Real-world data on prognosis and outcome of primary plasma cell leukemia in the era of novel agents: A multicenter national study by the Greek Myeloma Study Group

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)

Real-world data on prognosis and outcome of primary plasma cell leukemia in the era of novel agents: A multicenter national study by the Greek Myeloma Study Group

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)

"real-world" data on the efficacy and safety of lenalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma who were treated according to the standard clinical practice: A study of the Greek Myeloma Study Group

Lenalidomide and dexamethasone (RD) is a standard of care for relapsed/refractory multiple myeloma (RRMM), but there is limited published data on its efficacy and safety in the "real world" (RW), according to the International Society of Pharmacoeconomics and Outcomes Research definition. We studied 212 RRMM patients who received RD in RW. Objective response (≥PR (partial response)) rate was 77.4 % (complete response (CR), 20.2 %). Median time to first and best response was 2 and 5 months, respectively. Median time to CR when RD was given as 2nd or >2nd-line treatment at 4 and 11 months, respectively. Quality of response was independent of previous lines of therapies or previous exposure to thalidomide or bortezomib. Median duration of response was 34.4 months, and it was higher in patients who received RD until progression (not reached versus 19 months, p < 0.001). Improvement of humoral immunity occurred in 60 % of responders (p < 0.001) and in the majority of patients who achieved stable disease. Adverse events were reported in 68.9 % of patients (myelosuppression in 49.4 %) and 12.7 % of patients needed hospitalization. Peripheral neuropathy was observed only in 2.5 % of patients and deep vein thrombosis in 5.7 %. Dose reductions were needed in 31 % of patients and permanent discontinuation in 38.9 %. Median time to treatment discontinuation was 16.8 months. Performance status (PS) and initial lenalidomide dose predicted for treatment discontinuation. Extra-medullary relapses occurred in 3.8 % of patients. Our study confirms that RD is effective and safe in RRMM in the RW; it produces durable responses especially in patients who continue on treatment till progression and improves humoral immunity even in patients with stable disease. © 2013 Springer-Verlag Berlin Heidelberg

Lack of survival improvement with novel anti-myeloma agents for patients with multiple myeloma and central nervous system involvement: the Greek Myeloma Study Group experience

Involvement of the central nervous system (CNS) is a rare complication of multiple myeloma (MM). Herein, we have described the incidence, characteristics, prognostic factors for post CNS-MM survival, and outcome of CNS-MM and explored the efficacy of novel agents (NA) (thalidomide, bortezomib, lenalidomide) in this setting. Between 2000 and 2013, 31 (0.9 %) out of 3408 newly diagnosed symptomatic MM patients, consecutively diagnosed and treated during the same period in 12 Greek centers, developed CNS-MM (M/F 15/16, median age 59 years, range 20–96 years; newly diagnosed/relapsed-refractory 2/29; median time to CNS-MM diagnosis 29 months). Clinical and laboratory characteristics were retrospectively recorded. Twenty-six percent of patients had circulating plasma cells (PCs) or plasma cell leukemia (PCL) at CNS-MM and 39 % had skull-derived plasmacytomas, suggesting hematological and contiguous spread. Treatment for CNS-MM was offered in 29/31 patients and 11/29 responded (NA 18/29, additional radiotherapy 9/28, intrathecal chemotherapy 13/29). The median post CNS-MM survival was 3 months (95 % CI 1.9–4.1) and did not differ between patients treated with NA and/or radiotherapy vs. others. In the multivariate analysis, prior treatment of MM with NA, extramedullary disease (EMD) during MM course (i.e., plasmacytomas, circulating PCs, or documented PCL) and abnormally high LDH at MM diagnosis were independent prognostic factors, whereas treatment of CNS-MM with NA did not predict for post CNS-MM survival. Despite the relatively limited number of patients due to the rarity of CNS-MM, our results suggest that NA do not seem to improve post CNS-MM survival. Patients with EMD display shortened post CNS-MM survival and should be followed thoroughly. © 2015, Springer-Verlag Berlin Heidelberg

Acute lymphoplasmacytoid dendritic cell (DC2) leukemia: Results from the Hellenic Dendritic Cell Leukemia Study Group

We present a cohort of 22 patients with type 2 dendritic cell (DC2) acute leukemia (or blastic plasmacytoid dendritic cell neoplasm-BPDCN, as it has been recently named), diagnosed in Greece over the past 12-year period, according to the main clinical and immunophenotypic features of this entity. Four additional cases are discussed, classified as leukemia of ambiguous lineage (LAL), because of the simultaneous detection of a CD56 negative DC2 population and of a second myeloid precursor cell population. The morphological features and cytogenetic findings of the typical BPDCN cases were similar to those previously described. Acute lymphoblastic leukemia-type chemotherapeutic regimens were more efficient in controlling the disease. Immunophenotyping of typical BPDCN cases revealed CD4+, CD56+, HLA-DR+ and CD123bright neoplastic cells, in the absence of major B-, T- and myeloid-associated markers, while the phenotype of the four cases characterized as LAL highlights the risk of misdiagnosis. Based on our experience, we propose a flow cytometric algorithmic approach for the distinction of typical BPDCN from certain types of acute myeloid leukemia, but also for the identification of acute myeloid leukemia, admixed with CD56 negative DC2 cells, which could be misdiagnosed as BPDCN. © 2009 Elsevier Ltd. All rights reserved

Real-life experience with the combination of polatuzumab vedotin, rituximab, and bendamustine in aggressive B-cell lymphomas

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

Positron emission tomography after response to rituximab-CHOP in primary mediastinal large B-cell lymphoma: impact on outcomes and radiotherapy strategies

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

Positron emission tomography after response to rituximab-CHOP in primary mediastinal large B-cell lymphoma: impact on outcomes and radiotherapy strategies

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