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1708 Primary Mediastinal B Cell Lymphoma (PMBCL): A Multicentric Observational Study of Spanish Lymphoma Group Geltamo

Program: Oral and Poster Abstracts
Session: 626. Aggressive Lymphomas: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Combination therapy, Adult, Clinical Practice (Health Services and Quality), Lymphomas, Non-Hodgkin lymphoma, Drug development, Diseases, Treatment Considerations, Lymphoid Malignancies, Study Population, Human
Saturday, December 7, 2024, 5:30 PM-7:30 PM

Almudena Cabero Martínez1*, Ana García Bacelar2*, Begoña Mendibil Esquisabel, MD3*, Javier Nuñez Cespedes, MD4*, Ana Jiménez Ubieto5*, Eukene Gainza Gonzalez6*, Elena Perez Ceballos7*, Beatriz De La Cruz8*, Ana Garcia Noblejas, MD, PhD9*, Paula Fernández-Caldas10*, Norma C. Gutierrez11*, Blanca Sánchez-González12*, Rocío Figueroa Mora, MD, PhD13*, Alberto Lopez Garcia, MD14, Daniel García Belmonte15*, Maria Sanchez de Castro16*, Estefania Cerezo Velasco, MD17*, Xabier Martin Martitegui18*, Hugo Daniel Luzardo Henríquez19*, Jordina Rovira20*, Luis Antonio Lopez Gomez, MD21*, Jackeline Solano22*, Ana Torres Tienza, PhD23*, Maria Stefania Infante, MD24*, Raquel Santiago Alonso25*, Raquel Del Campo26*, Dunia De Miguel Llorente27*, Alicia Roldán-Pérez28*, Emilia Pardal29*, Beatriz Gonzalez Mena, MD30*, Miguel Ángel Rodríguez Gil31*, Nazaret Domínguez Velasco32*, Albert Blanco Juan33*, Maria Alejandra Blum Dominguez34*, Javier López Marin, MD35*, María Peñarrubia-Ponce36*, Mariana Bastos-Oreiro10* and Alejandro Martín García-Sancho37*

1Hospital Universitario de Salamanca, Instituto de Investigacion Biomedica de Salamanca (IBSAL), Centro de Investigación del Cancer (IBMCC-USAL, CSIC), Salamanca, Spain
2Hematology Department, Hospital Clínico Universitario de valladolid, Valladolid, Spain
3Hospital Universitario de Donostia, Donostia, ESP
4Hospital Universitario Marqués de Valdecilla, Santander, Spain
5Hematology Department, Hospital Universitario 12 de Octubre, Madrid, Spain
6Hematology Department, H.U. GALDAKAO-USANSOLO, Galdakao, Bizkaia, ESP
7Hospotal Morales Meseguer, Murcia, ESP
8Hematology Department, Hospital Universitario La Paz, Madrid, Spain
9Hematology Department, Hospital Universitario La Princesa, Madrid, Spain
10Hematology Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain
11Institute of Biomedical Research of Salamanca (IBSAL), University Hospital, Salamanca, Spain
12Hematology Department, Hospital del Mar, Barcelona, Spain
13Complejo Universitario de Navarra, Navarra, Spain
14Fundacion Jimenez Diaz University Hospital, Madrid, Spain
15Hematology Department, Hospital Universitario La Zarzuela, Madrid, Spain
16Jaen Universitary Hospital, Jaén, Spain
17Hematology Department, Consorcio Sanitario de Terrassa, Terrassa, Spain
18Cruces Universitary Hospital, Bilbao, ESP
19Hematology Department, Hospital Universitario de Gran Canaria Doctor Negrín, Las Palmas de Gran Canaria, Spain
20Hematology Department, Hospital Universitari de Tarragona Joan XXIII, Institut Català d`Oncologia, Tarragona, Spain
21Hematology Department, Hospital Universitario Royo Villanova, Zaragoza, Spain
22Complejo Asistencial de Palencia, Palencia, ESP
23Complejo Asistencial de Segovia, Segovia, ESP
24HOSPITAL INFANTA LEONOR, Madrid, Madrid, ESP
25Hospital Sant Joan de Deu de Manresa, Manresa, Spain
26Hematology Department, Hospital Universitario Son Llàtzer, Palma de Mallorca, ESP
27Hospital Universitario de Guadalajara, Guadalajara, Spain, Guadalajara, Spain
28Hospital Universitario Infanta Sofía, Madrid, Spain
29Hospital Virgen Del Puerto, Plasencia, ESP
30Hospital Universitario Rio Hortega, Valladolid, ESP
31Hospital Universitario Virgen de las Nieves, Granada, Spain
32Hospital Universitario Virgen de la Macarena, Sevilla, Spain
33Hospital Francesc de Borja, Gandia, Spain
34Hospital Recoletas Salud Campo Grande, Valladolid, ESP
35Hospital Universitario Dr.Balmis, Alicante, Spain
36Hospital Clínico Universitario De Valladolid, Valladolid, ESP
37Hematology Department, Hospital Universitario de Salamanca, IBSAL, CIBERONC, University of Salamanca, Salamanca, Spain

Introduction

PMBL accounts for 2-4% of non Hodgkin lymphomas (NHL), predominantly affects young women and presents with a bulky mediastinal mass, often with pleural and pericardial effusions. There is no consensus on upfront treatment for PMBL, although some retrospective studies suggest that more intensive regimens than R-CHOP-21 could improve efficacy results. Thereby, dose adjusted (DA)-EPOCH-R regimen has been adopted as frontline treatment for many centers. Refractory/relapsed (R/R) PMBL has traditionally had a dismal prognosis, but nowadays new therapeutic alternatives are available that could be curative, such as CART therapy.

Methods and objectives

We conducted a retrospective multicenter study within GELTAMO group. Each participating center included patients histologically diagnosed with PMBL from 2007 to 2023. The aim of this study was to analyze clinical and biological characteristics of these patients and the efficacy of frontline and subsequent treatments.

Results

A total of 236 patients from 36 Spanish centers were included. Median age was 35 years (14-69) and there was a female predominance (64%). 65% of patients had bulky mediastinal mass, 39% presented with B symptoms and 69% had high LDH. Most of them had localized disease (stage I-II, 64%), good performance status (ECOG 0-1, 86%), and low risk IPI score (0-1, 62%). Regarding histological findings, the median Ki67 index was 75% (range 15-100%) and most patients were positive for CD30, MUM1, BCL2 and BCL6 (70%, 60%, 62% and 70%, respectively).

All patients received chemoimmunotherapy as first-line, often combined with consolidative radiotherapy (RT). 156 patients (66%) were treated with Da-EPOCH-R, 63 patients (27%) with R-CHOP-21 and 15 patients (6%) received other chemoimmunotherapy regimens. A significantly higher rate of patients treated with R-CHOP-21 versus DA-EPOCH-R received consolidative RT (55.6% vs 21.8%, p<0.01).

The overall response rate (ORR) after first-line was 85.6% (79.2% complete response, CR). Among patients treated with DA-EPOCH-R +/- RT, 83% achieved CR versus 76% of patients treated with R-CHOP-21 +/- RT (p=0.19). In the multivariate analysis, patients with high LDH, B symptoms or superior vena cava syndrome (SVCS) at diagnosis had lower probability of reaching CR.

With a median follow-up in alive patients of 52 months (range 4-214), progression free survival (PFS) and overall survival (OS) at 4 years were 76.8% and 90.5%, respectively. Patients treated with DA-EPOCH-R vs R-CHOP-21 showed a trend toward better PFS (83.1% vs 68.5% at 4 years, p=0.07). In the multivariate analysis, the only factors with independent influence on PFS were high LDH (HR 2.4, 95% CI 1.1 – 5.3, p=0.04) and ECOG≥2 at diagnosis (HR 2.1, 95% CI 1.1–4.1, p=0.03), whereas SVCS (HR 3.6, 95% CI 1.4–9.4, p=0.01) and pleural or pericardial effusion at diagnosis (HR 3.5, 95% CI 1.2-10.4, p=0.03) significantly influence OS.

A total of 52 patients (22%) had R/R disease (54.7% refractory disease) after a median of 7 months (range 1-26), with a higher relapse rate in patients treated with R-CHOP-21 vs DA-EPOCH-R (30.2% vs 18.8%, p=0.05). With a median follow-up of 42 months (range 3-181), PFS2 and OS2 at 36 months were 38% and 70.9%, respectively.

At first relapse, 20 patients (39.2%) received autologous stem cell transplantation (ASCT) as consolidation therapy after second line chemoimmunotherapy. Of them, 16 patients maintain prolonged CR and 4 patients progressed or relapsed after ASCT (3 of them with progression or stable disease before ASCT).

Nine patients received CAR-T cell therapy in third or subsequent treatment lines. Of them, 6 patients achieved CR, 1 PR, 1 patient progressed and 1 patient died early due to CAR-T cell toxicity. All patients who achieved CR maintain that response after a median follow-up of 14 months after CAR-T therapy.

Conclusions

Our results suggest that DA-EPOCH-R could have higher efficacy than R-CHOP-21 with significantly less use of RT. The prognosis is good for most patients, although those with high LDH, ECOG≥2, SVCS or pleural-pericardial effusions had worse survival outcomes. R/R patients seem to have better prognosis than reported in historical series. In this sense, ASCT and CAR-T cell therapy demonstrated very promising results with durable remissions, although these findings should be confirmed in larger series.

Disclosures: Jiménez Ubieto: Janssen: Speakers Bureau; Novartis: Speakers Bureau; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Lilly: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Speakers Bureau; Regeneron Pharmaceuticals, Inc.: Consultancy; Sandoz: Speakers Bureau; Incyte: Speakers Bureau; Kite-Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genmab: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Perez Ceballos: Incyte: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Gutierrez: University Hospital of Salamanca: Current Employment; Amgen, Sanofi: Honoraria. Bastos-Oreiro: Lilly: Honoraria; Sobi: Honoraria; Genmab: Honoraria; Abbvie: Honoraria, Research Funding; Astrazeneca: Honoraria; Gilead: Honoraria, Research Funding; Incyte: Honoraria; Kite: Honoraria, Research Funding; Janssen: Honoraria; Takeda: Honoraria; BMS: Honoraria; Roche: Honoraria, Research Funding. Martín García-Sancho: Miltenyi Biotec: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Lilly: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria; Gilead/Kite: Consultancy, Honoraria, Other: Travel and Accommodation Support; Kyowa Kirin: Consultancy, Honoraria; Genmab: Consultancy, Honoraria; IDEOGEN: Consultancy, Honoraria; Sobi: Consultancy, Honoraria; Takeda: Honoraria; Roche: Honoraria, Other: Travel and Accommodation Support; GSK: Consultancy, Honoraria; Novartis: Consultancy; Janssen: Consultancy, Honoraria, Other: Travel and Accommodation Support; Incyte: Consultancy, Honoraria; EUSA Pharma: Honoraria; Bristol Myers Squibb: Consultancy, Honoraria, Other: Travel and Accommodation Support; BeiGene: Consultancy, Honoraria.

*signifies non-member of ASH