1.Differential effects of lenalidomide during plasma cell differentiation.
Jourdan M1,2, Cren M1, Schafer P3, Robert N4, Duperray C5, Vincent L6, Ceballos P6, Cartron G6,7, Rossi JF6,7, Moreaux J2,4,7, Chopra R3, Klein B2,4,7. Oncotarget. 2016 Apr 4. doi: 10.18632/oncotarget.8581. [Epub ahead of print]
Thalidomide, lenalidomide and pomalidomide have greatly improved the outcome of patients with multiple myeloma. However, their effects on plasma cells, the healthy counterpart of myeloma cells, are unknown. Here, we investigated lenalidomide effects on normal human plasma cell generation using an in vitro model. Lenalidomide inhibited the generation of pre-plasmablasts and early plasma cells, while it moderately affected plasmablast production. It also reduced the expression level of Ikaros, Aiolos, and IRF4 transcription factors, in plasmablasts and early plasma cells. This suggests that their differential sensitivity to lenalidomide is not due to a difference in Ikaros or Aiolos degradation. Lenalidomide also inhibited long-lived plasma cell generation, but did not impair their long-term survival once generated. This last observation is in agreement with the finding that lenalidomide treatment for 3-18 months did not affect the bone marrow healthy plasma cell count in allografted patients with multiple myeloma.
2.Treatment of relapsed and refractory multiple myeloma.
Sonneveld P1, Broijl A2. Haematologica. 2016 Apr;101(4):396-406. doi: 10.3324/haematol.2015.129189.
The approach to the patient with relapsed or relapsed/refractory multiple myeloma (RRMM) requires a careful evaluation of the results of previous treatments, the toxicities associated with them and an assessment of prognostic factors. Since the majority of patients will have received prior therapy with drug combinations including a proteasome inhibitor and/or an immunomodulatory drug (IMiD), it is the physician's task to choose the right moment for the start of therapy and define with the patient which goals need to be achieved. The choice of regimen is usually based on prior responsiveness, drugs already received, prior adverse effects, the condition of the patient and expected effectiveness and tolerability. Many double and triple drug combinations are available. In addition, promising new drugs like pomalidomide, carfilzomib and monoclonal antibodies are, or will be, available shortly, while other options can be tried in clinical studies.
3.Safety and tolerability of pomalidomide-based regimens (pomalidomide-carfilzomib-dexamethasone with or without cyclophosphamide) in relapsed/refractory multiple myeloma and severe renal dysfunction: a case series.
Richter J1, Biran N1, Duma N1, Vesole DH1, Siegel D1. Hematol Oncol. 2016 Mar 27. doi: 10.1002/hon.2290. [Epub ahead of print]
Renal dysfunction negatively impacts outcomes in patients with multiple myeloma (MM). Few treatment options are currently available for patients with MM and comorbid renal dysfunction, and as they are generally excluded from clinical trials, data on the use of immunomodulatory drugs in this population are scarce. In this paper, we describe a case series of five women with MM and severe renal dysfunction or dialysis dependency who were refractory to both bortezomib and either lenalidomide or thalidomide and were treated with full-dose (4 mg) pomalidomide. As part of their treatment regimen, these patients also received carfilzomib and dexamethasone with or without cyclophosphamide. All five patients achieved at least a partial response to pomalidomide-based therapy, which was relatively well tolerated. Our findings suggest that pomalidomide may represent a valuable and tolerable treatment option for MM patients with severe renal impairment.
4.Analysis of renal impairment in MM-003, a phase 3 study of pomalidomide + low-dose dexamethasone vs high-dose dexamethasone in refractory or relapsed and refractory multiple myeloma.
Weisel KC1, Dimopoulos MA2, Moreau P3, Lacy MQ4, Song KW5, Delforge M6, Karlin L7, Goldschmidt H8, Banos A9, Oriol A10, Alegre A11, Chen C12, Cavo M13, Garderet L14, Ivanova V15, Martinez-Lopez J16, Knop S17, Yu X18, Hong K18, Sternas L18, Jacques C18, Za Haematologica. 2016 Apr 14. pii: haematol.2015.137083. [Epub ahead of print]
Pomalidomide + low-dose dexamethasone is effective and well tolerated for refractory or relapsed and refractory multiple myeloma after bortezomib and lenalidomide failure. The phase 3 trial MM-003 compared pomalidomide + low-dose dexamethasone with high-dose dexamethasone. This subanalysis grouped patients by baseline creatinine clearance ≥ 30 - < 60 mL/min (n = 93, pomalidomide + low-dose dexamethasone; n = 56, high-dose dexamethasone) or ≥ 60 mL/min (n = 205, pomalidomide + low-dose dexamethasone; n = 93, high-dose dexamethasone). Median progression-free survival was similar for both subgroups and favored pomalidomide + low-dose dexamethasone vs high-dose dexamethasone: 4.0 vs 1.9 months in the group with baseline creatinine clearance ≥ 30 - < 60 mL/min (P < .001) and 4.0 vs 2.0 months in the group with baseline creatinine clearance ≥ 60 mL/min (P < .001). Median overall survival for pomalidomide + low-dose dexamethasone vs high-dose dexamethasone was 10.
