S, Björkstrand B, Hegenbart U, Gruber A, Greinix H, Volin L, Narni F, Carella AM, Beksac M, Bosi A, Milone G, Corradini P, Schönland S, Friberg K, van Biezen A, Goldschmidt H, de Witte T, Morris C, Niederwieser D, Garderet L, Kröger N; EBMT Chronic Malignancies Working Party Plasma Cell Disorders Subcommittee.



Giampaolo Talamo, MD