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3205 Assessment of the IPSS-M in Chronic Myelomonocytic Leukemia

Program: Oral and Poster Abstracts
Session: 637. Myelodysplastic Syndromes: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
Research, Health outcomes research, Clinical Research, Diseases, Registries, Myeloid Malignancies
Sunday, December 8, 2024, 6:00 PM-8:00 PM

Laura Palomo, PhD1*, Mireia Morgades2*, Manja Meggendorfer, PhD3, Marina Díaz-Beyá, MD, PhD4*, Helena Pomares5*, Guillermo Ramil López, MD6*, Mariam Ibañez7*, Mar Tormo, MD8, Felix Lopez, MD9*, Alejandro Avendaño Pita10*, Juan Carlos Caballero11*, Jordi Vila Bou12*, Juan Restrepo13*, Veronica Roldan14*, Pilar Galán15*, Estefania Cerezo Velasco, MD16*, Cristina Notario17*, ANA Garcia Feria18*, Torsten Haferlach, MD19, Sandra Castaño-Díez, MD4*, Esther Alonso20*, Marta Pratcorona, MD, PhD6*, Rosa Collado21*, Marisa Calabuig22*, Pamela Acha23*, Gerardo Aguilar-Monserrate11*, Marta Cabezón2*, Neus Ruiz Xiville, PhD2*, Maria Diez-Campelo, MD, PhD24*, Lurdes Zamora, PhD25* and Blanca Xicoy, MD26*

1ICO-Hospital Germans Trias i Pujol, Institut de Recerca contra la Leucèmia Josep Carreras (IJC), Universitat Autònoma de Barcelona, Badalona, ESP
2ICO-Hospital Germans Trias i Pujol, Institut de Recerca contra la Leucèmia Josep Carreras (IJC), Universitat Autònoma de Barcelona, Badalona, Spain
3MLL Munich Leukemia Laboratory, Munich, Bavaria, Germany
4Hematology Department, Hospital Clínic de Barcelona, Barcelona, Spain
5Clinical Hematology Department, ICO-Hospitalet, Hospital Durán i Reynals. IDIBELL, Barcelona., Barcelona, Spain
6Hematology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
7Hospital General Universitario de Valencia, Valencia, ESP
8Department of Hematology and Medical Oncology,, Hospital Clínico Universitario de Valencia. INCLIVA Biomedical Research Institute, Valencia, Spain
9Experimental Hematology, Hospital Universitario Vall d’Hebrón, Institut d’Oncologia Vall d’Hebrón (VHIO), Barcelona, ESP
10Hospital Universitario de Salamanca, Instituto de Investigacion Biomedica de Salamanca (IBSAL), Centro de Investigación del Cancer (IBMCC-USAL, CSIC), Salamanca, Spain
11Hospital Clínico Universitario de Valladolid, Valladolid, Spain
12Institut Català d’Oncologia - Hospital Universitari de Girona Dr. Josep Trueta, Girona, ESP
13Institut Català d’Oncologia - Hospital Universitari de Tarragona Joan XXIII, Tarragona, Spain
14Hospital Universitario Cruces, Bilbao, Spain
15Complejo Asistencial de Segovia, Segovia, ESP
16Hematology Department, Consorcio Sanitario de Terrassa, Terrassa, Spain
17Hospital Universitario Nuestra Señora de la Candelaria, Santa Cruz de Tenerife, Spain
18Hospital Universitario Doctor Peset, Valencia, Spain
19MLL Munich Leukemia Laboratory, Munich, Germany
20Hospital De Bellvitge, L'Hospitalet De Llobregat, Ba, ESP
21Hospital Clínico Universitario de Valencia, Instituto de Investigación Sanitaria INCLIVA, Valencia, ESP
22Hospital Clínico Universitario de Valencia, Valencia, Spain
23Experimental Hematology, Hospital Universitario Vall d’Hebrón, Institut d’Oncologia Vall d’Hebrón (VHIO), Barcelona, Spain
24Hospital Clínico Universitario de Salamanca, Salamanca, Spain
25Haematology Department, ICO-Hospital Germans Trias i Pujol, Institut de Recerca contra la Leucèmia Josep Carreras (IJC), Universitat Autònoma de Barcelona, Badalona, Spain
26Hematology Service, ICO-Hospital Germans Trias i Pujol, Institut de Recerca contra la Leucèmia Josep Carreras (IJC), Universitat Autònoma de Barcelona, Badalona, Spain

Background

The CPSS-Mol scoring system is specific to chronic myelomonocytic leukemia (CMML) and identifies 4 risk groups by integrating various risk factors, including the percentage of bone marrow (BM) blasts, white blood cell count (WBC), transfusion dependency, the presence of cytogenetic abnormalities and mutations in ASXL1, NRAS, RUNX1 and SETBP1. Recently, the IPSS-M score has been developed for patients with myelodysplastic syndrome (MDS), classifying patients into 6 risk groups. This index considers the presence of mutations in 31 genes, among other variables. IPSS-M was developed from a series of 2,957 patients, primarily MDS, but also included 272 cases with the myelodysplastic variant of CMML (MD-CMML). The aim of this study was to evaluate the utility of the IPSS-M in CMML, compare both scoring systems, and explore their applicability in the myelodysplastic (MD-CMML) and myeloproliferative (MP-CMML) variants of the disease.

Methods

Clinical and molecular data were collected retrospectively in a series of patients from the Spanish Registry of MDS and the Munich Leukemia Laboratory, diagnosed with CMML according to the 2022 WHO classification. CPSS-Mol and IPSS-M scores were calculated. Overall survival (OS) was assessed using the Kaplan-Meier method and comparisons were performed with the log-rank test. Cumulative incidence of progression to acute myeloid leukemia (AML) was analyzed by competing risks. The discriminative ability of the CPSS-Mol and IPSS-M models was evaluated using the concordance index (Harrell's c-index).

Results

A total of 449 cases of CMML were included with a median follow-up of 1.91 (0.07-15.35) years. Median age at diagnosis was 73 years old (range 27-95) and 69.0% (n=310) were men. According to 2022 WHO, 80.4% (n=361) of patients were classified as CMML-1 and 19.6% (n=88) as CMML-2. As per the FAB classification, 66.6% (n=299) of cases were classified as MD-CMML and 33.4% (n=150) as MP-CMML. Regarding peripheral blood counts, median values were: Hb 11.8g/dL (4.9 – 17.8), WBC 9.00x109/L (2.40 – 93.67), ANC 4.11x109/L (0.10 – 54.73), monocytes 1.80x109/L (0.52 – 36.60), monocyte percentage 21.9% (10.0 – 65.0) and platelets 130 x109/L (6 – 1377). Median percentage of blasts and promonocytes in BM was 4.0% (0.0 -19.0). Overall, median OS was 4.52 years (3.99-6.05) and 17.1% (n=77) of patients progressed to AML, with an AML incidence at 5 years of 21.0% (17.0%-26.0%).

According to CMML specific cytogenetic risk classification, 87.1% (n=391) were classified as low risk (376 cases with normal karyotype and 15 with isolated –Y), 6.0% (n=27) as intermediate risk, and 6.9% (n=31) as high risk (14 cases with +8, 11 with -7/del(7q), and 6 with complex karyotype). Most patients (93.5%, n=420) presented with at least one mutation according to targeted NGS study. Most frequently (>10%) mutated genes were TET2 (63.9%), ASXL1 (37.0%), SRSF2 (36.7%), RUNX1 (16.3%), CBL (13.1%), NRAS (12.0%) and ZRSR2 (10.2%).

After applying the CPSS-Mol, patients were classified into 4 risk groups with significantly different OS and AML incidence at 3 years (p<0.001): low (OS 79%, AML 4%), intermediate-1 (OS 76%, AML 7%), intermediate-2 (OS 56%, AML 19%), and high (OS 40%, AML 34%). Using the IPSS-M, they were categorized into 6 groups with significantly different OS and AML incidence at 3 years (p<0.001): very low (OS 91%, AML 2%), low (OS 68%, AML 13%), moderate-low (OS 68%, AML 20%), moderate-high (OS 50%, AML 15%), high (OS 42%, AML 24%), and very high (OS 24%, AML 43%).

After grouping CPSS-Mol into 2 risk groups and IPSS-M into 3 risk groups, both scoring systems showed a similar discriminative capacity, with the IPSS-M being superior; with a c-index for OS of 0.608 for CPSS-Mol and 0.647 for IPSS-M; and a c-index for AML progression risk of 0.576 for CPSS-Mol and 0.614 for IPSS-M. Then we assessed the utility of the scores in the MD and MP variants. Both were effective in MD-CMML (c-index for OS of 0.616 for CPSS-Mol and 0.663 for IPSS-M; c-index for AML incidence of 0.555 for CPSS-Mol and 0.623 for IPSS-M), and in MP-CMML (c-index for OS of 0.509 for CPSS-Mol and 0.573 for IPSS-M; c-index for AML incidence could not confidently be assessed due to the low number of events in the low risk groups). Both scores showed better discriminative capacity among MD-CMML.

Conclusions

The IPSS-M is applicable in patients with CMML, in both MD-CMML and MP-CMML, and shows a superior discriminative capacity compared to CPSS-Mol.

Disclosures: Díaz-Beyá: BMS: Consultancy; Abbvie: Consultancy; Takeda: Consultancy; Novartis: Consultancy; Jazz Pharmaceuticals: Consultancy. Ramil López: Johnson & Johnson's: Other: Travel grant to attend conference; Abbvie: Other: Travel grant to attend conference; Astellas: Other: Travel grant to attend conference. Tormo: SOBI: Other: Data Safety Monitoring Board; Janssen, AbbVie, Jazz: Other: Travel grant for attending meetings; AbbVie, Gilead, Pfizer, Astellas, BMS: Honoraria. Collado: Janssen-Cilag and S.A.: Other: support for attending meetings. Diez-Campelo: Gilead: Other: Travel reimbursement; BMS/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Advisory board fees; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; BLUEPRINT MEDICINES: Consultancy, Membership on an entity's Board of Directors or advisory committees; AGIOS: Consultancy, Membership on an entity's Board of Directors or advisory committees; KEROS: Honoraria, Membership on an entity's Board of Directors or advisory committees; CURIS: Membership on an entity's Board of Directors or advisory committees; ASTEX/OTSUKA: Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL TO MEETINGS; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; HEMAVAN: Membership on an entity's Board of Directors or advisory committees; SYROS: Membership on an entity's Board of Directors or advisory committees. Zamora: Celgene/BMS, Incyte, Novartis: Other: Lurdes Zamora reports grants and personal fees from Celgene/BMS, Incyte, and Novartis outside the submitted work.. Xicoy: BMS: Honoraria.

*signifies non-member of ASH