OCTOBER 2015

Phase 2 study of dovitinib in patients with relapsed or refractory multiple myeloma with or without t(4;14) translocation.
Eur J Haematol. 2015 Oct;95(4):316-24.
Scheid C, Reece D, Beksac M, Spencer A, Callander N, Sonneveld P, Kalimi G, Cai C, Shi M, Scott JW, Stewart AK.
In this study, 43 patients with relapsed or refractory myeloma were treated with dovitinib, a receptor tyrosine kinase inhibitor that targets FGFR3. Thirteen patients had the t(4;14) translocation. The results were disappointing, because no objective responses were observed.

Radiologic and clinical characteristics of vertebral fractures in multiple myeloma.
Spine J. 2015 Oct 1;15(10):2149-56.
Miller JA, Bowen A, Morisada MV, Margetis K, Lubelski D, Lieberman IH, Benzel EC, Mroz TE.

This is a retrospective study of 124 vertebral fractures in 50 patients with multiple myeloma. The most commonly involved site is the thoracic spine. Types of vertebral fractures are: biconcave (55%), wedge (32%), and crush (13).

Risks, severity and timing of infections in patients with multiple myeloma: a longitudinal cohort study in the era of immunomodulatory drug therapy.
Br J Haematol. 2015 Oct;171(1):100-8.
Teh BW, Harrison SJ, Worth LJ, Spelman T, Thursky KA, Slavin MA.

A comparison of salvage infusional chemotherapy regimens for recurrent/refractory multiple myeloma.
Cancer. 2015 Oct 15;121(20):3622-30.
Griffin PT, Ho VQ, Fulp W, Nishihori T, Shain KH, Alsina M, Baz RC.

This is a retrospective study comparing the outcomes of 3 different regimens of conventional IV agents:
  - CVAD = cyclophosphamide, vincristine, doxorubicin, dexamethasone (33 patients)
  - DCEP = dexamethasone, cyclophosphamide, etoposide, cisplatin (52 patients)
  - VDT-PACE = bortezomib, dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, etoposide (22 patients)
 All clinical outcomes were similar, with response rate 55%, median progression-free survival 4.5 months, and median overall survival 8.5 months. DCEP was probably the least toxic regimen.

Incidence of infection according to intravenous immunoglobulin use in autologous hematopoietic stem cell transplant recipients with multiple myeloma.
Transpl Infect Dis. 2015 Oct;17(5):679-87.
Park S, Jung CW, Jang JH, Kim SJ, Kim WS, Kim K.
This is a retrospective study of 162 patients with myeloma who underwent an autologous stem cell transplant. The prophylactic use of IVIG did not seem to reduce the incidence of infections (35% without IVIG, and 31% with IVIG, p=0.63), and the incidence of infections requiring hospitalization.

Continuous Therapy Versus Fixed Duration of Therapy in Patients With Newly Diagnosed Multiple Myeloma.
J Clin Oncol. 2015 Oct 20;33(30):3459-66.
Palumbo A, Gay F, Cavallo F, Di Raimondo F, Larocca A, Hardan I, Nagler A, Petrucci MT, Hajek R, Pezzatti S, Delforge M, Patriarca F, Donato F, Cerrato C, Nozzoli C, Yu Z, Boccadifuoco L, Caravita T, Benevolo G, Guglielmelli T, Vincelli D, Jacques C, Dimopoulos MA, Ciccone G, Musto P, Corradini P, Cavo M, Boccadoro M.
In many clinical trials, a valuable end point is the progression-free survival (PFS), which is the time from therapy assignment until the first progression or death. These authors explore a new end point, the PFS2, defined as the time from therapy assignment until the second progression of death), with the goal of clarifying whether a continuous first-line therapy would be associated to a shorter second remission, as opposed to a fixed first-line therapy. In fact, some experts expressed the concern that a continuous first-line therapy would lead to drug-resistant myeloma cells, and that the disease could become more aggressive and less responsive to the second-line therapy. In other words, the remission with the second-line chemotherapy would be shorter if the first-line chemotherapy would be continued until progression. However, this study showed that continuous therapy is superior to fixed duration therapy. The authors analyzed data from three trials, including 417 patients who received continuous therapy, and 410 patients who received fixed duration therapy. In this analysis, patients in remission after first-line therapy, as well as patients who progressed after first-line therapy but are in remission after second-line therapy, are censored. Results:
  - Median PFS1: 32 months with continuous therapy, and 16 months with fixed duration therapy
  - Median PFS2: 55 months with continuous therapy, and 40 months with fixed duration therapy
 - Overall survival at 4 years: 69% months with continuous therapy, and 60% with fixed duration therapy
These results suggest that continuing chemotherapy indefinitely, until tumor progression, does not induce significant resistance to an additional line of chemotherapy.

Comparison of (18)F-FDG PET/CT and PET/MRI in patients with multiple myeloma.
Am J Nucl Med Mol Imaging. 2015 Oct 12;5(5):469-78.
Sachpekidis C, Hillengass J, Goldschmidt H, Mosebach J, Pan L, Schlemmer HP, Haberkorn U, Dimitrakopoulou-Strauss A.

 

NOVEMBER 2015

Chronic neutrophilic leukaemia and plasma cell-related neutrophilic leukaemoid reactions.
Br J Haematol. 2015 Nov;171(3):400-10.
Bain BJ, Ahmad S.

Rare cases of multiple myeloma and MGUS are associated with a neutrophilic leukemoid reaction. This is due to the synthesis of G-CSF by the clonal plasma cells. Plasma G-CSF is increased.
This study tries to identify findings that distinguish chronic neutrophilic leukemia (CNL) from the leukemoid reaction associated with plasma cell disorders, and it concludes that the most important diagnostic finding of CNL is the clonality of the myeloid cells, and the presence of molecular genetic abnormalities such as mutations in CSF3R, the gene encoding the G-CSF receptor. Features such as toxic granulation, Dohle bodies, and the neutrophil alkaline phosphatase (NAP) score do not aid in the differential diagnosis.

Community-Based Phase IIIB Trial of Three UPFRONT Bortezomib-Based Myeloma Regimens.
J Clin Oncol. 2015 Nov 20;33(33):3921-9.
Niesvizky R, Flinn IW, Rifkin R, Gabrail N, Charu V, Clowney B, Essell J, Gaffar Y, Warr T, Neuwirth R, Zhu Y, Elliott J, Esseltine DL, Niculescu L, Reeves J.
This trail randomized 502 transplant-ineligible patients with multiple myeloma into three bortezomib-based treatments: VD (bortezomib-dexamethasone, 168 patients), VTD (bortezomib-thalidomide-dexamethasone, 167 patients), and VMP (bortezomib-melphalan-dexamethasone, 167 patients). After 24 weeks, patients received maintenance with weekly bortezomib for 25 weeks. The three-drug combinations VTD and VMP did not offer significantly better results compared to the two drug combination. With VD, response rate was 73%, median progression-free survival was 15 months, and median overall survival was 50 months.

Monoclonal Gammopathy in HIV-1-Infected Patients: Factors Associated With Disappearance Under Long-Term Antiretroviral Therapy.
J Acquir Immune Defic Syndr. 2015 Nov 1;70(3):250-5.
Casanova ML, Makinson A, Eymard-Duvernay S, Ouedraogo DE, Badiou S, Reynes J, Tuaillon E.

In this study, 77 patients with HIV and MGUS were followed over time. After a median follow-up of 6.8 years, the MGUS disappeared in 66% of patients, and the disappearance was associated with HIV virologic control with antiretroviral therapy, and with the absence of chronic HCV infection. Only 1 patient developed multiple myeloma, 3 years after the diagnosis of MGUS.

Carfilzomib, pomalidomide, and dexamethasone for relapsed or refractory myeloma.
Blood. 2015 Nov 12;126(20):2284-90.
Shah JJ, Stadtmauer EA, Abonour R, Cohen AD, Bensinger WI, Gasparetto C, Kaufman JL, Lentzsch S, Vogl DT, Gomes CL, Pascucci N, Smith DD, Orlowski RZ, Durie BG.
In this phase I trial, 32 patients with relapsed or refractory myeloma, all resistant to prior lenalidomide, received CPD, a combination regimen of:
  - Carfilzomib 20/27 mg/m2 IV on days 1,2, 8,9, 15,16
  - Pomalidomide 4 mg PO on days 1-21
  - Dexamethasone 40 mg PO/IV on days 1, 8, 15, 22
Cycles were repeated every 28 days. The regimen was highly active and well tolerated (1 patient died of pneumonia, and another patient dies of pulmonary embolism, but these two events could have occurred even without the chemotherapy), and the the above doses represented the MTD of the CPD regimen.

Clinical outcomes of venous thromboembolism with dalteparin therapy in multiple myeloma patients.
Thromb Res. 2015 Nov;136(5):974-9.
Lee SE, Jeon YW, Yoon JH, Cho BS, Eom KS, Kim YJ, Kim HJ, Lee S, Cho SG, Kim DW, Lee JW, Min WS, Kim M, Min CK.
In this study, 44 patients with multiple myeloma who developed venous thromboembolism were treated with dalteparin. Median duration of therapy was 4.2 months. Median follow-up was 9 months. The treatment seemed to be efficacious, because only 5 patients (11%) developed recurrent venous thromboembolism. Major bleeding was observed in 3 patients.

 

DECEMBER 2015

Contribution of chemotherapy mobilization to disease control in multiple myeloma treated with autologous hematopoietic cell transplantation.
Bone Marrow Transplant. 2015 Dec;50(12):1513-8. doi: 10.1038/bmt.2015.190. Epub 2015 Aug 24.
Uy GL, Costa LJ, Hari PN, Zhang MJ, Huang JX, Anderson KC, Bredeson CN, Callander NS, Cornell RF, Perez MA, Dispenzieri A, Freytes CO, Gale RP, Garfall A, Gertz MA, Gibson J, Hamadani M, Lazarus HM, Kalaycio ME, Kamble RT, Kharfan-Dabaja MA, Krishnan AY, Kumar SK, Kyle RA, Landau HJ, Lee CH, Maiolino A, Marks DI, Mark TM, Munker R, Nishihori T, Olsson RF, Ramanathan M, Rodriguez TE, Saad AA, Savani BN, Schiller GJ, Schouten HC, Schriber JR, Scott E, Seo S, Sharma M, Ganguly S, Stadtmauer EA, Tay J, To LB, Vesole DH, Vogl DT, Wagner JL, Wirk B, Wood WA, D'Souza A.
This is a retrospective study of 968 patients with myeloma who underwent an autologous stem cell collection. The stem cells were collected either with growth factors alone (i.e., G-CSF or GM-CSF) (519 pts), or with mobilization chemotherapy (cyclophosphamide in 338 pts, etoposide in 55 pts, cyclophosphamide + etoposide in 21 patients, or VDT-PACE/similar in 35 patients) (449 pts). The authors found there there was no significant difference of clinical outcomes between the two groups. Results:
  - Progression-free survival at 3 years: 43% with growth factors alone, and 40% with chemotherapy (p=0.33)
  - Overall survival at 5 years: 62% with growth factros alone, and 60% with chemotherapy (p=0.76)
The conclusion is that mobilization chemotherapy does not contribute to disease control in multiple myeloma.

 

 


Giampaolo Talamo, MD