A Randomized Phase II Trial of Fludarabine/Melphalan 100 versus Fludarabine/Melphalan 140 Followed by Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Multiple Myeloma.
Biol Blood Marrow Transplant. 2013 Oct;19(10):1453-8.
Bashir Q, Khan H, Thall PF, Liu P, Shah N, Kebriaei P, Parmar S, Oran B, Ciurea S, Nieto Y, Jones R, Hosing CM, Popat UR, Dinh YT, Rondon G, Orlowski RZ, Shah JJ, De Lima M, Shpall E, Champlin R, Giralt S, Qazilbash MH.
This is a study of 50 patients with newly diagnosed or relapsed myeloma, who were randomized between two different "Flu/Cy" conditioning regimens for an allogeneic stem cell transplant: FM100 (fludarabine 120 mg/m2 + melphalan 100 mg/m2) vs FM140 (fludarabine 120 mg/m2 + melphalan 140 mg/m2). There was no significant difference in terms of toxicities and clinical outcomes. Median progression-free survival was 11.7 vs 8.4 months (p= 0.12).

Vorinostat or placebo in combination with bortezomib in patients with multiple myeloma (VANTAGE 088): a multicentre, randomised, double-blind study.
Lancet Oncol. 2013 Oct;14(11):1129-1140.
Dimopoulos M, Siegel DS, Lonial S, Qi J, Hajek R, Facon T, Rosinol L, Williams C, Blacklock H, Goldschmidt H, Hungria V, Spencer A, Palumbo A, Graef T, Eid JE, Houp J, Sun L, Vuocolo S, Anderson KC.
317 patients with relapsed (but non-refractory) myeloma were randomized to bortezomib + vorinostat vs bortezomib + placebo. The vorinostat arm had a statistically significant prolongation of median progression-free survival, but this was not significant from the clinical point of view (7.6 vs 6.8 months, p= 0.01).

Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial.
Lancet Oncol. 2013 Oct;14(11):1055-1066.
Miguel JS, Weisel K, Moreau P, Lacy M, Song K, Delforge M, Karlin L, Goldschmidt H, Banos A, Oriol A, Alegre A, Chen C, Cavo M, Garderet L, Ivanova V, Martinez-Lopez J, Belch A, Palumbo A, Schey S, Sonneveld P, Yu X, Sternas L, Jacques C, Zaki M, Dimopoulos M.
302 patients with relapsed/refractory myeloma, previously treated with both lenalidomide and bortezomib, were randomized to pomalidomide 4 mg PO qd on days 1-21 every 28 days + low-dose dexamethasone (= 40 mg PO once a week) vs high-dose dexamethasone (= 40 mg PO on days 1-4, 9-12, and 17-20). Median follow-up was 10 months. Results:
  - Response rate was 31% in the low-dose Dex arm
  - Median progression-free survival was 4 months with low-dose Dex, and 1.9 months with high-dose Dex
  - Median overall survival was 12.7 months with low-dose Dex, and 8.1 months with high-dose Dex (p= 0.03)

Comparable efficacy and lower cost of PBSC mobilization with intermediate-dose cyclophosphamide and G-CSF compared with plerixafor and G-CSF in patients with multiple myeloma treated with novel therapies.
Bone Marrow Transplant. 2013 Oct;48(10):1279-84.
Awan F, Kochuparambil ST, Falconer DE, Cumpston A, Leadmon S, Watkins K, Deremer D, Jillella A, Craig M, Hamadani M.
Mobilization chemotherapy with intermediate-dose cyclophosphamide, 3-4 g/m2 + G-CSF (55 patients) provided a higher median number of stem cells that G-CSF + plerixafor (33 patients): 16.6 vs 11.6 million CD34+ cells/Kg. Although the total cost of collection was higher in the plerixafor group, we should note that 16% of patients in the cyclophosphamide group experienced neutropenic fever.

PANORAMA 2: panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory myeloma.
Blood. 2013 Oct 3;122(14):2331-7.
Richardson PG, Schlossman RL, Alsina M, Weber DM, Coutre SE, Gasparetto C, Mukhopadhyay S, Ondovik MS, Khan M, Paley CS, Lonial S.
Among 55 patients with relapsed and bortezomib-refractory myeloma, clinical benefit rate of panobinostat + bortezomib + dexamethasone was 53% (10 minimal responses, 18 partial responses, and 1 near-CR). Median progression-free survival was 5.4 months.

Pomalidomide, cyclophosphamide, and prednisone for relapsed/refractory multiple myeloma: a multicenter phase 1/2 open-label study.
Blood. 2013 Oct 17;122(16):2799-806.
Larocca A, Montefusco V, Bringhen S, Rossi D, Crippa C, Mina R, Galli M, Marcatti M, La Verde G, Giuliani N, Magarotto V, Guglielmelli T, Rota-Scalabrini D, Omedé P, Santagostino A, Baldi I, Carella AM, Boccadoro M, Corradini P, Palumbo A.
In this study, 69 patients with relapsed/refractory myeloma received chemotherapy with PCP:
  - Pomalidomide 1-2.5 mg PO daily (maximum tolerated dose was 2.5 mg)
  - Cyclophosphamide 50 mg PO every other day
  - Prednisone 50 mg PO every other day
This chemotherapy was given for 6 cycles of 28 days, followed by maintenance therapy with pomalidomide 1 mg daily and prednisone 25 mg every other day.
Median follow-up was 15 months. Results:
  - PR: 51%
  - Median progression-free survival: 10.4 months (median EFS was 5 months in historical controls)
  - Median overall survival: not reached (median OS was 9 months in historical controls)
  - 1-year survival: 69%

Phase 2 dose-expansion study (PX-171-006) of carfilzomib, lenalidomide, and low-dose dexamethasone in relapsed or progressive multiple myeloma.
Blood. 2013 Oct 31;122(18):3122-8.
Wang M, Martin T, Bensinger W, Alsina M, Siegel DS, Kavalerchik E, Huang M, Orlowski RZ, Niesvizky R.
In this study, 52 patients with relapsed/refractory myeloma were treated with CRD (carfilzomib, lenalidomide, and dexamethasone). Response rate: 77%. Median time to response was 1 month (range, 0.5-4.6). Median progression-free survival: 15 months.

Multiple pesticide exposures and the risk of multiple myeloma in Canadian men.
Int J Cancer. 2013 Oct 15;133(8):1846-58.
Kachuri L, Demers PA, Blair A, Spinelli JJ, Pahwa M, McLaughlin JR, Pahwa P, Dosman JA, Harris SA.
This is a case-control study with 342 cases of multiple myeloma and 1,357 controls. It reported significant associations for some pesticides, suggesting that some chemicals (carbamate pesticides, phenoxy herbicides, organochlorines, carbaryl, captan, and mecoprop) may be risk factors for multiple myeloma.



Long-term Follow-up of MRC Myeloma IX Trial: Survival Outcomes with Bisphosphonate and Thalidomide Treatment.
Clin Cancer Res. 2013 Nov 1;19(21):6030-8.
Morgan GJ, Davies FE, Gregory WM, Bell SE, Szubert AJ, Cook G, Drayson MT, Owen RG, Ross FM, Jackson GH, Child JA.
The administration of zoledronic acid improved median overall survival in a study of 1,970 myeloma patients (compared to clodronic acid). Interestingly, maintenance therapy with thalidomide was associated with a shorter overall survival in patients with high-risk cytogenetics. In the overall group, it improved PFS but not OS.

Reduced intensity-conditioned allogeneic stem cell transplantation for multiple myeloma relapsing or progressing after autologous transplantation: a study by the European Group for Blood and Marrow Transplantation.
Bone Marrow Transplant. 2013 Nov;48(11):1395-400.
Auner HW, Szydlo R, van Biezen A, Iacobelli S, Gahrton G, Milpied N, Volin L, Janssen J, Nguyen Quoc S, Michallet M, Schoemans H, El Cheikh J, Petersen E, Guilhot F, Schönland S, Ahlberg L, Morris C, Garderet L, de Witte T, Kröger N.
Reduced-intensity conditioned allogeneic stem cell transplant was performed in 413 patients with myeloma. All patient had disease relapse after 1 or more autologous transplants. Results:
  - Non-relapse mortality at 1 year: 21%.
  - Median progression-free survival: 10 months. PFS was better with CMV seronegativity of both patient and donor, and with patient-donor gender mismatch.
  - Median overall survival: 25 months.

Consolidation with VTd significantly improves the complete remission rate and time to progression following VTd induction and single autologous stem cell transplantation in multiple myeloma.
Leukemia. 2013 Nov;27(11):2242-4.
Leleu X, Fouquet G, Hebraud B, Roussel M, Caillot D, Chrétien ML, Arnulf B, Szalat R, Garderet L, Benajiba L, Pegourie B, Regny C, Royer B, Caulier A, Stoppa AM, Garciaz S, Touzeau C, Chaleteix C, Fermand JP, Loiseau HA, Facon T, Attal M, Moreau P.
This retrospective study compares outcomes of 96 myeloma patients treated with VTD (bortezomib, thalidomide, and dexamethasone) x 3 cycles + autologous stem cell transplant, with those of 121 patients treated with VTD + autologous stem cell transplant, followed by a consolidation with 2 additional cycles of VTD. None of the patients received maintenance therapy. Median follow-up was 30 months. Results favored the consolidation group:
  - CR: 30% post-transplant, and 52% post-consolidation
  - Median time to progression: 25 months with VTD-SCT and "not reached" with VTD-SCT-VTD
  - Estimated 4-year progression-free survival: 29% with VTD-SCT and 62% with VTD-SCT-VTD

Myeloma cell morphology and morphometry in correlation with clinical stages and survival.
Diagn Cytopathol. 2013 Nov;41(11):947-54.
Seili-Bekafigo I, Valković T, Babarović E, Duletić-Načinović A, Jonjić N.



Vertebral augmentation in the treatment of pathologic compression fractures in 792 patients with multiple myeloma.
Leukemia. 2013 Dec;27(12):2391-3.
Erdem E, Samant R, Malak SF, Culp WC, Brown A, Peterson L, Lensing S, Barlogie B.
This is a retrospective review of 2693 vertebral augmentation procedures in 792 patients with multiple myeloma and spinal compression fractures. Vertebroplasty was the procedure used in 83% of cases. Results:
  - Distribution: T1-T10 37%, T11-L2 39%, L3-sacrum 24%
  - Pain levels reduced, from a pre-procedure average score of 6.9, to a post-procedure average score of 4.2 (using a 0-10 pain level scale).
  - Use of narcotic analgesics reduced from a baseline of 70% to 48% after the procedure.

Importance of achieving stringent complete response after autologous stem-cell transplantation in multiple myeloma.
J Clin Oncol. 2013 Dec 20;31(36):4529-35.
Kapoor P, Kumar SK, Dispenzieri A, Lacy MQ, Buadi F, Dingli D, Russell SJ, Hayman SR, Witzig TE, Lust JA, Leung N, Lin Y, Zeldenrust SR, McCurdy A, Greipp PR, Kyle RA, Rajkumar SV, Gertz MA.
This is a study of 445 consecutive patients who underwent an autologous stem cell transplantation for multiple myeloma. The depth of response after transplant influenced their survival. The 5-year survival rate was 47% in patients with near-CR, 53% in patients in CR, and 80% in patients with sCR (= stringent CR, 25% of cases).



Giampaolo Talamo, MD