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© 2020 by American Society of Clinical Oncology., [Purpose]: Maintenance therapy prolongs progression-free survival (PFS) in patients with newly diagnosed multiple myeloma (NDMM) not undergoing autologous stem cell transplantation (ASCT) but has generally been limited to immunomodulatory agents. Other options that complement the induction regimen with favorable toxicity are needed., [Patients and Methods]: The phase III, double-blind, placebo-controlled TOURMALINE-MM4 study randomly assigned (3:2) patients with NDMM not undergoing ASCT who achieved better than or equal to partial response after 6-12 months of standard induction therapy to receive the oral proteasome inhibitor (PI) ixazomib or placebo on days 1, 8, and 15 of 28-day cycles as maintenance for 24 months. The primary endpoint was PFS since time of randomization., [Results]: Patients were randomly assigned to receive ixazomib (n = 425) or placebo (n = 281). TOURMALINE-MM4 met its primary endpoint with a 34.1% reduction in risk of progression or death with ixazomib versus placebo (median PFS since randomization, 17.4 v 9.4 months; hazard ratio [HR], 0.659; 95% CI, 0.542 to 0.801; P < .001; median follow-up, 21.1 months). Ixazomib significantly benefitted patients who achieved complete or very good partial response postinduction (median PFS, 25.6 v 12.9 months; HR, 0.586; P < .001). With ixazomib versus placebo, 36.6% versus 23.2% of patients had grade ≥ 3 treatment-emergent adverse events (TEAEs); 12.9% versus 8.0% discontinued treatment because of TEAEs. Common any-grade TEAEs included nausea (26.8% v 8.0%), vomiting (24.2% v 4.3%), and diarrhea (23.2% v 12.3%). There was no increase in new primary malignancies (5.2% v 6.2%); rates of on-study deaths were 2.6% versus 2.2%., [Conclusio]:Ixazomib maintenance prolongs PFS with no unexpected toxicity in patients with NDMM not undergoing ASCT. To our knowledge, this is the first PI demonstrated in a randomized clinical trial to have single-agent efficacy for maintenance and is the first oral PI option in this patient population., This study was sponsored by Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. T

Background/Aim: Primary mediastinal large Bcell lymphoma (PMLBCL) is an aggressive B-cell non- Hodgkin lymphoma (NHL), whose prognosis has greatly improved since the incorporation of the anti-CD20 monoclonal antibody rituximab into current therapeutic regimens. Evidence, however, on the optimal time interval between consecutive chemoimmunotherapy (CIT) cycles is still scarce. This study aimed to evaluate the efficacy outcomes of the more commonly administered 3-weekly regimens to the biweekly ones in a PMLBCL patients' population, who were mostly treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone every 21 days (R-CHOP-21) or R-CHOP-14. Patients and Methods: We retrospectively studied our cohort of consecutively treated PMLBCL patients, focusing on their treatment density, in order to determine possible differences in treatment outcomes. Results: CIT, in the form of both RCHOP- 21 as well as R-CHOP-14 (or similar regimens), is highly active in PMLBCL, with low rates of early treatment failure. In our cohort of patients, R-CHOP-14 did not result in a meaningful improvement of freedom from progression (FFP) or overall survival (OS). Conclusion: Both R-CHOP- 14 and R-CHOP-21 are probably equally effective in PMLBCL, yet further, prospective, randomized studies are warranted to clarify whether dose-dense regimens can be associated with better disease control and long-term results. © 2022 International Institute of Anticancer Research. All rights reserved.

Herein we present a rare case of two brothers diagnosed with CML four years apart. Importantly, our case of CML occurrence among siblings is the fifth one reported and the second one investigated by both, conventional cytogenetics and RT-PCR analysis. Moreover, although Ph chromosome was detected in both our patients, RT-PCR revealed the presence of two different BCR-ABL transcripts. Finally, both our patients have been followed for a long period of time offering thus the opportunity to observe the differences in the clinical course. © 2021 The Authors

The “POWERFUL” multicenter, retrospective, and prospective study investigated the effectiveness of pomalidomide plus low‐dose dexamethasone (POM/LoDex) therapy in relapsed/re-fractory multiple myeloma in routine care in Greece. Ninety‐nine eligible adult patients treated with POM/LoDex according to the approved label after having received ≥2 prior therapies, including lenalidomide and bortezomib, were consecutively enrolled between 16 November 2017 and 21 Feb-ruary 2019 in 18 hematology departments. Fifty patients (50.5%) started POM/LoDex as third‐line treatment. During the treatment period (median: 8.3 months; range: 0.3–47.6 months), the median POM dose was 4 mg/day, and 31.3% of the patients received additional antimyeloma agents. The overall response rate was 32.3%. During a median follow‐up period of 13.8 months (Kaplan–Meier estimate), the median progression‐free survival (PFS) was 10.5 months (95% CI: 7.4–14.4). The PFS was not significantly different between patients receiving POM/LoDex in the third versus later line of therapy, nor between patients receiving concomitant antimyeloma therapy versus POM/LoDEx doublet. During the prospective safety data collection period (median: 7.6 months) among patients with prospective follow‐up (N = 75), POM‐related adverse event incidence rate was 42.7% (serious: 18.7%; grade ≥ 3 hematological POM‐related adverse events: 8.0%). Only neutropenia (13.3%) was reported at a frequency ≥10%. In conclusion, in this real‐world study, POM/LoDex displayed a long PFS with no new safety signals emerging. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Carfilzomib with dexamethasone (Kd) is a well-established regimen for the treatment of relapsed/refractory multiple myeloma (RRMM). There is limited information for the effects of Kd on myeloma-related bone disease. This non-interventional study aimed to assess skeletal-related events (SREs) and bone metabolism in patients with RRMM receiving Kd, in the absence of any bone-targeted agent. Twenty-five patients were enrolled with a median of three prior lines of therapy; 72% of them had evidence of osteolytic bone disease at study entry. During Kd treatment, the rate of new SREs was 28%. Kd produced a clinically relevant (≥30%) decrease in C-telopeptide of collagen type-1 (p = 0.048) and of tartrate-resistant acid phosphatase-5b (p = 0.002) at 2 months. This reduction was at least partially due to the reduction in the osteoclast regulator RANKL/osteoprotegerin ratio, at 2 months (p = 0.026). Regarding bone formation, there was a clinically relevant increase in osteocalcin at 6 months (p = 0.03) and in procollagen type I N-propeptide at 8 months post-Kd initiation. Importantly, these bone metabolism changes were independent of myeloma response to treatment. In conclusion, Kd resulted in a low rate of SREs among RRMM patients, along with an early, sustained and clinically relevant decrease in bone resorption, which was accompanied by an increase in bone formation, independently of myeloma response and in the absence of any bone-targeted agent use. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

End-of-treatment (EoT) PET/CT is used as a guide to omit radiotherapy (RT) patients with primary mediastinal large B-cell lymphoma (PMBCL). We present the mature and extended results of a retrospective study evaluating the prognostic significance of EoT-PET/CT after adequate response to R-CHOP. Among 231 consecutive PMLBCL patients, 182 underwent EoT-PET/CT and were evaluated according to the Deauville 5-point scale (D5PS) criteria. Freedom from progression (FFP) was measured from the time of PET/CT examination. Among 182 patients, 72 (40%) had D5PS score 1 (D5PSS-1), 33 (18%) had 2, 28 (15%) had 3, 29 (16%) had 4, and 20 (11%) had 5. The 5-year FFP was 97, 94, 92, 82, and 44% for D5PSS-1, D5PSS-2, D5PSS-3, D5PSS-4, and D5PSS-5, respectively. Among 105 patients with unequivocally negative PET/CT (D5PSS-1/D5PSS-2), 49 (47%) received RT (median dose 3420 cGy) and 56 (53%) did not with relapses in 0/49 vs. 4/56 patients (2 mediastinum and 2 isolated CNS relapses).The 5-year FFP for those who received RT or not was 100% versus 96%, when isolated CNS relapses were censored (p = 0.159). Among D5PSS-3 patients (27/28 irradiated-median dose 3600 cGy), the 5-year FFP was 92%. The 5-year FFP for D5PSS-4 and D5PSS-5 was 82 and 44%; 44/49 patients received RT (median dose 4000 and 4400 cGy for D5PSS-4 and D5PSS-5). Our study supports the omission of RT in a sizeable fraction of PET/CT-negative patients and definitely discourages salvage chemotherapy and ASCT in patients with PMLBCL who conventionally respond to R-CHOP, solely based on PET/CT positivity in the absence of documented progressive or multifocal disease. The persistence of positive PET/CT with D5PSS < 5 after consolidative RT should not trigger the initiation of further salvage chemotherapy in the absence of conventionally defined PD. © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.

Purpose: The investigation of a semi-quantitative index in the pelvis to assess for diffuse bone marrow (BM) [18F]-FDG uptake and the investigation of PET skeletal patterns in multiple myeloma (MM) patients, in accordance with prognostic markers, clonal plasma cell (cPC) morphology, and response to therapy. Methods: We prospectively analyzed [18F]-FDG PET/CT in 90 MM patients (newly diagnosed, 60; relapsed/refractory, 30). Among other PET/CT parameters, we calculated the ratio SUVmax pelvis/liver and examined for correlations with known MM prognostic parameters, cPC morphology (good vs. low/intermediate differentiation), and response to therapy. Results: SUVmax pelvis/liver ratio was significantly lower for the group of good differentiation vs. intermediate/low differentiation cPCs (p < 0.001) and showed a positive correlation with BM infiltration rate, β2 microglobulin, serum ferritin, international staging system (ISS), and revised ISS; no significant correlation was found with hemoglobin. A cutoff value of 1.1 showed an excellent specificity (99%) and high sensitivity (76%) for diffuse BM involvement (AUC 0.94; p < 0.001). Mixed pattern and appendicular involvement correlated with poor prognostic features while normal pattern, found in 30% of patients, correlated with good prognostic features. Presence of ≥ 10 focal lesions negatively predicted for overall response (p < 0.05; OR 4.8). The CT component improved the diagnostic performance of PET. Conclusion: This study showed, for the first time, that cPC morphology and markers related with MM biology, correlate with SUVmax pelvis/liver index, which could be used as a surrogate marker for BM assessment and disease prognosis; PET patterns correlate with MM prognostic features and response rates. © 2020, Springer-Verlag GmbH Germany, part of Springer Nature.

Transplant-ineligible relapsed/refractory (rr) diffuse large B-cell lymphoma (DLBCL) patients represent an unmet medical need. Polatuzumab vedotin (Pola), an anti-CD79b antibody-drug-conjugate (ADG), with bendamustine- rituximab(BR) has recently gained approval for these patients, both in the USA and Europe, based on the GO29365 phase IIb trial. Real-life data with Pola are extremely limited. We report the outcomes of 61 Greek patients, who received Pola-(B)R mainly within a compassionate use program. Treatment was given for up to six 21-day cycles. Bendamustine was omitted in three cases due to previous short-lived responses. Fourty-nine rrDLBCL(efficacy cohort-EC) and 58 rr aggressive B-NHL (safety cohort-SC) patients received at least 1 Pola-BR cycle. Twenty-one (43%) patients of the EC responded with 12/49 (25%) CR and 9/49 (18%) PR as best response. Median progression–free survival, overall survival and duration of response were 4.0, 8.5, and 8.5 months respectively, while 55% of patients experienced a grade ≥3 adverse event, mainly hematologic. Treatment discontinuations and death during treatment were mainly due to disease progression. Twenty-two (41%) patients received further treatment; 11/22 are still alive, including one after CAR-T cells, and two after stem cell transplantation. Our data confirm that Pola-BR is a promising treatment for rrDLBCL patients, inducing an adequate response rate with acceptable toxicity. Pola-BR could be used as bridging therapy before further consolidative treatments. © 2021 John Wiley & Sons Ltd.

Background: In a phase 1b study, intravenous daratumumab plus pomalidomide and dexamethasone induced a very good partial response or better rate of 42% and was well tolerated in patients with heavily pretreated multiple myeloma. We aimed to evaluate whether daratumumab plus pomalidomide and dexamethasone would improve progression-free survival versus pomalidomide and dexamethasone alone in patients with previously treated multiple myeloma. Methods: In this ongoing, open-label, randomised, phase 3 trial (APOLLO) done at 48 academic centres and hospitals across 12 European countries, eligible patients were aged 18 years or older, had relapsed or refractory multiple myeloma with measurable disease, had an Eastern Cooperative Oncology Group performance status of 0–2, had at least one previous line of therapy, including lenalidomide and a proteasome inhibitor, had a partial response or better to one or more previous lines of antimyeloma therapy, and were refractory to lenalidomide if only one previous line of therapy was received. Patients were randomly assigned (1:1) by an interactive web-response system in a random block size of two or four to receive pomalidomide and dexamethasone alone or daratumumab plus pomalidomide and dexamethasone. Randomisation was stratified by number of previous lines of therapy and International Staging System disease stage. All patients received oral pomalidomide (4 mg, once daily on days 1–21) and oral dexamethasone (40 mg once daily on days 1, 8, 15, and 22; 20 mg for those aged 75 years or older) at each 28-day cycle. The daratumumab plus pomalidomide and dexamethasone group received daratumumab (1800 mg subcutaneously or 16 mg/kg intravenously) weekly during cycles 1 and 2, every 2 weeks during cycles 3–6, and every 4 weeks thereafter until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival in the intention-to-treat population. Safety was analysed in all patients who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov, NCT03180736. Findings: Between June 22, 2017, and June 13, 2019, 304 patients (median age 67 years [IQR 60–72]; 161 [53%] men and 143 [47%] women) were randomly assigned to the daratumumab plus pomalidomide and dexamethasone group (n=151) or the pomalidomide and dexamethasone group (n=153). At a median follow-up of 16·9 months (IQR 14·4–20·6), the daratumumab plus pomalidomide and dexamethasone group showed improved progression-free survival compared with the pomalidomide and dexamethasone group (median 12·4 months [95% CI 8·3–19·3] vs 6·9 months [5·5–9·3]; hazard ratio 0·63 [95% CI 0·47–0·85], two-sided p=0·0018). The most common grade 3 or 4 adverse events were neutropenia (101 [68%] of 149 patients in the daratumumab plus pomalidomide and dexamethasone group vs 76 [51%] of 150 patients in the pomalidomide and dexamethasone group), anaemia (25 [17%] vs 32 [21%]), and thrombocytopenia (26 [17%] vs 27 [18%]). Serious adverse events occurred in 75 (50%) of 149 patients in the daratumumab plus pomalidomide and dexamethasone group versus 59 (39%) of 150 patients in the pomalidomide and dexamethasone group; pneumonia (23 [15%] vs 12 [8%] patients) and lower respiratory tract infection (18 [12%] vs 14 [9%]) were most common. Treatment-emergent deaths were reported in 11 (7%) patients in the daratumumab plus pomalidomide and dexamethasone group versus 11 (7%) patients in the pomalidomide and dexamethasone group. Interpretation: Among patients with relapsed or refractory multiple myeloma, daratumumab plus pomalidomide and dexamethasone reduced the risk of disease progression or death versus pomalidomide and dexamethasone alone and could be considered a new treatment option in this setting. Funding: European Myeloma Network and Janssen Research and Development. © 2021 Elsevier Ltd

Background: Selinexor combined with dexamethasone has shown activity in patients with heavily pre-treated multiple myeloma. In a phase 1b/2 study, the combination of oral selinexor with bortezomib (a proteasome inhibitor) and dexamethasone induced high response rates with low rates of peripheral neuropathy, the main dose-limiting toxicity of bortezomib. We aimed to evaluate the clinical benefit of weekly selinexor, bortezomib, and dexamethasone versus standard bortezomib and dexamethasone in patients with previously treated multiple myeloma. Methods: This phase 3, randomised, open-label trial was done at 123 sites in 21 countries. Patients aged 18 years or older, who had multiple myeloma, and who had previously been treated with one to three lines of therapy, including proteasome inhibitors, were randomly allocated (1:1) to receive selinexor (100 mg once per week), bortezomib (1·3 mg/m2 once per week), and dexamethasone (20 mg twice per week), or bortezomib (1·3 mg/m2 twice per week for the first 24 weeks and once per week thereafter) and dexamethasone (20 mg four times per week for the first 24 weeks and twice per week thereafter). Randomisation was done using interactive response technology and stratified by previous proteasome inhibitor therapy, lines of treatment, and multiple myeloma stage. The primary endpoint was progression-free survival in the intention-to-treat population. Patients who received at least one dose of study treatment were included in the safety population. This trial is registered at ClinicalTrials.gov, NCT03110562. The trial is ongoing, with 55 patients remaining on randomised therapy as of Feb 20, 2020. Findings: Of 457 patients screened for eligibility, 402 were randomly allocated—195 (49%) to the selinexor, bortezomib, and dexamethasone group and 207 (51%) to the bortezomib and dexamethasone group—and the first dose of study medication was given between June 6, 2017, and Feb 5, 2019. Median follow-up durations were 13·2 months [IQR 6·2–19·8] for the selinexor, bortezomib, and dexamethasone group and 16·5 months [9·4–19·8] for the bortezomib and dexamethasone group. Median progression-free survival was 13·93 months (95% CI 11·73–not evaluable) with selinexor, bortezomib, and dexamethasone and 9·46 months (8·11–10·78) with bortezomib and dexamethasone (hazard ratio 0·70 [95% CI 0·53–0·93], p=0·0075). The most frequent grade 3–4 adverse events were thrombocytopenia (77 [39%] of 195 patients in the selinexor, bortezomib, and dexamethasone group vs 35 [17%] of 204 in the bortezomib and dexamethasone group), fatigue (26 [13%] vs two [1%]), anaemia (31 [16%] vs 20 [10%]), and pneumonia (22 [11%] vs 22 [11%]). Peripheral neuropathy of grade 2 or above was less frequent with selinexor, bortezomib, and dexamethasone (41 [21%] patients) than with bortezomib and dexamethasone (70 [34%] patients; odds ratio 0·50 [95% CI 0·32–0·79], p=0·0013). 47 (24%) patients in the selinexor, bortezomib, and dexamethasone group and 62 (30%) in the bortezomib and dexamethasone group died. Interpretation: A once-per-week regimen of selinexor, bortezomib, and dexamethasone is a novel, effective, and convenient treatment option for patients with multiple myeloma who have received one to three previous lines of therapy. Funding: Karyopharm Therapeutics. © 2020 Elsevier Ltd

Real-world data on regimens for relapsed/refractory multiple myeloma (RRMM) represent an important component of therapeutic decision-making. This multi-centric, retrospective, observational study conducted by the treating physicians evaluated the effectiveness and safety of ixazomib-lenalidomide-dexamethasone (IRd) in 155 patients who received ixazomib via early access programs in Greece, the UK, and the Czech Republic. Median age was 68 years; 17% had an Eastern Cooperative Oncology Group performance status ≥ 2; median number of prior therapies was 1 (range 1–7); 91%, 47%, and 17% had received prior bortezomib, thalidomide, and lenalidomide, respectively. Median duration of exposure to ixazomib was 9.6 months. Overall response rate was 74%, including 35% very good partial response or better (16% complete response). Median progression-free survival (PFS) was 27.6 months (27.6 and 19.9 months in patients with 1 or > 1 prior lines, respectively). IRd treatment for ≥ 6 months was associated with longer PFS (hazard ratio 0.06). Fourteen patients (9%) discontinued IRd due to adverse events/toxicity in the absence of disease progression. Peripheral neuropathy was reported in 35% of patients (3% grades 3–4). These findings support the results of the phase III TOURMALINE-MM1 trial in a broader real-world RRMM population. © 2020, Springer-Verlag GmbH Germany, part of Springer Nature.

We investigated incidence, characteristics and outcome of patients with macrofocal multiple myeloma (MFMM) treated mainly with novel therapies. Based on definition (BMPCs

PURPOSE Maintenance therapy prolongs progression-free survival (PFS) in patients with newly diagnosed multiple myeloma (NDMM) not undergoing autologous stem cell transplantation (ASCT) but has generally been limited to immunomodulatory agents. Other options that complement the induction regimen with favorable toxicity are needed. PATIENTS AND METHODS The phase III, double-blind, placebo-controlled TOURMALINE-MM4 study randomly assigned (3:2) patients with NDMM not undergoing ASCT who achieved better than or equal to partial response after 6-12 months of standard induction therapy to receive the oral proteasome inhibitor (PI) ixazomib or placebo on days 1, 8, and 15 of 28-day cycles as maintenance for 24 months. The primary endpoint was PFS since time of randomization. RESULTS Patients were randomly assigned to receive ixazomib (n 5 425) or placebo (n 5 281). TOURMALINEMM4 met its primary endpoint with a 34.1% reduction in risk of progression or death with ixazomib versus placebo (median PFS since randomization, 17.4 v 9.4 months; hazard ratio [HR], 0.659; 95% CI, 0.542 to 0.801; P,.001; median follow-up, 21.1 months). Ixazomib significantly benefitted patients who achieved complete or very good partial response postinduction (median PFS, 25.6 v 12.9 months; HR, 0.586; P,.001). With ixazomib versus placebo, 36.6% versus 23.2% of patients had grade $ 3 treatment-emergent adverse events (TEAEs); 12.9% versus 8.0% discontinued treatment because of TEAEs. Common any-grade TEAEs included nausea (26.8% v 8.0%), vomiting (24.2% v 4.3%), and diarrhea (23.2% v 12.3%). There was no increase in new primary malignancies (5.2% v 6.2%); rates of on-study deaths were 2.6% versus 2.2%. CONCLUSION Ixazomib maintenance prolongs PFS with no unexpected toxicity in patients with NDMM not undergoing ASCT. To our knowledge, this is the first PI demonstrated in a randomized clinical trial to have single-agent efficacy for maintenance and is the first oral PI option in this patient population. © 2020 by American Society of Clinical Oncology

A staging system was developed a decade ago for patients with Waldenström’s macroglobulinemia (WM), however, since then WM treatments have changed. A revised staging system could better capture prognosis of WM patients in the chemoimmunotherapy era. We developed a revised system based on data from 492 symptomatic patients with at least 3 years and a median of 7 years of follow up while an independent validation cohort included 229 symptomatic patients. We identified age (≤65 vs 66–75 vs ≥76 years), b2-microglobulin ≥ 4 mg/L, serum albumin 65 years and

The exact role of regulatory T cells (Tregs) in multiple myeloma (MM) has not been yet determined. Data regarding alterations of Tregs during therapy with novel agents (NA), i.e., bortezomib and lenalidomide are conflicted and limited. We evaluated prospectively alterations of Tregs and searched for correlations with disease characteristics, response, and outcome in 29 patients with active MM treated with either bortezomib-dexamethasone (BD; 11 patients) or lenalidomide-dexamethasone (LenDex, 18 patients). Additionally, we recorded changes of lymphocytes subsets and cytokines related to Tregs function and MM biology, i.e., interleukin (IL) 6, 2, 17, and TGF-β. Compared with controls, patients had significantly higher median levels of Tregs%, IL-6, and IL-17 (p < 0.001). Median CD4 T and B cells frequencies were significantly lower, whereas CD8 T and natural killers were increased compared to controls. In BD group, no significant alterations of Tregs% were observed. Patients treated with LenDex, displayed a significant reduction of Tregs% (p < 0.001) especially those who achieved at least very good partial response (≥vgPR) (p = 0.04). Lymphocyte subsets or cytokines did not significantly change during therapy. In summary, Tregs% are higher in patients with active MM compared with controls, and they significantly decrease after treatment with LenDex but not with BD; After therapy with LenDex, Tregs reduction between baseline and major response correlated with achievement of ≥vgPR suggesting a possible predictive role, that may contribute to therapeutic strategy. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature.

Aims: Studies have shown that bortezomib retreatment is effective in relapsed/refractory multiple myeloma (MM). The observational, prospective electronic VELCADE® OBservational Study (eVOBS) study assessed bortezomib-based therapies for patients with MM in everyday practice. Here, we report on those patients receiving retreatment with bortezomib. Methods: Consenting adults scheduled to receive bortezomib for MM were enrolled at 162 sites across Europe, Canada, Brazil, Russia, and Turkey between 2006 and 2010. Retrospective data on prior therapies and prospective observational data after bortezomib initiation were captured electronically at baseline, after every bortezomib cycle, and every 12 weeks after discontinuation or progression. Investigator-assessed responses and adverse events (AEs) were evaluated. Results: Ninety-six of 873 patients enrolled to eVOBS received bortezomib as first retreatment for progressive disease during the prospective observation period. Median age was 62 years, 53% were male, and median number of prior therapies at retreatment was 4. Overall, 41% of patients initiated bortezomib retreatment in combination with dexamethasone, 16% in combination with lenalidomide, and 21% received monotherapy. Rate of partial response or better (≥PR) was 75% at initial bortezomib therapy, including 44% complete response (CR)/near CR (nCR); at retreatment, ≥PR rate was 46%, including 15% CR/nCR. Median progression-free survival was 11.4 months (95% confidence interval [CI]: 9.1-12.7) from start of initial bortezomib treatment and 6.4 months (95% CI: 4.4-7.2) from start of retreatment. Median overall survival from start of retreatment was 17.6 months (95% CI: 14.4-23.5). Of the 96 patients retreated with bortezomib, 77% reported an AE. Peripheral neuropathy during bortezomib retreatment occurred in 49% of patients, including 10% grade 3/4. Conclusion: These data suggest that retreatment with bortezomib is a feasible option for patients with relapsed/refractory MM. © 2018 The Authors. Health Science Reports published by Wiley Periodicals, Inc.

There is limited data regarding the efficacy and safety of lenalidomide, adriamycin and dexamethasone (RAD) combination on newly diagnosed multiple myeloma (NDMM) patients. There is also scarce information about the effect of lenalidomide on bone metabolism and angiogenesis in NDMM. Thus, we conducted a Phase 2 study to evaluate the efficacy and safety of RAD regimen as induction in transplant-eligible NDMM patients and we studied the effects on bone metabolism and angiogenesis. A total of 45 patients were enrolled. Following four cycles of RAD, the overall response rate was 66.7% and after a median follow up of 29.1 months (range 21.0–34.9), the median survival outcomes have not been reached yet. RAD had a favorable toxicity profile and did not impair stem cell collection. RAD significantly reduced bone resorption markers CTX (p = 0.03) and TRACP-5b (p < 0.01). Interestingly, RAD also increased bone formation markers bone-specific alkaline phosphatase (p = 0.036), procollagen type 1 amino-terminal propeptide (p = 0.028) and osteocalcin (p = 0.026), which has not been described before with lenalidomide-containing regimens in the absence of bortezomib coadministration. Furthermore, the angiogenic cytokines VEGF (p = 0.01), angiogenin (p = 0.02) and bFGF (p < 0.01) were significantly reduced post-RAD induction. Our results suggest that RAD is an effective induction regimen before autologous stem cell transplantation with beneficial effects on bone metabolism and angiogenesis. © 2019 UICC

The original version of this article contained a mistake. The name of Eirini Katroditou should have been Eirini Katodritou. The original article has been corrected. © 2018, The Author(s).

Objective: The efficacy and safety of bortezomib-based therapy for relapsed/refractory multiple myeloma (RRMM) in clinical trials may differ from the oncology practice experience. The electronic VELCADE® OBservational Study was designed to prospectively evaluate bortezomib for multiple myeloma (MM) in real-world medical practice. Method: Patients scheduled to receive intravenous bortezomib for MM were eligible. The primary objective was to evaluate clinical outcomes, including response, time to response, time to next therapy, treatment-free interval, progression-free survival (PFS), and overall survival (OS). Secondary objectives included safety and healthcare resource utilization. Results: In total, 873 patients with a median of two therapy lines prior to initiating bortezomib were included. The overall response rate (≥partial response) was 69%, including 37% complete response/near-complete response. Median time to response was 1.8 months, median time to next therapy was 9.7 months, and median treatment-free interval was 7.9 months. After 22.6 months’ median follow-up, median PFS was 12.0 months and median OS was 36.1 months. The most common adverse events (AEs) were neuropathy not otherwise specified (19%), diarrhea NOS, and thrombocytopenia (each 17%); 230 (26%) patients discontinued bortezomib due to AEs. Of 689 (79%) patients without baseline peripheral neuropathy (PN), the rate of new-onset any-grade PN increased to 51% (12% grade 3/4) by cycle 8. Overall, 244 (28%) patients were hospitalized, 372 (43%) attended an outpatient visit, and 341 (39%) underwent a diagnostic/therapeutic procedure during bortezomib treatment. Conclusion: These prospective real-world data demonstrate the effectiveness and safety of bortezomib-based therapy for RRMM and confirm high response rates and long OS for this population. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Objective: The efficacy and safety of bortezomib-based therapy for relapsed/refractory multiple myeloma (RRMM) in clinical trials may differ from the oncology practice experience. The electronic VELCADE (R) OBservational Study was designed to prospectively evaluate bortezomib for multiple myeloma (MM) in real-world medical practice. Method: Patients scheduled to receive intravenous bortezomib for MM were eligible. The primary objective was to evaluate clinical outcomes, including response, time to response, time to next therapy, treatment-free interval, progression-free survival (PFS), and overall survival (OS). Secondary objectives included safety and healthcare resource utilization. Results: In total, 873 patients with a median of two therapy lines prior to initiating bortezomib were included. The overall response rate (>= partial response) was 69%, including 37% complete response/near-complete response. Median time to response was 1.8 months, median time to next therapy was 9.7 months, and median treatment-free interval was 7.9 months. After 22.6 months' median follow-up, median PFS was 12.0 months and median OS was 36.1 months. The most common adverse events (AEs) were neuropathy not otherwise specified (19%), diarrhea NOS, and thrombocytopenia (each 17%); 230 (26%) patients discontinued bortezomib due to AEs. Of 689 (79%) patients without baseline peripheral neuropathy (PN), the rate of new-onset any-grade PN increased to 51% (12% grade 3/4) by cycle 8. Overall, 244 (28%) patients were hospitalized, 372 (43%) attended an outpatient visit, and 341 (39%) underwent a diagnostic/therapeutic procedure during bortezomib treatment. Conclusion: These prospective real-world data demonstrate the effectiveness and safety of bortezomib-based therapy for RRMM and confirm high response rates and long OS for this population.

We have studied the efficacy and the prognostic impact of novel agents in 50 primary plasma cell leukemia (pPCL) patients registered in our database. Eighty percent of patients were treated upfront with novel agent-based combinations; 40% underwent autologous stem cell transplantation (ASCT). Objective response rate was 76; 38% achieved at least very good partial response (≥vgPR) and this correlated significantly with bortezomib-based therapy plus ASCT. At the time of evaluation, 40 patients had died. Early mortality rate (≤1 month) was 6%. Median progression-free survival (PFS) and overall survival (OS) were 12 months and 18 months respectively, both significantly longer in patients treated with bortezomib-based therapy + ASCT vs. others (PFS: 18 vs. 9 months; p = 0.004, OS: 48 vs. 14 months; p = 0.007). Bortezomib-based therapy + ASCT predicted for OS in univariate analysis. In multivariate analysis, achievement of ≥vgPR and LDH ≥ 300 U/L were significant predictors for OS. These real-world data, based on one of the largest reported national multicenter series of pPCL patients treated mostly with novel agents support that, among the currently approved induction therapies, bortezomib-based regimens are highly effective and reduce the rate of early mortality whereas in combination with ASCT consolidation they prolong OS. © 2018 The Author(s).