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4403 Evolution of Treatment Patterns and Sequencing in Mantle Cell Lymphoma (MCL) in Spain and Their Impact on Survival. the Geltamo-MCL-2022 Study

Program: Oral and Poster Abstracts
Session: 623. Mantle Cell, Follicular, Waldenstrom’s, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Poster III
Hematology Disease Topics & Pathways:
Combination therapy, Adult, Clinical Practice (Health Services and Quality), Therapy sequence, Treatment Considerations, Study Population, Human
Monday, December 9, 2024, 6:00 PM-8:00 PM

Ana Marin Niebla, MD PhD1*, Mariana Bastos-Oreiro2*, Amanda Isabel Perez, MD3*, Alba Cabirta Touzón, MD4*, Fatima De la Cruz Vicente, MD5*, Marta Canelo6*, Ana Jiménez Ubieto7*, Sonia González De Villambrosia8*, Ana Muntañola9*, Hugo Daniel Luzardo Henríquez10*, Eduardo Rios Herranz, MD11*, Pilar Gómez12*, Alberto López, MD13*, Ana Saus Carreres14*, Alejandro Martín García-Sancho15*, Ana Garcia Noblejas16*, Carlos Grande17*, Pablo Prieto Martinez, MD18*, Concepción Nicolás19*, Antonio Gutierrez, MD, PhD20*, Jose-Angel Hernandez Rivas, MD, PhD21*, Blanca Sánchez González22*, Rosalia Alonso Trillo, MD23*, Eva Donato24*, Paola Villafuerte Gutiérrez25*, Daniel García Belmonte26*, Silvia Rocio Verdesoto Cozzarelli27*, Sandra Suarez Ordoñez, MD28*, Emilia Pardal De La Mano29*, Lucia Villalon Blanco30*, Alicia Roldán-Pérez31*, Eva Gine, MD32, Juan-Manuel Sancho, MD, PhD33*, Raul Cordoba, MD, PhD34, Beatriz De La Cruz35*, Victor Navarro Garces, BSc36* and Pau Abrisqueta, MD PhD37

1Hematology Department, Vall d’Hebron Institute of Oncology (VHIO), University Hospital Vall d’Hebron, Barcelona, Spain
2Hematology Department, General University Hospital Gregorio Marañón, Madrid, Spain
3Hematology Department, Hospital Clinic de Barcelona, ICMHO, Barcelona, Spain
4Hematology Department, Vall d'Hebron Institute of Oncology (VHIO), University Hospital Vall d'Hebron, Barcelona, Spain
5Instituto de Biomedicina de Sevilla (IBIS)/CSIC/Universidad de Sevilla, University Hospital Virgen del Rocío, Seville, Spain
6Hematology Department, Hospital Universitario Germans Trias i Pujol, Badalona, Barcelona, Spain
7Hematology Department, Hospital Universitario 12 de Octubre, Madrid, Spain
8Hematology Department, Hospital Universitario Marqués de Valdecilla (IDIVAL), Santander, Spain
9Hematology Department, Hospital Santa Creu i Sant Pau, Barcelona, Spain
10Hematology Department, Hospital Universitario de Gran Canaria Doctor Negrín, Las Palmas de Gran Canaria, Spain
11Hematology Department, University Hospital Ntra. Sra de Valme, Seville, Spain
12Hospital La Paz, Madrid, Spain
13Hematology Department, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain
14Hematology Department, Hospital Clínico de Valencia, Valencia, Spain
15Hospital Universitario de Salamanca, IBSAL, CIBERONC, Universidad de Salamanca, Salamanca, Spain
16Hospital Universitario la Princesa, Madrid, ESP
17Hematology Department, Clínica Universidad de Navarra, Madrid, Spain
18Hematology Department, Hospital Universitario Puerta de Hierro, Madrid, Spain
19Hematology Department, Hospital Universitario Central de Asturias, Oviedo, Spain
20Hematology Department, Hospital Universitario Son Espases, IdISBa, Palma de Mallorca, Spain
21Hospital Universitario Infanta Leonor, Universidad Complutense, Madrid, Spain
22Hematology Department, Hospital del Mar, Barcelona, Spain
23Hematology Department, Hospital Universitario de Getafe, Madrid, Spain
24Hematology Department, Hospital Universitario Doctor Peset, Valencia, Spain
25Hematology Department, Hospital Universitario Principe de Asturias, Madrid, Spain
26Hematology Department, Hospital Universitario La Zarzuela, Madrid, Spain
27Hematololgy Department, Hospital de San Juan Despí Moisès Broggi, Barcelona, ESP
28Hematology Department, Complejo Hospitalario de Vigo, Vigo, Spain
29Hematology Department, Hospital Virgen del Puerto, Plasencia, Cáceres, Spain
30Hospital Universitario Fundación Alcorcón, Alcorc N, Madrid, ESP
31Hematology Department, Hospital Universitario Infanta Sofía, Madrid, Spain
32Department of Hematology, ICAMS, Hospital Clínic de Barcelona, Barcelona, Spain
33ICO-IJC-Hospital Germans Trias i Pujol, Barcelona, Spain
34Hematology, University Hospital Fundación Jiménez Díaz, Madrid, Spain
35Hematology Department, Hospital Universitario La Paz, Madrid, Spain
36Statistics Unit, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain
37Department of Hematology, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron University Hospital, Barcelona, Spain

INTRODUCTION:

MCL remains incurable and its management widely heterogeneous in clinical practice. We analyzed how the patterns and sequencing of treatments have evolved in Spain over the years and their impact on the survival of patients with MCL.

PATIENTS AND METHODS:

We retrospectively analyzed the management, efficacy data and progression-free and overall survival (PFS and OS) of patients with MCL included in the GELTAMO-MCL-2022 study. First-line (1L) treatments were grouped as HiDAC (containing HD-AraC) or non-HiDAC, second-line (2L) as BTKi (BTK inhibitors in monotherapy or combinations), ICT (standard salvage immunochemotherapy) or others (regimens with other targeted agents). We considered early relapse/progression (E-POD) when occurred within 24 months (m) from diagnosis and late (L-POD) beyond 24 m, including patients dying from MCL before 24 months as E-POD and patients still in response after 1L ≥24m at data cut-off as L-POD. Kaplan-Meier was used to analyze survival and the COX model for HR (CI95%) and p value of factors associated with PFS and OS.

RESULTS:

This study included 1105 patients with MCL diagnosed from 2000-2023 in 32 GELTAMO centers. Clinical-biologic and demographic characteristics are comparable with other reported real-world cohorts. At data cut-off (july 2024), 553 patients (50%) had died, being the lymphoma the main cause of death (n= 295, 53%). Out of 1051 patients treated in 1L, 112 (10.6%) received treatment after a median (M) time in “watch and wait” of 19 m (2-156) and 939 (89%) immediately after diagnosis, with a M number of 1 treatment line (0-10) for the entire cohort. After 1L, 49% (N=515) had not received further lines: 331 were in ongoing response but 35.8% were lost before 2L (18 lost of follow-up and 166 exitus).

In patients treated at diagnosis (excluding indolent cases receiving 1L after observation), 1L with HiDAC had higher Overall and Complete Responses (OR, CR) (88% vs. 78%, p=.002 and 77% vs. 61%, p<.001) while Non-HiDAC showed higher rates of E-POD (68% vs. 47%, p<.001). In 53 patients receiving BTKis in 1L (2 monotherapy and 51 with rituximab or ICT), ORR was 92.4% and CR 85% (significantly higher than HiDAC, p=.02). In Spain, 1L regimens are mainly R-CHOP-based (93% of HiDAC and 56% of nonHiDAC) but the pattern shifted over the years, R-Bendamustine becoming the preferred option for older patients from 2016. Out of 757 achieving CR/PR after 1L, 277 patients (35.6%) underwent autologous transplant (ASCT) in 1L (79% after HiDAC) and 368 rituximab maintenance (RM): after ASCT in 111 (30%) and after induction in 216 (81% nonHiDAC). RM and ASCT were associated with longer PFS and OS (HR=0.34, (0.28, 0.42) and HR=0.39 (0.29, 0.52) for RM and HR=0.35 (0.27, 0.46) and HR=0.45 (0.30, 0.68) for ASCT).

In 405 evaluable patients for 2L from 2013 (first BTKi recorded in our database), 197 received BTKi, 183 ICT and 25 other targeted-based treatments. BTKi and ICT showed comparable efficacy (ORR 61%/65% p=.5 and CR 39%/47% p=.07) and impact on OS-2 (HR=0.98, p=.097). From its launch in Spain in 2016, ibrutinib progressively replaced ICT, becoming the first choice in 2L. Only 25.6% of patients treated in 1L received ≥3 lines, predominating targeted agents other than BTKis in the subsequent lines.

With M FU=90.2m (84.3-99.3), M OS is 6.8 years and M PFS 39m, PFS progressively decreasing with each subsequent treatment line. MR, ASCT and BTKi used in 1L were the only treatment-related factors associated with longer PFS and OS in the MVAs.

CONCLUSIONS:

  1. HiDAC regimens are associated with higher efficacy and late relapses vs. non-HiDAC in our cohort, although without impact on PFS or OS (in MVA). Both ASCT and RM after 1L are associated with longer PFS and OS but, while 79% of patients eligible for intensive treatment receive ASCT 1L, only 45% of eligible patients receive RM.
  2. In our patients, BTKis in 2L show efficacy and survival rates similar to ICT and, with a more convenient oral administration and manageable toxicity profile, has become the choice at first relapse in Spain from 2016.
  3. After 1L, PFS remains progressively shorter with each subsequent line and we lose up to 34.5% of patients before 2L, which highlights the need of using the most effective agents as soon as possible from the 1L, since patients with MCL might miss their only chance to improve survival.

Disclosures: Marin Niebla: Eli Lilly: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria; Abbvie: Consultancy; Johnson&Johnson: Consultancy, Honoraria. De la Cruz Vicente: Abbvie, Beigene, Iowa, Eusa Pharma, Janssen, Roche, Takeda: Consultancy, Honoraria. Jiménez Ubieto: Janssen: Speakers Bureau; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Speakers Bureau; Regeneron Pharmaceuticals, Inc.: Consultancy; Lilly: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sandoz: Speakers Bureau; Novartis: 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. Martín García-Sancho: Lilly: Consultancy, Honoraria; Miltenyi Biotec: Consultancy, Honoraria; Gilead/Kite: Consultancy, Honoraria, Other: Travel and Accommodation Support; Kyowa Kirin: Consultancy, Honoraria; IDEOGEN: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Novartis: Consultancy; GSK: Consultancy, Honoraria; Genmab: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Takeda: Honoraria; Sobi: Consultancy, Honoraria; Roche: Honoraria, Other: Travel and Accommodation Support; Janssen: Consultancy, Honoraria, Other: Travel and Accommodation Support; EUSA Pharma: Honoraria; Bristol Myers Squibb: Consultancy, Honoraria, Other: Travel and Accommodation Support; BeiGene: Consultancy, Honoraria. Hernandez Rivas: Janssen, Roche, Abbvie, AstraZeneca, Beigene, Lilly, Gilead, BMS-Celgene, Amgen, Takeda, Jazz Pharmaceuticals, Rovi, Incyte, MSD: Membership on an entity's Board of Directors or advisory committees; Janssen, Roche, Abbvie, AstraZeneca, Gilead, BMS-Celgene, Amgen, Takeda, Astra Zeneca, Lilly, Beigene: Other: Scientific Talks; BMS-Celgene: Research Funding. Gine: Lilly: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Roche: Honoraria; Gilead/Kite: Honoraria; Astra-Zeneca: Honoraria. Sancho: Novartis: Membership on an entity's Board of Directors or advisory committees; Beigene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb-Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Sobi: Membership on an entity's Board of Directors or advisory committees; Lilly: Honoraria, Membership on an entity's Board of Directors or advisory committees; Myltenyi Biomedicine: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead-Kite: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Abrisqueta: Roche: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; Abbvie: Consultancy, Honoraria, Speakers Bureau; Astrazeneca: Consultancy, Honoraria, Speakers Bureau; Beigene: Consultancy; Janssen: Consultancy, Honoraria, Speakers Bureau; Incyte: Honoraria, Speakers Bureau.

*signifies non-member of ASH