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

Vassilakopoulos, Theodoros P.; Papageorgiou, Sotirios; Angelopoulou, Maria K.; Chatziioannou, Sophia; Prassopoulos, Vassilios; Karakatsanis, Stamatis; Arapaki, Maria; Mellios, Zois; Sachanas, Sotirios; Kalpadakis, Christina; Katodritou, Eirini; Leonidopoulou, Theoni; Kotsianidis, Ιoannis; Hatzimichael, Eleftheria; Kotsopoulou, Maria; Dimou, Maria; Variamis, Eleni; Boutsis, Dimitrios; Terpos, Evangelos; Michali, Evridiki; Karianakis, George; Tsirkinidis, Pantelis; Vadikolia, Chrysanthi; Poziopoulos, Christos; Pigaditou, Anna; Vrakidou, Effimia; Siakantaris, Marina P.; Kyrtsonis, Marie‐Christine; Symeonidis, Argiris; Anargyrou, Konstantinos; Papaioannou, Maria; Chatziharissi, Evdoxia; Vervessou, Elissavet; Tsirogianni, Maria; Palassopoulou, Maria; Gainaru, Gabriella; Mainta, Catherine; Tsirigotis, Panagiotis; Assimakopoulou, Theodora; Konstantinidou, Pavlina; Papadaki, Helen Α.; Dimopoulos, M. A.; Pappa, Vassiliki; Karmiris, Themis; Roussou, Paraskevi; Datseris, Ioannis; Panayiotidis, Panayiotis; Konstantopoulos, Kostas; Pangalis, Gerassimos A.; Rondogianni, Phivi

doi:10.1007/s00277-021-04421-2

Cited by 13 publications

(17 citation statements)

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“…These considerations support the applicability of our risk models in everyday clinical practice. The decision to irradiate or not after induction therapy is currently based on the initial chemotherapy regimen and the final PET result [6,[31][32][33][34][35][36]60,67,68], whereas the impact of baseline prognostic markers on this decision remains to be further delineated. Obviously, the latter issue may not be applicable if patients with one or two risk factors are selected for R-da-EPOCH treatment, where RT is typically omitted.…”

Section: Discussionmentioning

confidence: 99%

Identification of Very Low-Risk Subgroups of Patients with Primary Mediastinal Large B-Cell Lymphoma Treated with R-CHOP

et al. 2021

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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. Rda-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 AE 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

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Section: Discussionmentioning

confidence: 99%

Identification of Very Low-Risk Subgroups of Patients with Primary Mediastinal Large B-Cell Lymphoma Treated with R-CHOP

et al. 2021

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“…7,11,[17][18][19][20][21] Remarkably, using PET-CT as a guide to decide regarding the necessity of RT in PMBCL patients treated with R-CHOP, resulted in a 64% reduction in the number of patients who received consolidative RT, without affecting their outcomes. 6,18,22,23 In the last decade, dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) has become widely accepted as a first-line treatment for PMBCL, allowing to avert the need for RT. A single-center prospective phase II study has reported a 93% event-free survival (EFS) of and 97% OS of at a median follow-up of 63 months following 6-8 cycles of DA-EPOCH-R with no need for subsequent RT in most patients.…”

Section: Introductionmentioning

confidence: 99%

Dose‐adjusted EPOCH‐R is not superior to sequential R‐CHOP/R‐ICE as a frontline treatment for newly diagnosed primary mediastinal B‐cell lymphoma: Results of a bi‐center retrospective study

et al. 2021

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Primary mediastinal B-cell lymphoma (PMBCL) is a rare subtype of diffuse large B-cell lymphoma (DLBCL). Despite its aggressive course, PMBCL is considered curable. While in recent years dose-adjusted (DA) EPOCH-R (rituximab, etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin) has become widely endorsed as first-line therapy for newly-diagnosed PMBCL, the optimal treatment for this disease and the role of radiotherapy (RT) remains unclear. DA-EPOCH-R provides good clinical outcomes, albeit is associated with short-and long-term toxicity. To address this issue, the current retrospective biicenter analysis compared efficacy and toxicity of DA-EPOCH-R and a less toxic R-CHOP/R-ICE regimen used for the treatment of newly-diagnosed PMBCL. Patients and Methods: The study included all patients with a histologically confirmed PMBCL diagnosis treated with DA-EPOCH-R or R-CHOP/R-ICE between 01/2013-12/2020 at two tertiary medical centers. Patient demographic and clinical data were derived from institutional electronic medical records. The analysis included 56 patients: 31 received DA-EPOCH-R and 25 -R-CHOP/R-ICE.Results: At a median follow-up of 1.9 years (IQR 3.1 years), similar progressionfree survival (2.1 versus 2.4 years; p = 0.7667), overall survival (2.5 versus 2.7 years; p = 0.8047) and complete response (80%) were observed in both groups.However, DA-EPOCH-R was associated with significantly longer hospitalization required for its administration (p < 0.001) and a trend for higher frequency of infections, stomatitis, thrombotic complications and febrile neutropenia-related hospitalizations. Conclusion: DA-EPOCH-R and R-CHOP/R-ICE provide similarly encouraging outcomes in newly-diagnosed PMBCL patients. R-CHOP/R-ICE is associated with lower toxicity and significantly reduced hospitalization. Our findings How to cite this article: Morgenstern Y, Aumann S, Goldschmidt N, Gatt ME, Nachmias B, Horowitz NA. Dose-adjusted EPOCH-R is not superior to sequential R-CHOP/R-ICE as a frontline treatment for newly diagnosed primary mediastinal B-cell lymphoma: Results of a bi-center retrospective study.

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“…The authors reported a 5-year freedom from progression of 92% versus 44% for patients with DS4 and DS5, respectively. 28 Similarly, the British Columbia group reported 5-year time to progression of 57% in the DS5 group after R-CHOP induction. 15 These results corroborate the need for novel approaches in patients with DS5 on EOT-PET.…”

Section: Treatment Strategies In the Frontline Settingmentioning

confidence: 95%

Current and emerging treatment options in primary mediastinal B-cell lymphoma

Fakhri

2021

Therapeutic Advances in Hematology

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Previously considered a subtype of diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL) is now recognized by the World Health Organization as an independent entity. PMBCL has clinicopathologic features that are separate from systemic DLBCL and harbors some biologic characteristics which overlap with nodular sclerosing classic Hodgkin’s lymphoma (cHL). Similar to cHL, copy number alterations of 9p24.1 are frequently seen in PMBCL, which leads to increased expression of key genes in the region, including programmed death-ligand 1( PD-L1), PD-L2, and JAK2. In addition, PMBCL cells express CD30 in a mostly patchy fashion. In the upfront setting, dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (i.e., DA-EPOCH-R) is the only regimen that has been shown in a prospective setting to result in outstanding outcomes without consolidative radiation to the mediastinum, with a 5-year event-free survival rate of 93% and overall survival rate of 97%. Thus, in recent years, DA-EPOCH-R has been recognized as the preferred frontline regimen. Despite the encouraging results in the frontline setting, the outcomes in the relapsed/refractory setting remain poor. The current approach of salvage chemotherapy followed by autologous stem cell transplantation, as used in patients with DLBCL, does not result in high rates of cure in patients with rrPMBCL. In recent years, the characteristic molecular features identified in PMBCL have provided more treatment opportunities for this patient population. In the relapsed setting, single-agent PD-1 inhibitor pembrolizumab have demonstrated high and durable remission rates. Despite the expression of CD30, the CD30 antibody drug-conjugate brentuximab vedotin (BV) as a single agent has been deemed inactive in this disease. On the contrary, the combinations of BV and PD-1 inhibitor have shown higher response rates than PD-1 inhibitor alone. Moreover, anti-CD19 chimeric antigen receptor T-cell (CAR T-cell) therapy has been positioned as another successful strategy for patients with rrPMBCL. Axicabtagene ciloleucel and lisocabtagene maraleucel are two products used in rrPMBCL.

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

Cited by 13 publications

References 38 publications

Identification of Very Low-Risk Subgroups of Patients with Primary Mediastinal Large B-Cell Lymphoma Treated with R-CHOP

Identification of Very Low-Risk Subgroups of Patients with Primary Mediastinal Large B-Cell Lymphoma Treated with R-CHOP

Dose‐adjusted EPOCH‐R is not superior to sequential R‐CHOP/R‐ICE as a frontline treatment for newly diagnosed primary mediastinal B‐cell lymphoma: Results of a bi‐center retrospective study

Current and emerging treatment options in primary mediastinal B-cell lymphoma

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