Vemurafenib response in 2 patients with posttransplant refractory BRAF V600E-mutated multiple myeloma.
Clin Lymphoma Myeloma Leuk. 2014 Oct;14(5):e161-3.
Sharman JP, Chmielecki J, Morosini D, Palmer GA, Ross JS, Stephens PJ, Stafl J, Miller VA, Ali SM.

Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: a multicentre, randomised, double-blind phase 3 trial.
Lancet Oncol. 2014 Oct;15(11):1195-206.
San-Miguel JF, Hungria VT, Yoon SS, Beksac M, Dimopoulos MA, Elghandour A, Jedrzejczak WW, Günther A, Nakorn TN, Siritanaratkul N, Corradini P, Chuncharunee S, Lee JJ, Schlossman RL, Shelekhova T, Yong K, Tan D, Numbenjapon T, Cavenagh JD, Hou J, LeBlanc R, Nahi H, Qiu L, Salwender H, Pulini S, Moreau P, Warzocha K, White D, Bladé J, Chen W, de la Rubia J, Gimsing P, Lonial S, Kaufman JL, Ocio EM, Veskovski L, Sohn SK, Wang MC, Lee JH, Einsele H, Sopala M, Corrado C, Bengoudifa BR, Binlich F, Richardson PG.
Panobinostat is a pan-deacetylase inhibitor. This study, called PANORAMA1, randomized 768 patients with relapsed/refractory multiple myeloma (s/p 1-3 previous treatment regimens) into two groups: the first one received bortezomib + dexamethasone + placebo (381), the second bortezomib + dexamethasone + panobinostat 20 mg PO on days 1, 3, 5, 8, 10, 12 (387 patients). Results showed a modest benefit from panobinostat:
  - Response rate: similar (55% with placebo, and 61% with panobinostat, p=0.09)
  - Rate of CR/nCR: 16% with placebo, and 28% with panobinostat (p<0.01)
  - Median progression-free survival (primary endpoint): 8.1 months with placebo, and 12 months with panobinostat
  - Median overall survival: similar (30.4 months with placebo, and 33.6 months with panobonostat, p=0.09; but median follow-up was approximately 6 months)

Oligoclonal and monoclonal bands after single autologous stem cell transplant in patients with multiple myeloma: impact on overall survival and progression-free survival.
Leuk Lymphoma. 2014 Oct;55(10):2284-9.
Jimenez-Zepeda VH, Reece DE, Trudel S, Franke N, Winter A, Chen C, Tiedemann R, Kukreti V.
Ninety-nine patients with myeloma evaluated at day 100 after an autologous stem cell transplant developed oligoclonal bands or monoclonal bands unrelated to the original clone. They had a favorable clinical outcome compared to the rest of the patients, with longer progression-free survival and overall survival.

Israeli-born offspring of Jewish immigrants of Middle Eastern origin have a lower incidence of multiple myeloma than those of European origin: a cohort study of 746 200 Israeli men followed from late adolescence.
Leuk Lymphoma. 2014 Oct;55(10):2290-5.
Leiba M, Afek A, Derazne E, Keinan-Boker L, Leiba A, Nagler A, Shamiss A, Kark JD.
This study supports the existence of a genetic component in the pathogenesis of multiple myeloma. Data from the Israeli National Cancer Registry showed that second generation man of Middle Eastern origin had a lower risk of developing myeloma compared to those of European origin.

Lenalidomide desensitization for delayed hypersensitivity reactions in 5 patients with multiple myeloma.
Br J Haematol. 2014 Oct;167(1):127-31.
Lee MJ, Wickner P, Fanning L, Schlossman R, Richardson P, Laubach J, Castells M.
Lenalidomide-associated rash occurs on approximately 27% of patients, and it is severe in 4-5% of cases. Other publications have shown desensitizations protocols for immediate hypersensitivity reactions, but this one illustrates 5 cases with delayed hypersensitivity reactions. The authors propose an interesting protocol that successfully accomplishes a slow desensitization in an outpatient basis over 6 weeks. For example: lenalidomide 2.5 mg x 1 for 1 week, 2.5 mg every 3 days x 3, 2.5 mg every 2 days x 3, 2.5 mg every day x 3, 2.5 mg alternating with 5 mg every day x 6, 5 mg every day x 6, 5 mg alternating with 10 mg every day x 6, and finally 10 mg  every day. 

Subclinical peripheral neuropathy in patients with multiple myeloma before chemotherapy is correlated with decreased fingertip innervation density.
J Clin Oncol. 2014 Oct 1;32(28):3156-62.
Kosturakis AK, He Z, Li Y, Boyette-Davis JA, Shah N, Thomas SK, Zhang H, Vichaya EG, Wang XS, Wendelschafer-Crabb G, Kennedy WR, Simone DA, Cleeland CS, Dougherty PM.
Quantitative sensory tests were obtained in 29 patients with newly diagnosed multiple myeloma, before the beginning of chemotherapy. The results showed that a very high percentage (>80%) of patients had a subclinical peripheral neuropathy, with decreased peripheral innervation density.

Lenalidomide-induced diarrhea in patients with myeloma is caused by bile acid malabsorption that responds to treatment.
Blood. 2014 Oct 9;124(15):2467-8.
Pawlyn C, Khan MS, Muls A, Sriskandarajah P, Kaiser MF, Davies FE, Morgan GJ, Andreyev HJ.
The authors evaluated 12 patients with myeloma who experienced significant diarrhea after therapy with lenalidomide. After testing with selenium homocholic acid taurine scanning, they believed the pathogenesis of the diarrhea was related to bile acid malabsorption. They treated patients with low-fat diet (20% or less of total calories) and a bile acid sequestrant (colesevelam 625 mg x6/day, with food and >4 hours after lenalidomide and other oral drugs). Diarrhea improved in all patients, and it resolved in 50% of them.

Aprepitant, Granisetron, and Dexamethasone for Prevention of Chemotherapy-Induced Nausea and Vomiting After High-Dose Melphalan in Autologous Transplantation for Multiple Myeloma: Results of a Randomized, Placebo-Controlled Phase III Trial.
J Clin Oncol. 2014 Oct 20;32(30):3413-20.
Schmitt T, Goldschmidt H, Neben K, Freiberger A, Hüsing J, Gronkowski M, Thalheimer M, Pelzl le H, Mikus G, Burhenne J, Ho AD, Egerer G.
In this study, 362 patients with multiple myeloma undergoing autologous stem cell transplant with high-dose melphalan were randomized to either granisetron + dexametasone + placebo (181 patients), or granisetron + dexamethasone + aprepitant (181 patients). Results favored the aprepitant group:
  - Absence of significant nausea within 120 hours of melphalan administration: 88% with placebo, and 94% with aprepitant
  - Absence of vomiting within 120 hours of melphalan administration: 65% with placebo, and 78% with aprepitant



Quantification of clonal circulating plasma cells in relapsed multiple myeloma.
Br J Haematol. 2014 Nov;167(4):500-5.
Gonsalves WI, Morice WG, Rajkumar V, Gupta V, Timm MM, Dispenzieri A, Buadi FK, Lacy MQ, Singh PP, Kapoor P, Gertz MA, Kumar SK.
Circulating plasma cells were quantified by multi-parameter flow cytometry in 647 patients with relapsed multiple myeloma. Circulating plasma cells were absent in patients in coimplete remission, whereas the presence of 100 or more circulating plasma cells (per 150,000 gated mononuclear events) was associated with an inferior median survival (12 months vs 33 months). The adverse impact on prognosis was maintained at multivariate analysis.

Older patients with myeloma derive similar benefit from autologous transplantation.
Biol Blood Marrow Transplant. 2014 Nov;20(11):1796-803.
Sharma M, Zhang MJ, Zhong X, Abidi MH, Akpek G, Bacher U, Callander NS, Dispenzieri A, Freytes CO, Fung HC, Gale RP, Gasparetto C, Gibson J, Holmberg LA, Kindwall-Keller TL, Klumpp TR, Krishnan AY, Landau HJ, Lazarus HM, Lonial S, Maiolino A, Marks DI, Mehta P, Mikhael Med JR, Nishihori T, Olsson R, Ramanathan M, Roy V, Savani BN, Schouten HC, Scott E, Tay J, To LB, Vesole DH, Vogl DT, Hari P.

International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma.
Lancet Oncol. 2014 Nov;15(12):e538-48 (Review).
Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, Kumar S, Hillengass J, Kastritis E, Richardson P, Landgren O, Paiva B, Dispenzieri A, Weiss B, LeLeu X, Zweegman S, Lonial S, Rosinol L, Zamagni E, Jagannath S, Sezer O, Kristinsson SY, Caers J, Usmani SZ, Lahuerta JJ, Johnsen HE, Beksac M, Cavo M, Goldschmidt H, Terpos E, Kyle RA, Anderson KC, Durie BG, Miguel JF.



Safety and tolerability of ixazomib, an oral proteasome inhibitor, in combination with lenalidomide and dexamethasone in patients with previously untreated multiple myeloma: an open-label phase 1/2 study.
Lancet Oncol. 2014 Dec;15(13):1503-12.
Kumar SK, Berdeja JG, Niesvizky R, Lonial S, Laubach JP, Hamadani M, Stewart AK, Hari P, Roy V, Vescio R, Kaufman JL, Berg D, Liao E, Di Bacco A, Estevam J, Gupta N, Hui AM, Rajkumar V, Richardson PG.
In this preliminary study involving 65 patients, very good partial response or better was observed in 58% of cases.



Giampaolo Talamo, MD