APRIL 2014

Bortezomib, melphalan, prednisone (VMP) versus melphalan, prednisone, thalidomide (MPT) in elderly newly diagnosed multiple myeloma patients: A retrospective case-matched study.
Am J Hematol. 2014 Apr;89(4):355-62.
Morabito F, Bringhen S, Larocca A, Wijermans P, Victoria Mateos M, Gimsing P, Mazzone C, Gottardi D, Omedè P, Zweegman S, José Lahuerta J, Zambello R, Musto P, Magarotto V, Schaafsma M, Oriol A, Juliusson G, Cerrato C, Catalano L, Gentile M, Isabel Turel A, Marina Liberati A, Cavalli M, Rossi D, Passera R, Rosso S, Beksac M, Cavo M, Waage A, San Miguel J, Boccadoro M, Sonneveld P, Palumbo A, Offidani M.

The clinical outcomes of 296 patients treated with MPV (melphalan, prednisone, and bortezomib) were retrospectively compared with those of 294 patients treated with MPT (melphalan, prednisone, and thalidomide). Patients had newly diagnosed myeloma and were older than 65. The results were better with MPV:
  - Complete response rate: 21% with MPV and 13% with MPT
  - Median progression-free survival: 32 months with MPV and 23 months with MPT
  - Median overall survival: 80 months with MPV and 45 months with MPT

Deep sequencing reveals myeloma cells in peripheral blood in majority of multiple myeloma patients.
Clin Lymphoma Myeloma Leuk. 2014 Apr;14(2):131-139.e1.
Vij R, Mazumder A, Klinger M, O'Dea D, Paasch J, Martin T, Weng L, Park J, Fiala M, Faham M, Wolf J.
With a sequencing-based method, the authors could detect malignant plasma cells in the peripheral blood of myeloma patients with very high sensitivity, at levels <1:1,000,000 WBC. The vast majority of patients (44/46, 96%) of patients has detectable circulating plasma cells, and the levels in the peripheral blood were approximately 11 times lower than levels in the bone marrow.

Jumping translocations of 1q12 in multiple myeloma: a novel mechanism for deletion of 17p in cytogenetically defined high-risk disease.
Blood. 2014 Apr 17;123(16):2504-12. doi: 10.1182/blood-2013-12-546077. Epub 2014 Feb 4.
Sawyer JR, Tian E, Heuck CJ, Epstein J, Johann DJ, Swanson CM, Lukacs JL, Johnson M, Binz R, Boast A, Sammartino G, Usmani S, Zangari M, Waheed S, van Rhee F, Barlogie B.


MAY 2014

Prognostic value of deep sequencing method for minimal residual disease detection in multiple myeloma.
Blood. 2014 May 15;123(20):3073-9.
Martinez-Lopez J, Lahuerta JJ, Pepin F, González M, Barrio S, Ayala R, Puig N, Montalban MA, Paiva B, Weng L, Jiménez C, Sopena M, Moorhead M, Cedena T, Rapado I, Mateos MV, Rosiñol L, Oriol A, Blanchard MJ, Martínez R, Bladé J, San Miguel J, Faham M, García-Sanz R.

Serum free immunoglobulin light chain evaluation as a marker of impact from intraclonal heterogeneity on myeloma outcome.
Blood. 2014 May 29;123(22):3414-9.
Brioli A, Giles H, Pawlyn C, Campbell JP, Kaiser MF, Melchor L, Jackson GH, Gregory WM, Owen RG, Child JA, Davies FE, Cavo M, Drayson MT, Morgan GJ.
This is a prospective study that observed a "light-chain escape" in 54 of 520 patients with multiple myeloma in progression. Light chain escape occurs when a growing subclone of malignant plasma cells secretes only light chains instead of the entire immunoglobulin molecule. This phenomenon underscores the importance of monitoring light chains during the routine assessment of the response to therapy.


JUNE 2014

Patterns of central nervous system involvement in relapsed and refractory multiple myeloma.
Clin Lymphoma Myeloma Leuk. 2014 Jun;14(3):211-4.
Abdallah AO, Atrash S, Shahid Z, Jameel M, Grazziutti M, Apewokin S, Kumar NS, Restrepo A, Waheed S, Van Rhee F, Heuck CJ, Johann D Jr, Barlogie B1, Usmani SZ.
This retrospective study identified 35 cases of myeloma involving the central nervous system (CNS) in a database of 3738 patients with multiple myeloma (= 0.9%) seen at the Myeloma Institute for Research and Therapy of the University of Arkansas between 1996 and 2012. The authors believe that the CNS involvement is due to either hematogenous spread of plasma cells, or direct spread of plasma cells from the lytic lesions in the skull. Prognosis was poor, because median survival after the diagnosis of CNS involvement was only 4 months.

Comparison of 1-day vs 2-day dosing of high-dose melphalan followed by autologous hematopoietic cell transplantation in patients with multiple myeloma.
Bone Marrow Transplant. 2014 Jun;49(6):761-6.
Parmar SR, Bookout R, Shapiro JF, Tombleson R, Perkins J, Kim J, Yue B, Tomblyn M, Alsina M, Nishihori T.
The authors retrospectively compared two different conditioning regimens of high-dose melphalan: 100 mg/m2 for 2 days (185 patients) and 200 mg/m2 in 1 day (93 patients). No meaningful differences were observed, in terms of clinical outcomes, with the exception of oral mucositis, which was more pronounced in the 2-days regimen.

Polyclonal serum IgM level identifies a subgroup of multiple myeloma patients with low-risk clinicobiological features and superior survival.
Leuk Res. 2014 Jun;38(6):666-72.
An G, Wang H, Qin X, Shi L, Xu Y, Deng S, Sui W, Zhu G, Yao H, Yi S, Qin Y, Li F, Hao M, Ru K, Qi J, Cheng T, Wang J, Chang H, Qiu L.
This study of 485 myeloma patients found that the presence of normal IgM levels >50 mg/dL was associated with better biological features and better prognosis. Maybe this is due to the fact that higher IgM levels reflect a higher number of normal plasma cells/lower number of malignant plasma cells. 

Next-generation sequencing of peripheral B-lineage cells pinpoints the circulating clonotypic cell pool in multiple myeloma.
Blood. 2014 Jun 5;123(23):3618-21.
Thiele B, Kloster M, Alawi M, Indenbirken D, Trepel M, Grundhoff A, BinderM.
Until this study, some expert speculated that the clonogenic population of malignant plasma cells consisted of less differentiated pre-switch B cells. Instead, these authors demonstrated that the clonogenic cells are differentiated post-switch plasma cells (which circulate in the peripheral blood). 

Auer rod-like inclusions in plasma cells in multiple myeloma.
J Clin Pathol. 2014 Jun;67(6):547-8.
Ho WK, Zantomio D.
Auer rods are rod-shaped cytoplasmic inclusions, usually observed in patients with acute myelogenous leukemia. Interestingly, most cases of Auer rods reported in multiple myeloma were associated with production of kappa light chains. They do not contain immunoglobulins/light chains. They stain negatively for myeloperoxidase (unlike AML) and positive for alpha-naphtyl acetate esterase and beta-glucuronidase, which suggests a lysosomal origin.

Phase 2 randomized study of bortezomib-melphalan-prednisone with or without siltuximab (anti-IL-6) in multiple myeloma.
Blood. 2014 Jun 26;123(26):4136-42.
San-Miguel J, Bladé J, Shpilberg O, Grosicki S, Maloisel F, Min CK, Polo Zarzuela M, Robak T, Prasad SV, Tee Goh Y, Laubach J, Spencer A, Mateos MV, Palumbo A, Puchalski T, Reddy M, Uhlar C, Qin X, van de Velde H, Xie H, Orlowski RZ.
This is a phase II randomized study of VMP vs VMP + siltuximab in 106 patients with newly diagnosed multiple myeloma, transplant ineligible. Siltuximab was given at 11 mg/Kg every 3 weeks during induction, and for maintenance as well. All clinical outcomes, including response rates, median progression-free survival, and median overall survival, were similar in the two arms of the study, and, therefore, this was a negative trial. Of note, siltuximab was approved by the FDA for the treatment of multicentric Castleman disease in April 2014, two months before this study was published.



Giampaolo Talamo, MD