Bortezomib alternating with dexamethasone is a highly effective induction regimen with low toxicity. The kinetic study has shown a high degree of heterogeneity in response and rapid effect from both agents, supporting the use of a short induction regimen before ASCT in MM.

A 64-year-old man presented with a persistent cough. His past medical history included COVID-19 pneumonia one month previously. On admission, a full blood count showed a haemoglobin concentration of 120 g/l, a platelet count of 98 9 10 9 /l and a leukocyte count of 44 9 10 9 /l. A peripheral blood film showed 80% atypical lymphoid cells. Many of the abnormal cells had deeply basophilic cytoplasm with a markedly irregular nuclear contour producing a petal-shaped nucleus, mimicking the flower cells of adult T-cell leukaemia/lymphoma (ATLL) (all images; May-Gr€ unwald-Giemsa stain, 9100 objective), while other atypical cells showed either bilobed or rounded nuclei.Flow cytometric analysis showed strong expression of CD38, CD56 and CD138 with no expression of CD3, CD4, CD7, CD8, CD19, CD20, CD25 or CD45. Serum calcium was normal. Serum protein electrophoresis and immunofixation showed a lambda monoclonal component (12 g/l) with lambda-free light chains being quantified at 42.9 g/l. Antibodies to the human T-cell lymphotropic virus-1 (HTLV-1) were not detected. A diagnosis of primary plasma cell leukaemia was made.A bone marrow aspirate film was hypercellular with 95% abnormal plasma cells. Cytogenetic analysis showed a complex karyotype: 42,X,ÀY,add(1)(q?),+del(1)(p21),del(2) (q32),À5,À10,del(11)(q23),À12,À13,add(14)(q32) [16]/46,XY [9]. Fluorescence in situ hybridisation (FISH) analysis showed deletion of RB1 and LAMP1 on 13q, t(4;14) (IGH/ FGFR3 rearrangement) and amp(1q21).Plasma cell leukaemia rarely presents with flower-shaped nuclei. A differential diagnosis of ATLL should be considered in these cases, especially in HTLV-1 endemic areas.

Dexamethasone-based combinations have been the standard induction regimens in younger patients with multiple myeloma (MM) prior to stem cell transplantation. Bortezomib alone or in association with dexamethasone has shown significant activity in patients with both refractory/relapsed and newly diagnosed MM. We investigated the efficacy of bortezomib and dexamethasone administered on an alternating basis, the end-points of the study being response rate, kinetics of response, safety, stem cell mobilization and response postransplant. Patients with newly diagnosed MM under the age of 66 years and with adequate organ and function status were eligible. Patients were treated with bortezomib 1.3 mg/m2 on days 1, 4, 8 and 11 (cycles 1, 3, 5) and dexamethasone 40 mg p.o. on days 1–4, 9–12 and 17–20 (cycles 2, 4 and 6), followed by high dose-therapy intensification (HDT) with melphalan -200. Responses were evaluated by the EBMT criteria but a near-CR (n-CR) response category was included. Stem cell mobilization was performed after G-CSF priming. Between August, 2005 and March, 2006, 40 patients (18 M, 22F, median age 57 yrs) were enrolled. The M-protein type was IgG in 26 patients, IgA in 11 and light chain in 3. Six patients had extramedullary plasmacytomas. At the time of this analysis response data after the 6 cycles were available for 26 of the 40 patients. The overall response rate was 76% and the CR rate 15% (4 CR, 5 n-CR, 7 PR, 4 MR, 2 stable disease, 3 progressive disease, 1 non-evaluable because of treatment discontinuation due to toxicity after cycle 1). In patients who achieved at least PR the mean M-protein decrease was 84% (48% associated with bortezomib cycles and 36% with dexamethasone). Two responding patients showed disease progression immediately before HDT. In all thirteen patients mobilized to date stem cells could be adequately collected (median CD34+ cells: 4.85 x106/Kg; range 2–10.6) with only one apheresis. Toxicity was low and mainly consisted of grade 1 and 2 neutropenia, fever, GI symptoms, fatigue, peripheral neuropathy and thrombocytopenia. Ten (25%) patients developed mild peripheral neuropathy (grade 1=9 cases; grade 2=1 case) and 11 patients grade 1 thrombocytopenia. Grade 3 toxicity was only observed in 7 patients (neutropenia 6, skin/liver 1 case) and no patient developed grade 4 toxicity. Updated results on all patients along with cytogenetic data will be presented at the meeting. In conclusion, bortezomib alternating with dexamethasone is highly effective as up-front therapy in patients with MM, is associated with an extremely low toxicity and results in an excellent stem cell harvesting. The results of this trial support a short program of alternating bortezomib and dexamethasone as an effective and safe induction regimen for newly diagnosed younger myeloma patients.

Background: Over the last decade there has been an improvement on the outcome of multiple myeloma (MM) patients. In patients eligible for high-dose chemotherapy and autologous stem cell transplant (ASCT), the inclusion of bortezomib in induction chemotherapy (ICT) has significantly delayed disease progression. Several studies have shown that achieving a complete response (CR) after ASCT is a predictive factor for disease control, leading to improved progression-free survival (PFS) and overall survival (OS). Aims: Assessing the impact of depth of response before and after ASCT on PFS in a population of MM patients treated with ICT including bortezomib and identifying predictive/protective factors for disease progression. Methods: Retrospective study of MM patients admitted for ASCT between January 2015 and December 2017 treated in first line with VCd (bortezomib, cyclophosphamide, and dexamethasone) or VTd (bortezomib, thalidomide and dexamethasone). Demographic (gender, age), clinical and biological variables at diagnosis were collected, as well as response obtained before and at D+100 after ASCT, and time elapsed between ASCT and disease progression. Statistical analysis was performed using STATA software (V13). Results: A total of 53 MM patients in the first line setting were included in this study. 43.4% were male; median age at diagnosis was 60 years old (IQR, 40-72). Both groups (VCd and VTd) had similar baseline characteristics. Median follow-up after induction chemotherapy was 20.6 months. PFS of patients who achieved CR or very good partial response (VGPR) post-induction was 73.7%, versus 60% in patients who achieved partial response (PR) or lower (log-rank p = 0.07). Looking at different variables that could modify the time between ASCT and disease progression, we observed that ISS stage 3 is an independent predictive factor for disease progression (HR 3.1; p = 0.014), and obtaining CR/ VGPR at D+100 post-ASCT is an independent protective factor against disease progression (HR 0.2; p = 0.004). Summary/Conclusion: Despite the relatively short follow-up period, in this population of transplant-eligible MM patients, we have demonstrated that the depth of response after induction chemotherapy (VGPR/CR) is critical for a greater PFS, and that a profound reduction in tumor burden (VGPR/CR) after ASCT allows for prolonged disease control. However, ISS stage 3 is a risk factor for disease progression regardless of the obtained response.

cohort, suggesting potential overlap with immunodeficiency seen with CLL/SLL pts. Most surprisingly is the high rate of infusion related reactions; however, these were mainly confined to grade 2 reactions and grade 3 reactions were much lower than in the CLL11 trial (Goede V, NEJM 2014). While PFS is shorter compared to CLL11, this reflects both pts not completing therapy, as well as including pts in the r/r setting. Regardless, OBI remains an effective and well tolerated agent in both frontline and r/r pts with CLL/SLL who may not be eligible for other therapies.ABSTRACT 379