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Background/Aim: Primary mediastinal large B-cell 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 R-CHOP-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.

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.

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.

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 D5PSS5 after consolidative RT should not trigger the initiation of further salvage chemotherapy in the absence of conventionally defined PD.

Background R-CHOP can cure approximately 75% of patients with primary mediastinal large B-cell lymphoma (PMLBCL), but prognostic factors have not been sufficiently evaluated yet. R-da- EPOCH is potentially more effective but also more toxic than R-CHOP. Reliable prognostic classification is needed to guide treatment decisions. Materials and Methods We analyzed the impact of clinical prognostic factors on the outcome of 332 PMLBCL patients ≤65 years treated with R-CHOP ± radiotherapy in a multicenter setting in Greece and Cyprus. Results With a median follow-up of 69 months, 5-year freedom from progression (FFP) was 78% and 5-year lymphoma specific survival (LSS) was 89%. On multivariate analysis, extranodal involvement (E/IV) and lactate dehydrogenase (LDH) ≥2 times upper limit of normal (model A) were significantly associated with FFP; E/IV and bulky disease (model B) were associated with LSS. Both models performed better than the International Prognostic Index (IPI) and the age-adjusted IPI by Harrel's C rank parameter and Akaike information criterion. Both models A and B defined high-risk subgroups (13%–27% of patients [pts]) with approximately 19%–23% lymphoma-related mortality. They also defined subgroups composing approximately one-fourth or one-half of the patients, with 11% risk of failure and only 1% or 4% 5-year lymphoma-related mortality. Conclusion The combination of E/IV with either bulky disease or LDH ≥2 times upper limit of normal defined high-risk but not very-high-risk subgroups. More importantly, their absence defined subgroups comprising approximately one-fourth or one-half of the pts, with 11% risk of failure and minimal lymphoma-related mortality, who may not need more intensive treatment such as R-da-EPOCH. Implications for Practice By analyzing the impact of baseline clinical characteristics on outcomes of a large cohort of patients with primary mediastinal large B-cell lymphoma homogeneously treated with R-CHOP with or without radiotherapy, we developed novel prognostic indices which can aid in deciding which patients can be adequately treated with R-CHOP and do not need more intensive regimens such as R-da-EPOCH. The new indices consist of objectively determined characteristics (extranodal disease or stage IV, bulky disease, and markedly elevated serum lactate dehydrogenase), which are readily available from standard initial staging procedures and offer better discrimination compared with established risk scores (International Prognostic Index [IPI] and age-adjusted IPI).