Véronique Leblond

Baseline differential blood count and prognosis in CD20-positive post-transplant lymphoproliferative disorder in the prospective PTLD-1 trial.

Baseline differential blood count and prognosis in CD20-positive post-transplant lymphoproliferative disorder in the prospective PTLD-1 trial

Effectiveness of second-line treatment in AL amyloidosis patient's refractory to M-Dex.

Oral melphalan and dexamethasone (MDex) is now widely considered to be the standard conventional treatment for patients with AL amyloidosis. With M-Dex median survival is around 5 years but survival of non-responders is poor in the absence of rescue treatment. We examined whether utilization of new drugs in non-responders to M-Dex is associated with an improved survival. We included 32 patients who received, as salvage therapy, thalidomide (n1⁄4 5), lenalidomide (n1⁄4 7), or bortezomib (n1⁄4 20). Hematological response occurred in 71%, with 34% complete response (CR). Partial response was obtained in 4/5 patients with thalidomide and 2/7 with lenalidomide; 17/20 patients (85%) in the bortezomib group responded with 11 CR (55%). With a median follow-up of 21 months, 23 patients (72%) are alive. Introduction of new drugs in refractory patients to MDex gives a high level of response leading to a better survival. Bortezomib seems to be particularly attractive with response rate of 85%, and 55% CR. Introduction: Since the randomized trial published in 2007 [1] comparing intensive treatment with stem cell support (melphalan 140 or 200 mg/m depending on age and clinical status supported with autologous stem cell transplant (ASCT) collected with granulocyte colony-stimulating factor (G-CSF) alone) and the oral regimen melphalan and dexamethasone (MDex) (melphalan 10 mg/m and dexamethasone 40 mg for 4 days each months, up to 18 months), M-Dex is our reference front-line therapy in patients with AL whatever be the risk group. With M-Dex, median survival is longer than with MP (melphalan and prednisone), being around 5 years, in our study as well as in the Italian series [2]. Patients with hematologic response (at least 50% drop in the monoclonal protein) after M-Dex have a very good median survival but survival was very poor for refractory patients in our study. The 12 nonresponder patients in the M-Dex arm (patients who received at least three cycles of M-Dex and had a measurable disease) had a median survival of only 6 months (Figure 1), in the absence of valuable rescue treatment between 2000 and 2005. The new drugs used in myeloma, thalidomide, lenalidomide, and bortezomib have been reported to be effective in patients with AL amyloidosis [3–8]. We examined whether utilization of these drugs in patients refractory to M-Dex has translated into improved outcome. Method: We performed a retrospective multicentric study in 11 centers belonging to the French network for AL amyloidosis. Patients with AL amyloidosis, treated front line with M-Dex, since June 2006 were included if they were considered as refractory by their referent physician and had received, as salvage treatment, thalidomide, lenalidomide, or bortezomib, associated to sequential dexamethasone and/or alkylating agents. We recorded the hematological response, monitored by the free light chain (FLC) assay, with second-line treatment. All patients but one enrolled in this study had measurable disease, only one patient had a monoclonal light chain level below 30 mg/l with an abnormal serum-free light chain ratio, he was considered as non-responder after the second-line treatment and normalized the ratio after third-line treatment with bortezomib and dexamethasone. Survival was analyzed from the first day Figure 1. Randomized trial (high-dose melphalan versus melphalan plus dexamethasone), 2000–2005 [1]. Survival according to the hematologic response in the 38 patients in the M-Dex arm who could be evaluated. Blue curve: patients with at least a 50% response. Red curve: patients with less than a 50% response, median survival: 6 months. 145

Treatment Recommendations in Waldenström Macroglobulinemia

Waldenstrom’s macroglobulinemia (WM) is a distinct B-cell lymphoproliferative disorder for which clearly defined criteria for the diagnosis, initiation of therapy, and treatment strategy have been proposed as part of the consensus panels of the International Workshops on WM (IWWM). Therapeutic strategies in WM should be based on individual patient and disease characteristics. Chemoimmunotherapy combinations with rituximab (R) and cyclophosphamide/dexamethasone (DRC) or bendamustine (Benda-R) or bortezomib/dexamethasone (BDR) provide durable responses and are still indicated in most patients. The approval of the BTK-inhibitor ibrutinib in the USA and in Europe represents a novel and effective treatment option for both treatment-naive and relapsing patients. Other BCR inhibitors, second-generation proteasome inhibitors (e.g., carfilzomib), and mTOR inhibitors are promising and may expand future treatment options. This chapter summarizes the treatment strategies in WM patients with the treatment options widely described by previous authors.

Laboratory Investigations and Findings: Hematological Abnormalities, Biochemical Investigations, Free Light and Heavy Chains

Waldenstrom macroglobulinemia (WM) is a distinct B-cell lymphoproliferative disorder characterized by bone marrow infiltration of lymphoplasmacytic cells along with production of an IgM monoclonal protein in the serum. It can be associated to various complications related to tumor infiltration or to the serum monoclonal component.