Summary The incidence, characteristics and risk factors for the development of osteonecrosis of the jaw (ONJ) were evaluated among 303 myeloma patients. Only patients who received bisphosphonates developed ONJ (28/254; 11%). Zoledronic acid produced 9·5‐fold greater risk for developing ONJ than pamidronate alone (P = 0·042) and 4·5‐fold greater risk than subsequent use of pamidronate + zoledronic acid (P = 0·018). Use of thalidomide and number of bisphosphonate infusions also increased the risk for ONJ by 2·4‐fold (P = 0·043), and 4·9‐fold respectively (P = 0·012). ONJ developed earlier among patients receiving zoledronic acid. Our data indicates that administration of zoledronic acid for more than 2 years or in combination with thalidomide requires caution in myeloma.

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.

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The aim of the study was to evaluate the role of hypochromic erythrocytes (HYPO%) compared to "traditional" and novel markers of iron status and erythropoiesis in recognizing iron-restricted erythropoiesis (IRE) and predicting response to erythropoietin (rHuEPO) in anemic patients with myeloma and lymphoma. Forty-one newly diagnosed patients who received epoetin-beta at a subcutaneous weekly dose of 30,000 IU for 6 weeks were studied. Response to rHuEPO was observed in 27 patients (65.8%). Twelve non-responders received, additionally, 200 mg of IV iron sucrose, weekly, for 4 weeks. Evaluation of markers was performed at baseline and on weeks 1, 2 and 6 for all patients and also on weeks 7-10 for non-responders to rHuEPO. Baseline HYPO%, at a cut-off value of <5%, and an increment in reticulocyte absolute number (RETICS-AB) >or= 50,000/microl and reticulocyte hematocrit (RETICS-Hct) >or= 50%, between baseline and week 2, were independent predictive factors for response to rHuEPO. We found that these markers had superior predictive value for response to rHuEPO than four widely used predictive models. Furthermore, a baseline HYPO% count of above 5% proved superior over serum ferritin < 100 ng/ml and transferrin saturation < 20% in recognizing IRE. In conclusion, baseline HYPO% either alone or in combination with RETICS-AB or RETICS-Hct after 2 weeks of rHuEPO treatment could be reliably used in predicting response to rHuEPO. Additionally, HYPO% has proved a reliable marker for recognizing IRE before rHuEPO treatment and, thus, could be used for identifying patients who will benefit from IV iron supplementation.

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TACI is a membrane receptor of BAFF and APRIL, contributing to the differentiation and survival of normal B cells. Although malignant B cells are also subjected on TACI signaling, there is a remarkable intradisease and interindividual variability of TACI expression in B-cell malignancies. The aim of our study was to explore the possible role of TACI signaling in the biology of chronic lymphocytic leukemia (CLL), including its phenotypic and clinical characteristics and prognosis. Ninety-four patients and 19 healthy controls were studied. CLL patients exhibited variable TACI expression, with the majority of cases displaying low to undetectable TACI, along with low to undetectable BAFF and increased APRIL serum levels compared to healthy controls. CLL cells with high TACI expression displayed a better survival capacity in vitro, when cultured with BAFF and/or APRIL. Moreover, TACI expression was positively correlated with the presence of monoclonal gammopathy and inversely with CD11c expression. Therefore, our study provides further evidence for the contribution of BAFF/APRIL signaling to CLL biology, suggesting also that TACI detection might be useful in the selection of patients for novel targeting therapeutic approaches.

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Renal impairment is a common complication of multiple myeloma (MM). Standard assessment of kidney function in MM includes serum creatinine and creatinine clearance (Ccr) that possibly underestimate the prevalence of renal impairment in this disease. Cystatin-C (Cys-C) is a cysteine-proteinase inhibitor, which participates in the intracellular protein catabolism. It is freely filtered in the glomeruli and totally reabsorbed in the proximal tubular cells; therefore, it is a perfect endogenous marker of glomerular filtration rate. The aim of this study was to evaluate the serum levels of Cys-C in MM and explore possible correlations with clinical data, including survival. We studied 157 newly-diagnosed MM patients (87M/70F, median age 68 years), 28 patients with relapsed disease (17M/11F, median age 68 years) pre- and post-bortezomib therapy, and 15 healthy controls (9M/6F, median age 67 years). Serum Cys-C was determined by particle enhanced immunonephelometry (Dade Behring, Liederbach, Germany). In newly-diagnosed MM patients, serum Cys-C was increased compared with controls [median (range) 1.01 mg/L (0.24–5.61 mg/L) vs. 0.7 mg/L (0.59–0.95 mg/L); p&lt;0.0001]. Ninety patients (57.3%) had higher Cys-C levels than the upper normal limit of 0.95 mg/L, while only 35 (22.2%) had elevated serum creatinine. Patients with ISS stage 3 had increased median Cys-C (1.91 mg/L) compared with stage 1 (0.84 mg/L; p&lt;0.0001) and stage 2 patients (0.95 mg/L; p&lt;0.0001). Cys-C showed strong correlations with beta2-microglobulin (r=0.648, p&lt;0.0001), creatinine (r=0.705, p&lt;0.0001), Ccr (r=−0.549, p&lt;0.0001) and urea (r=0.471, p&lt;0.0001), and weaker correlations with albumin (r=−0.241, p=0.002), hemoglobin (r=−0.333, p&lt;0.0001), LDH (r=0.177, p=0.027) and ferritin (r=0.277, p=0.001). The median survival of all patients was 48 months and the median follow-up period was 26 months. The univariate analysis showed that Cys-C, beta2-microglobulin, LDH, hemoglobin, Ccr, and ISS stage predicted for survival. The median survival for patients with normal Cys-C levels (≤0.95 mg/L) has not been reached yet, while in patients with high Cys-C (&gt;0.95 mg/L) the median survival was 27 months (95% CI 16.9–37.0; p&lt;0.0001). The multivariate analysis revealed that only Cys-C and LDH had independent prognostic value. Patients with both high levels of Cys-C and LDH (&gt;upper normal limit) (n=46) had a median survival of 24 months (95% CI 18.2–29.7), while the median survival of all other patients has not been reached yet (p&lt;0.0001). Cys-C could also separate patients with ISS 2 in terms of survival: patients with elevated Cys-C (n=25) had a median survival of 37 months, while the median survival of patients with normal Cys-C levels (n=26) has not been reached yet (p=0.021). Patients with relapsed myeloma had increased median Cys-C (1.36 mg/L) compared with controls (p&lt;0.0001) and newly-diagnosed patients (p&lt;0.01). Bortezomib therapy produced a strong reduction of Cys-C levels (median: 1.07 mg/L, p&lt;0.01). Responders had a greater reduction than non-responders (p&lt;0.01). The results of this study suggest that Cys-C is a sensitive marker of renal impairment and predicts independently for survival in MM. Furthermore, Cys-C seems to be able to separate ISS 2 patients in terms of survival. Bortezomib monotherapy reduces Cys-C levels, mainly in responders.