Prognostic factors and outcomes in patients with hematological malignancies developing therapy-related acute myeloid leukemia.

Abstract

e24037 Background: Patients (pts) with chronic lymphocytic leukemia (CLL), lymphomas (L), and multiple myeloma (MM) are at increased risk of second primary hematological malignancy (SPHM) due to reduced immune surveillance and prior cancer therapies while risk factors and incidence are largely unknown. Methods: We conducted a retrospective chart review of pts with MM, CLL, and L who developed therapy-related acute myeloid leukemia (t-AML) at Ohio State University from 2010-2022. Data collected included patient demographics, initial primary malignancy characteristics and directed therapies, and t-AML characteristics. Results: We identified 34 pts with t-AML with 9 pts with primary MM, 12 pts with CLL, and 13 pts with L prior to SPHM. The median age at AML diagnosis was 68 years (y). The median time to SPHM was shorter for CLL pts (26.3 mo; range: 12.4-73 mo), compared to MM (73 mo; range: 27-103 mo) or L (195.9 mo; range: 79-305 mo). Autologous stem cell transplant was performed in 7/9 (77.8%) MM pts and in 4/13 (30.8%) L pts. One L pt underwent allogeneic stem cell transplant. 6/12 (50%) pts with CLL received chemotherapy with fludarabine and/or cyclophosphamide. All pts with MM were exposed to lenalidomide (median exposure time = 32.5 mo). T-AML was preceded by myelodysplastic syndrome (MDS) in 4/9 (44.4%) pts with MM, in 5/12 (41.7%) pts with CLL, and 10/13 (76.9%) pts with L. IPSS-R scores were > 4.5 (high to very high risk) in all except 3 pts, with similar scores across the groups (MM range: 4.5-6; CLL range: 2-8.5; L range: 1.5-8.5). Time to progression to AML from MDS was short (median MM: 12.2 mo; CLL: 5.1 mo; L: 6.4 mo). Most cases of t-AML (26/34, 76.5%) were classified as adverse risk per the ELN 2022 classification. NPM1 and FLT3 mutations were found only in pts with CLL (4/11, 36.4%, and 2/11, 18.2%); IDH1/2 mutations were rare (4/34, 11.8%), while TP53 mutations were prevalent (AML-L: 9/12, 75%; AML-MM: 4/8, 50%; AML-CLL: 4/10, 40%). Complex karyotypes and/or deletion of chromosomes 5 or 7 were present in 25/32 (78.1%) pts with available data. The median follow-up from primary malignancy diagnosis was 6.4 y for MM, 5.1 y for CLL, and 6.7 y for L. Cytarabine + daunorubicin was used in 1/13 (7.7%) t-AML pts with L, 5/9 (55.5%) pts with MM, and 4/12 (33.3%) pts with CLL. Hypomethylating agent therapy ± venetoclax was the most common alternative across all groups. Overall survival (OS) significantly differed among the groups (L: 81 days, 95% CI:17-144.4; MM: 191 days, 95% CI:0-483.2; CLL: 347 days, 95% CI:82.2-611.8, log-rank p = 0.02). The presence of NPM1 mutations and adverse ELN risk also correlated with OS. Conclusions: In summary, pts with MM, CLL, and L who developed t-AML have a poor prognosis with median OS of less than 1 y. Their disease showed high-risk features, including adverse ELN2022 scores, high prevalence of TP53 mutations and complex karyotype.