A phase 2 study of single-agent carfilzomib (PX-171-003-A1) in patients with relapsed and refractory multiple myeloma.
Blood. 2012 Oct 4;120(14):2817-25.
Siegel DS, Martin T, Wang M, Vij R, Jakubowiak AJ, Lonial S, Trudel S, Kukreti V, Bahlis N, Alsina M, Chanan-Khan A, Buadi F, Reu FJ, Somlo G, Zonder J, Song K, Stewart AK, Stadtmauer E, Kunkel L, Wear S, Wong AF, Orlowski RZ, Jagannath S.
Carfilzomib was administered to 266 patients with relapsed and refractory myeloma. Patient received a median of 5 prior lines of therapy, including bortezomib (99%), corticosteroids (98%), lenalidomide (94%), thalidomide (75%), and stem cell transplant (74%). Results:
  - Response rate: 24%
  - In responders, median duration of response was 8 months
  - Median progression-free survival: 3.7 months
  - Median overall survival: 15.6 months
  - Most common adverse events: fatigue (49%), anemia (46%), nausea (45%), and thrombocytopenia (39%). Peripheral neuropathy was seen in 12% of patients.

An Open-Label Single-Arm Pilot Phase II Study (PX-171-003-A0) of Low-Dose, Single-Agent Carfilzomib in Patients With Relapsed and Refractory Multiple Myeloma.
Clin Lymphoma Myeloma Leuk. 2012 Oct;12(5):310-8.
Jagannath S, Vij R, Stewart AK, Trudel S, Jakubowiak AJ, Reiman T, Somlo G, Bahlis N, Lonial S, Kunkel LA, Wong A, Orlowski RZ, Siegel DS.
46 myeloma patients who relapsed after at least 2 therapies received bortezomib 20 mg/m2. Previous therapies included bortezomib (100%), lenalidomide (91%), and thalidomide (91%). All patients were refractory to their last therapy, i.e., they progressed within 60 days of completion of the last therapy. Median time from diagnosis was 5.5 years. Response rate was 17%, and median PFS was 3.5 months. Among responders, median duration of response was 7 months.

A phase 1 study of lucatumumab, a fully human anti-CD40 antagonist monoclonal antibody administered intravenously to patients with relapsed or refractory multiple myeloma.
Br J Haematol. 2012 Oct;159(1):58-66.
Bensinger W, Maziarz RT, Jagannath S, Spencer A, Durrant S, Becker PS, Ewald B, Bilic S, Rediske J, Baeck J, Stadtmauer EA.
With the limits of data from a phase 1 study (the goal is to find the proper dose, not to assess effectiveness), the clinical activity of single-agent lucatumumab was overall modest. Among 28 patients, there was only 1 patient with partial response, and 12 patients (43%) with stable disease.

Low-dose acyclovir prophylaxis for bortezomib-induced herpes zoster in multiple myeloma patients.
Br J Haematol. 2012 Oct;159(1):111-3.
Minarik J, Pika T, Bacovsky J, Langova K, Scudla V.
This is a retropsective analysis of 169 patients with myeloma treated with bortezomib. The development of herpes zoster was observed in:
  - 21 cases (27%) among 78 patients who did not receive acyclovir prophylaxis
  - 0% among 92 patients who received 200 mg daily (there was 1 case, but that patient was noncompliant with the medication)

Allo-SCT for multiple myeloma: a review of outcomes at a single transplant center.
Bone Marrow Transplant. 2012 Oct;47(10):1312-7.
Bensinger W, Rotta M, Storer B, Chauncey T, Holmberg L, Becker P, Sandmaier BM, Storb R, Maloney D.
This is a retrospective study of myeloma patients who underwent allogeneic stem cell transplant at the prestigious Fred Hutchinson Cancer Cancer Research Center in Seattle, WA. They included 278 patients transplanted in a period of 34 years (1975-2008): 144 myeloablative allo-SCT, done between 1975 and 2000, and 134 non-myeloablative allo-SCT, done between 1998 and 2008. Results:
  - With myeloablative all-SCT: at 15 years, overall survival was 11%, and progression-free survival 8%
  - With non-myeloablative all-SCT: at 10 years, overall survival was 39%, and progression-free survival 16%
  - The best outcomes were observed with tandem auto-allo SCT (88 patients): at 10 years, OS was 49%, and PFS 27%



Prognostic factors associated with progression of smoldering multiple myeloma to symptomatic form.
Cancer. 2012 Nov 15;118(22):5544-5549.
Rago A, Grammatico S, Za T, Levi A, Mecarocci S, Siniscalchi A, De Rosa L, Felici S, Bongarzoni V, Piccioni AL, La Verde G, Pisani F, Franceschini L, Paviglianiti AL, Caravita T, Petrucci MT, De Stefano V, Cimino G; on behalf of the Multiple Myeloma GIMEMA-Latium Region Working Group.
This is a study of 397 patients with smoldering myeloma. Progression to symptomatic myeloma occurred in 45% of cases at 10 years, and 75% of cases at 20 years. In 10 patients (2.5%) having >60% plasma cells in the bone marrow, risk of progression to symptomatic myeloma was higher, and the authors recommended starting therapy in those patients soon after diagnosis.

A phase 1 trial of the anti-KIR antibody IPH2101 in patients with relapsed/refractory multiple myeloma.
Blood. 2012 Nov 22;120(22):4324-33.
Benson DM Jr, Hofmeister CC, Padmanabhan S, Suvannasankha A, Jagannath S, Abonour R, Bakan C, Andre P, Efebera Y, Tiollier J, Caligiuri MA, Farag SS.
Myeloma cells express HLA class I molecules that acts as KIR ligands to NK cells with inhibitory KIRs. In this phase I trial, 32 patients with relapsed/refractory myeloma received IPH2101, an anti-KIR antibody. Although IPH2101 enhanced NK cell cytotoxicity against myeloma in vitro, no objective responses were seen.



Contrast enhanced MRI and (18)F-FDG PET-CT in the assessment of multiple myeloma: A comparison of results in different phases of the disease.
Eur J Radiol. 2012 Dec;81(12):4013-8.
Spinnato P, Bazzocchi A, Brioli A, Nanni C, Zamagni E, Albisinni U, Cavo M, Fanti S, Battista G, Salizzoni E.
This study retrospectively compared accuracy of MRI (210) and PET-CT scans (210) in the staging and follow-up of 191 patients with multiple myeloma. MRI performed better than PET-CT in staging and in patients with recurrent disease. PET-CT was superior in showing response to therapy, because normalization of findings was faster for PET-CT than MRI.

Bortezomib-cyclophosphamide-dexamethasone for relapsing multiple myeloma.
Am J Clin Oncol. 2012 Dec;35(6):562-5.
Fu W, Delasalle K, Wang J, Song S, Hou J, Alexanian R, Wang M.
44 patients with relapsed myeloma received CyBorD, with:
  - Cyclophosphamide 70 mg/m2 twice a day on days 1-4
  - Bortezomib 1.3 mg/m2 IV on days 1, 4, 8, 11
  - Dexamethasone 20 mg/m2 PO daily for 4 days beginning on days 1-4, 9-12, and 17-20
  - Response rate: 73% (PR 59%, CR 14%)
  - Median remission time of responding patients: 10 months
  - Median survival: 33 months in responsive disease, and 12 months with unresponsive disease.



Giampaolo Talamo, MD