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Patients relapsing early after autologous stem cell transplantation (ASCT) are a particular therapeutic challenge.This was a retrospective, single center study that included 297 consecutive patients that received first-line ASCT RESULTS: We identified 43 (14.5%) patients that relapsed within12 months. At diagnosis, these patients had more often elevated lactate dehydrogenase, lower estimated glomerular filtration rate, hypercalcemia, and high-risk cytogenetics; the International Staging System stage distribution was similar. Consolidation and maintenance were associated with lower rates of early relapses. Progression-free survival to second-line therapy was 5 months versus 19 months for those with an early versus late relapse (P .001), the median PFS to second-line therapy was 15.5 months versus5 years (P .001) and the median post-ASCT survival was 18 months versus6 years. The survival after an early relapse has not improved significantly over time. In multivariate analysis, early relapse (hazard ratio, 14; P .001) was the most important prognostic factor for poor survival after ASCT.Patients relapsing12 months after ASCT comprise an ultra-high-risk group, with poor outcomes even with the application of the more recent combinations, that urgently needs more effective therapies.

In patients with myelodysplastic syndrome (MDS), the prognostic significance of chromosome 17 abnormalities has not yet been fully elucidated, except for isochromosome 17q that has been characterized as an intermediate risk abnormality in the Revised International Prognostic Scoring System (IPSS‐R). To further characterize the prognostic significance of chromosome 17 abnormalities we analyzed the hematologic and prognostic characteristics of 548 adult patients with MDS treated with 5‐azacytidine through the Hellenic 5‐azacytidine registry and found 32 patients with a chromosome 17 abnormality (6 with i[17q], 15 with ‐17, 3 with add[17p] and the rest with other rarer abnormalities, mostly translocations). The presence of a chromosome 17 abnormality was correlated with poor prognostic features (high IPSS, IPSS‐R, and WPSS scores) and a low overall survival rate (15.7 vs 36.4 months for patients without chromosome 17 abnormalities, Kaplan–Meier, Log Rank P

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.

The demethylating factor 5-azacytidine (5-AZA) improves survival in intermediate-2 and high-risk myelodysplastic syndrome (MDS) patients [according to the International Prognostic Score System (IPSS)] responding to treatment. However, the outcome of patients achieving stable disease (SD) is unclear. This retrospective study of the Hellenic MDS Study Group included 353 intermediate-2 or high IPSS risk patients treated with 5-AZA. Forty-four out of 86 (51.6%) patients achieving SD and continuing treatment with 5-AZA showed a lower risk of transformation of MDS to acute myeloid leukemia (AML) and increased overall survival (OS), compared to SD patients who discontinued the treatment (estimated median AML-free survival = 38 months, 95% CI = 10.7-65.3 vs 15 months, 95% CI = 10.4-19.6, P < .001; estimated median OS = 20 months, 95% CI = 5.5-34.5 vs 11 months, 95% CI = 5.8-16.2, P < .001). Moreover, SD patients continuing treatment with 5-AZA had no differences in AML-free survival compared to patients showing response to 5-AZA (estimated median AML-free survival = 38 months, 95% CI = 10.7-65.3 vs 31 months, 95% CI = 23.6-38.4, P = .45; estimated median OS 20 months, 95% CI = 5.5-34.5 vs 25 months, 95% CI = 21.3-28.7, P = .50). In conclusion, MDS patients achieving SD in the first 6 months of treatment with 5-AZA as best response should continue receiving 5-AZA as they may benefit from prolonged treatment.

In this study, we investigated the incidence and prognostic impact of monosomal karyotype (MK) in 405 higher-risk Myelodysplastic Syndromes (MDS) patients treated with 5-AZA. The MK was present in 66 out of 405 (16.3%) patients, most of whom had complex karyotype (CK). MK was strongly associated with CK and the cytogenetic risk defined according to IPSS-R, as well as with high-risk disease, according to IPSS (P = .029), IPSS-R (P < .001), and WPSS (P < .001) classification systems. The overall response rate (ORR) was not different between MK+ and MK- patients (46.6% vs. 46.2%). At 28 months median follow-up, the median duration of response was 11 months in the entire cohort, 9.5 months in MK+ patients and 11 months in MK-patients (P = .024). The estimated median time to transformation to acute myeloid leukemia for MK+ patients was 17 months vs. 23 months for MK- patients (P = .025). The estimated median OS for MK+ patients was 12 months vs. 18 months for MK- patients (P < .001). Multivariate Cox regression analysis revealed that performance status (P < .001), IPSS-R (P < .001), and MK (P = .002) were independently associated with overall survival (OS). In a subgroup consisting of high and very-high risk patients according to IPSS-R, MK- patients showed better OS rates compared to MK+ patients (estimated median OS: 17 months vs. 12 months, P = .002). In conclusion, we found that MK is associated with reduced OS in patients with higher-risk MDS treated with 5-AZA. Furthermore, we showed that in MDS with high or very-high IPSS-R risk score, MK can further distinguish patients with worse outcome.

Myeloma cells thrive in an environment of sustained inflammation, which impacts the development and evolution of the disease, as well as drug resistance. We evaluated the impact of genetic polymorphisms in the Toll-like receptor 4 (TLR4) pathway, which have been implicated in different inflammatory responses in the outcomes of patients with symptomatic multiple myeloma (MM) who have received contemporary therapies. We found that the presence of single nucleotide polymorphisms (SNPs) in both the TLR4 and toll/interleukin-1 receptor (TIR)-associated protein (TIRAP) genes was associated with lower response to primary therapy mainly for patients who received immunomodulatory drugs but not in patients treated with bortezomib-based therapies. Furthermore, TIRAP SNP was associated with a significantly shorter progression-free survival and overall survival, independently of other prognostic factors, such as age, transplant, International Staging System stage, lactate dehydrogenase and cytogenetics. This is the first study to demonstrate the effect of SNPs in TLR4/TIRAP in MM. Our data indicate that genetic variability in the immune system may be associated with different responses to antimyeloma therapies and may be a critical component affecting the natural history of the disease, providing the basis for further investigation of the role of these pathways in myeloma.

Renal failure (RF) is a common and severe complication of symptomatic myeloma, associated with significant morbidity and mortality. Such patients are commonly excluded from clinical trials. Bortezomib/dexamethasone (VD)-based regimens are the backbone of the treatment of newly diagnosed MM patients who present with severe RF even those requiring dialysis. We analyzed the outcomes of 83 consecutive bortezomib-treated patients with severe RF (eGFR 30 ml/min/1.73 m(2) ), of which 31 (37%) required dialysis. By IMWG renal response criteria, 54 (65%) patients achieved at least MRrenal, including CRrenal in 35% and PRrenal in 12%. Triplet combinations (i.e., VD plus a third agent) versus VD alone were associated with higher rates of renal responses (72 vs. 50%; P = 0.06). Fifteen of the 31 (48%) patients became dialysis independent within a median of 217 days (range 11-724). Triplets were associated with a higher probability of dialysis discontinuation (57 vs. 35%). Serum free light chain (sFLC) level ≥11,550 mg/L was associated with lower rates of major renal response, longer time to major renal response, lower probability, and longer time to dialysis discontinuation. Rapid myeloma response (≥PR within the first month) was also associated with higher rates of renal response. Patients who became dialysis-independent had longer survival than those remaining on dialysis. In conclusion, VD-based triplets are associated with a significant probability of renal response and dialysis discontinuation, improving the survival of patients who became dialysis independent. Rapid disease response is important for renal recovery and sFLCs are predictive of the probability and of the time required for renal response.