Integration of Geriatric Assessment and Genetic Profile Facilitates Personalized Treatment Selection and Follow-up in Old Patients with Newly Diagnosed Acute Myeloid Leukemia
Authors: Lancho Lavilla Pilar , Lopez-Esteban Miguel , Ortiz-Alonso Javier , Fajardo-Tórtola Gracia , Font Lopez Patricia , Gomez Llobell Marina , Serra Resach Jose Antonio , Perez-Corral Ana , Regalado Artamendi Isabel , Ballesteros Andrés Mónica , Martinez-Laperche Carolina , Figaredo Garcia-Mina Gloria , Fernández González Raquel , Jiménez Carlos , Conde Royo Diego , Pascual Izquierdo Cristina , Vidán María Teresa , García-Sanz Ramon , Rodriguez Macias Gabriela 
Published: December 2024

INTRODUCTION:
Acute myeloid leukemia (AML) is the most common acute leukemia in adults, with a median age at diagnosis of 68y. The development of new therapies is making treatment decisions more complex, especially for older patients(pts), ranging from intensive chemotherapy (IQ) aimed at cure, to gentler less toxic options for chronic management. Thus, the most appropriate treatment for elderly pts requires integrating biological characteristics of leukemia with patient's clinical condition, anticipated tolerance to treatment and preference. A complete geriatric assessment (GA) could be the best tool for providing adequate treatment for each patient. So, we designed a prospective study to address this question.
Our aim is to assess the utility of GA, geriatric intervention, and Hematology/Geriatric joint follow up in old pts newly diagnosed with AML or Myelodysplastic Syndrome (MDS)/AML.
METHODS
From October 2023 to July 2024 pts aged ≥65y with newly diagnosed AML or MDS /AML according to 2022 International Consensus Classification in our hospital were included. After AML diagnosis and genetic characterization, they received a GA with the domains recommended by HematoGeriatrics Spanish Group: functionality, mood (PHQ9), subjective health status, polypharmacy, nutrition (MNA-SF), physical performance (SPPB, gait speed), cognition (MMSE), comorbidity (CIRS), social support, frailty (Fried, FI-CGA-10). Risk of chemotherapy toxicity was evaluated using CARG score, and traditional evaluations included ECOG and HCT-CI. Treatment was decided based on GA, genetics and patient preference. Joint Hematology Geriatric follow up was offered to all. One month after treatment initiation functionality, nutrition, mood, physical performance and quality of life were assessed.
RESULTS
In this interim analysis, 27 pts with AML (22) or MDS/AML (5) were included. Median age was 75y (range 65-89): 16 were&gt;70y (59%) and 7 were &gt;80y (26%). Most (89%) were Caucasian and 10 (37%) were male. Regarding clinical characteristics,18 (67%) were de novo AML, 8 (30%) had a prior hematologic disease and 6 (22%) had therapy related AML. At diagnosis median (range) of leucocytes, platelets and blasts in bone marrow was 9·109/L (2.1-39), 59·109/L (84-22) and 34% (22-67) respectively. According to cytogenetic risk 9 (33%) were classified as adverse and 13 (48%) as intermediate. TP53 was mutated in 5 (18.5%) and NPM1 in 5 (18.5%, 2 concomitant FLT3 mutated). ELN-22 risk was favorable in 3 (11%), intermediate in 3 (11%), adverse in 18 (67%) and not available in 3 (11%). GA summary data was: 65% polypharmacy, 10% dependent on some basic Activities of Daily Living (ADLs), 10% cognitive impairment, and 20% mood disorders. 20% had an ECOG ≥2, but 85% were pre-frail or frail according to Fried and 50% according to FI-CGA-10. Nutritional alterations were present in 35% and 65% had an intermediate or high risk of toxicity.
Selected 1st line treatment was IQ in 4 (15%) pts, hypomethylating agent (HMA) + venetoclax (VEN) in 19 (70%), azacitidine in 2 (7%) and direct allogeneic transplant in 1 (3%). One received supportive care. Main geriatric interventions included high risk drug withdrawal, adjustment of other pathologies and nutritional intervention.
One month after treatment initiation 60% of pts had functional impairment (non severe dependency) and 40% had mood disorders. There were no additional pts with impaired physical performance or nutrition. Only 30% rated their health status below 60%.
With a median follow up of 3.4 months (range 0.5-10) 20 pts remain alive in treatment. Response could be evaluated in 17. Patients treated with HMA + VEN,10 achieved complete response (CR), 2 aplasia without blasts and 3 partial response. Of those with a CR, 2 later progressed and died. Among pts eligible for IQ, 2 died before completing it, 1 achieved CR, 1 is ongoing. There were 7 deaths (1 supportive care, 2 infection, 2 AML, 1 CNS hemorrhage, 1 pulmonary embolism). It is early to provide survival data.
CONCLUSIONS
Geriatric assessment improves characterization of older AML patients and identifies individual vulnerability, facilitating intervention. Joint follow up allows personalized treatment selection for a greater number of patients. Preliminary results on functionality and quality of life need to be confirmed with a larger number and longer follow up and could identify the most objective tools for GA best adapted to older AML patients.