Abstract Introduction Bone marrow involvement is a rare occurrence in patients with advanced breast cancer (ABC), and the prognosis in this context is generally poor. Prompt initiation of treatment to improve the patient's hematological status is crucial. However, this condition is often excluded from clinical trials, making it challenging to determine the effectiveness of new drugs. Limited data and evidence are available to guide treatment decisions, but guidelines recommend starting with chemotherapy for the need of a rapid response. This study aims to analyze the real-world efficacy of cyclin-dependent kinase inhibitors (CDKis) in HR+/HER2- ABC with bone marrow infiltration. Methods Retrospective multicenter cohort study including HR+/HER2- ABC patients from public and private facilities in Argentina. Patients with confirmed bone marrow involvement (blood smear or histological biopsy analysis) and treated with CDKi were eligible. Bone marrow response was defined as an increase in at least one of the previously abnormal blood series to Hb >10.0, platelets >100,000, and leukocytes >4,000. Results A total of 22 patients from different medical centers in Argentina were included. The median age was 55.5 (IQR 46.25-65). Histological confirmation of bone marrow involvement was reported in 81.8% (18) of patients. Among them, 54.5% (12) had initial diagnosis at an early stage, and 13.6% (3) experienced relapse during or within 1 year of completing adjuvant hormonal treatment. Bone-only metastasis was observed in 50% (11) of patients, while the remaining 50% (11) had both visceral and bone disease. Anemia, thrombocytopenia, and leukopenia were present in 95.5% (21), 90.9% (20), and 40.9% (9) of patients, respectively. In 68.2% (15) of patients, bone marrow involvement was detected at the first-line treatment setting. The selected CDKis were palbociclib in 40.9% (9) of patients, ribociclib in 31.8% (7), and abemaciclib in 27.3% (6). The bone marrow response rate was 68.2% (15), with a median of 2 cycles (range 1-5) required for a response. Dose reduction was necessary in 31.8% (7) of patients. Discussion Managing patients with uncommon sites of metastasis, such as bone marrow, poses significant challenges for oncologists. Bone marrow infiltration leads to hematopoietic alterations that adversely affect the quality of life, resulting in increased risk of infections, bleeding, and other comorbidities with fatal consequences. While chemotherapy is the standard treatment in such cases, our study demonstrates that CDKis are a safe and effective option for managing these complications. Conclusion The findings of this study support the evaluation of CDKis as a standard treatment for HR+/HER2- ABC patients. Our results are in line with the recently published phase 2 clinical trial RIGHT CHOICE, which showed a prolonged progression free survival in patients treated with ribociclib and HT with HR+/HE2- ABC and visceral crisis. Citation Format: Alexis Ostinelli, Pablo Mandó, Carolina Almada, Melina Winocur, M. Agustina Ipiña, Viviana Paez, Silvia Aparicio, Sergio Rivero, Federico Waisberg, Laura Sabina Lapuchesky, Cristian Micheri, M. Belen Montenegro, Cristina Rusz Maidana, Carolina Reinhardt, Evelina Rovera, Gonzalo Gómez Abuin, Santiago Bella, Florencia Perazzo, Adrian Nervo, Andrea Aguilar, Matías Chacón, Victoria Costanzo, Valeria Caceres, Jorge Nadal. Cyclin-dependent kinase inhibitor plus endocrine therapy in HR+/HER2- invasive breast cancer with bone marrow and pancytopenia: a new standard of care? Collaborative multicentric Argentinean real-world study (SUMA-02) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-16-07.